Tech Guide Pt Scint

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Parathyroid Scintigraphy

A Technologists Guide

European Association of Nuclear Medici

ne


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Contributors

Nish Fernando

Chie Technologist

Department o Nuclear Medicine

St. Bartholomews Hospital, London, UK

Dr. Eli Hindi, MD, PhD

Service de Mdecine NuclaireHpital Saint-Antoine, Paris, France

Sue Huggett

Senior University Teacher

Department o Radiography

City University, London, United Kingdom

Jos Pires Jorge

Proesseur HES-S2

Ecole Cantonale Vaudoise de Techniciens enRadiologie Mdicale (TRM)

Lausanne, Switzerland

Regis Lecoultre

Proesseur HES-S2

Ecole Cantonale Vaudoise de Techniciens en

Radiologie Mdicale (TRM)

Lausanne, Switzerland

Sylviane Prvot

Chair, EANM Technologist Committee

Chie Technologist

Service de Mdecine Nuclaire

Centre Georges-Franois Leclerc, Dijon, France

Domenico Rubello*, MDDirector

Nuclear Medicine Service - PET Unit

S. Maria della Misericordia Hospital

Istituto Oncologico Veneto (IOV), Rovigo, Italy

Audrey Taylor

Chie Technologist

Department o Nuclear Medicine

Guys and St. Thomas Hospital, London, UK

Linda Tutty

Senior Radiographer

St. Jamess Hospital

Dublin, Ireland

* Domenico Rubello, MD

is coordinator of the National Study Group on parathyroid scintigraphy of AIMN (Italian Association of Nuclear

Medicine) and is responsible for developing study programmes on minimally invasive radioguided surgery in patients

with hyperparathyroidism for GISCRIS (Italian Study Group on Radioguided Surgery and Immunoscintigraphy)

Acknowledgement for the photo:

P. Lind, Department of Nuclear Medicine, LKH Klagenfurt, Austria


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Contents

Foreword 4

Sylviane Prvot

Introduction 5

Sue Huggett

Chapter 1 Applications o parathyroid imaging 612

Eli Hindi

Chapter 2 Radiopharmaceuticals 1317

Linda Tutty

Chapter 3 Imaging equipment preparation and use 1823

Jos Pires Jorge and Regis Lecoultre

Chapter 4 Patient preparation 2428

Audrey Taylor and Nish Fernando

Chapter 5 Imaging protocols 2932

Nish Fernando and Sue Huggett

Chapter 6 Technical aspects o probe-guided surgery or parathyroid adenomas 3339

Domenico Rubello

Reerences 4043

This booklet was sponsored by an educational grant from Bristol-Myers Squibb Medical Imaging.

The views expressed are those of the authors and not necessarily of Bristol-Myers Squibb Medical

Imaging.


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ForewordSylviane Prvot

Today the notion o competence is at the

heart o proessional development. Technol-

ogists specic proessional skills o working

eciently and knowledgeably are essential

to ensure high-quality practice in nuclear

medicine departments.

Since they were ormed, the EANM Tech-

nologist Committee and Sub-committee onEducation have devoted themselves to the

improvement o nuclear medicine technolo-

gists (NMTs) proessional skills.

Publications that will assist in the setting o

high standards or NMTs work throughout

Europe have been developed. A series o bro-

chures, technologists guides, was planned in

early 2004. The rst o these was dedicated tomyocardial perusion imaging and the current

volume, the second in the planned series, ad-

dresses parathyroid imaging.

Renowned authors with expertise in the eld

have been selected to provide an inormative

and truly comprehensive tool or technolo-

gists that will serve as a reerence and improve

the quality o daily practice.

I am grateul or the hard work o all the con-

tributors, who have played a key role in ensur-

ing the high scientic content and educational

value o this booklet. Many thanks are due to

Sue Huggett, who coordinated the project,

to the members o the EANM Technologist

Sub-committee on Education and particularly

to Bristol-Myers Squibb Imaging or their con-

dence and generous sponsorship.

Eorts to image the parathyroid gland date

back many years. I hope this brochure will be

useul to technologists in the management

o patients with hyperparathyroidism and will

benet these patients by optimising care and

welare.

Sylviane Prvot

Chair, EANM Technologist Committee


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IntroductionSue Huggett

The rst publication o the EANM Technolo-

gist Committee sponsored by Bristol Myers

Squibb in 2004 was a book on myocardial

perusion imaging or technologists. We

are very grateul that they have sponsored

us again this year to produce this book on

parathyroid imaging, the second book in

what we hope will be a series.

We hope that we have combined the theory

and rationale o imaging with the practicalities

o patient care and equipment use. I think that

certain things I wrote or the last book bear re-

peating, and so I will do so here or the benet

o those or whom this is their rst book.

Knowledge o imaging theory provides a deeper

understanding o the techniques that is satisy-ing or the technologist and can orm the basis

or wise decision making. It also allows the tech-

nologist to communicate accurate inormation

to patients, their carers and other sta. Patient

care is always paramount, and being able to

explain why certain oods must be avoided or

why it is necessary to lie in awkward positions

improves compliance as well as satisaction.

Awareness o the rationales or using certain

strategies is needed in order to know when

and how various protocol variations should be

applied, in acquisition or analysis, e.g. or the

patient who cannot lie fat or long enough

or subtraction and may need to be imaged

with another protocol or when we may need

a dierent lter i the total counts are low.

Protocols will vary between departments,

even within the broader terms o the EANM

Guidelines. This booklet is not meant to sup-

plant these protocols but will hopeully sup-

plement and explain the rationales behind

them, thereby leading to more thoughtul

working practices.

The authors are indebted to a number osources or inormation, not least local proto-

cols, and reerences have been given where

original authors are identiable. We apolo-

gise i we have inadvertently used material

or which credit should have been, but was

not, given.

We hope that this booklet will provide help-

ul inormation as and when it is needed sothat the integration o theory and practice is

enabled and encouraged.


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Applications o parathyroid imagingEli Hindi

Primary hyperparathyroidism

Primary hyperparathyroidism (pHPT) is a

surgically correctable disease with the third

highest incidence o all endocrine disorders

ater diabetes mellitus and hyperthyroidism

(Al Zahrani and Levine 1997). Through their

secretion o parathyroid hormone (PTH), the

two pairs o parathyroid glands, located in the

neck posterior to the thyroid gland, regulateserum calcium concentration and bone me-

tabolism. PTH promotes the release o calcium

rom bone, increases absorption o calcium

rom the intestine and increases reabsorp-

tion o calcium in the renal tubules. In turn,

the serum calcium concentration regulates

PTH secretion, a mechanism mediated via a

calcium-sensing receptor on the surace o

the parathyroid cells. pHPT is caused by thesecretion o excessive amounts o PTH by

one or more enlarged diseased parathyroid

gland(s). Patients with pHPT may suer rom

renal stones, osteoporosis, gastro-intestinal

symptoms, cardiovascular disease, muscle

weakness and atigue, and neuropsychologi-

cal disorders. The highest prevalence o the

disease is ound in post-menopausal women.

A prevalence o 2% was ound by screening

post-menopausal women (Lundgren).

In the past, pHPT was characterised by severe

skeletal and renal complications and apparent

mortality. This may still be the case in some

developing countries. The introduction o

calcium auto-analysers in the early 1970s

led to changes in the incidence o pHPT and

deeply modied the clinical spectrum o the

disease at diagnosis (Heath et al. 1980). Most

new cases are now biologically mild without

overt symptoms (Al Zahrani and Levine 1997).

Parathyroidectomy is the only curative treat-

ment or pHPT. In the recent guidelines o the

US National Institute o Health (NIH), surgery

is recommended or all young individuals and

or all patients with overt symptoms (Bilezikianet al. 2002). For patients who are asymptom-

atic and are 50 years old or older, surgery is

recommended i any o the ollowing signs

are present: serum calcium greater than 10

mg/l above the upper limits o normal; 24-h

total urine calcium excretion o more than 400

mg; reduction in creatinine clearance by more

than 30% compared with age-matched per-

sons; bone density more than 2.5 SDs belowpeak bone mass: T score < -2.5. Surgery is also

recommended when medical surveillance

is either not desirable or not possible. Ater

complete baseline evaluation, patients who

are not operated on need to be monitored

twice yearly or serum calcium concentration

and yearly or creatinine concentration; it is

also recommended that bone mass measure-

ments are obtained on a yearly basis (Bilezikian

et al. 2002). Some authors recommend para-

thyroidectomy or all patients with a secure

diagnosis o pHPT (Utiger 1999).

Successul parathyroidectomy depends on

recognition and excision o all hyperunc-

tioning parathyroid glands. pHPT is typically

caused by a solitary parathyroid adenoma, less


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Chapter 1: Applications of parathyroid imaging

requently (about 15% o cases) by multiple

parathyroid gland disease (MGD) and rarely

(about 1% o cases) by parathyroid carcino-

ma. Patients with MGD have either double

adenomas or hyperplasia o three or all our

parathyroid glands. Most cases o MGD are

sporadic, while a small number are associated

with hereditary disorders such as multiple en-

docrine neoplasia type 1 or type 2a or amilialhyperparathyroidism (Marx et al. 2002). Con-

ventional surgery consists in routine bilateral

exploration with identication o all our para-

thyroid glands.

Imaging is mandatory beore reoperation

For several decades, preoperative imaging was

not used beore rst-time surgery. Unguided

bilateral exploration, dissecting all potentialsites in the neck, achieved cure in 9095% o

patients (Russell and Edis 1982). The two main

reasons or ailed surgery are ectopic glands

(retro-oesophageal, mediastinal, intrathyroid,

in the sheath o the carotid artery, or unde-

scended) and undetected MGD (Levin and

Clark 1989). Repeat surgery is associated with a

dramatic reduction in the success rate and an

increase in surgical complications. Imaging is

thereore mandatory beore reoperation (Sosa

et al. 1998). 99mTc-sestamibi scanning (Coakley

et al. 1989) has been established as the imag-

ing method o choice in reoperation o persis-

tent or recurrent hyperparathyroidism (Weber

et al. 1993). In these patients it is necessary to

have all inormation concerning the rst inter-

vention, including the number and location o

parathyroid glands that have been seen by the

surgeon and the size and histology o resected

glands. Whichever 99mTc-sestamibi scanning

protocol is used, it is necessary to provide the

surgeon with the best anatomical inormation

by using both anterior and lateral (or oblique)

views o the neck, and SPECT whenever use-

ul, especially or a mediastinal ocus. It is the

authors opinion that99m

Tc-sestamibi resultsshould be conrmed with a second imaging

technique (usually ultrasound or a neck ocus

and CT or MRI or a mediastinal image) beore

proceeding to reoperation.

Scanning with 99mTc-sestamibi is increasingly

ordered on a routine basis or rst-time

parathyroidectomy

The rst exploration is the best time to curehyperparathyroidism. Most surgeons would

now appreciate having inormation concern-

ing whereabouts in the neck to start dissec-

tion and the possibility o ectopic parathyroid

glands (Sosa et al. 1998; Liu et al. 2005). When

the rare cases (2-5%) o ectopic parathyroid

tumours are recognised preoperatively, the

success o bilateral surgery can now reach

very close to 100% (Hindi et al. 1997). In the

case o a mediastinal gland, the surgeon can

proceed directly with rst-intention thoracos-

copy, avoiding unnecessary initial extensive

neck surgery in the search or the elusive

gland (Liu et al. 2005). Preoperative imaging

would also shorten the duration o bilateral

surgery (Hindi et al. 1997). By allowing the

surgeon to nd the oending gland earlier in


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the operation, the time necessary or rozen

section examination can be used by the sur-

geon or inspection o the other parathyroid

glands, also reducing surgeon anxiety.

Important points to know when proceeding

with parathyroid imaging

Imaging is not or diagnosis. The increase

in plasma levels o calcium (normal value88105 mg/l) and PTH (normal value 1058

ng/l) establishes the diagnosis.

Imaging does not identiy normal parathy-

roid glands, which are too small (2050 mg)

to be seen.

Imaging should detect abnormal para-

thyroid(s) and indicate the approximate sizeand the precise relationship to the thyroid

(the level o the thyroid at which the para-

thyroid lesion is seen on the anterior view;

and whether it is proximal to the thyroid or

deeper in the neck on the lateral or oblique

view or SPECT) (Fig. 1).

Imaging should identiy ectopic glands (add

SPECT in cases o a mediastinal ocus, and

ask or additional CT or MRI or conrmation

and anatomical landmarks) (Fig. 2).

Imaging should be able to dierentiate pa-

tients with a single adenoma rom those

with MGD (Fig. 3).

Imaging should identiy thyroid nodules

that may require concurrent surgical re-

section.

The choice o imaging technique

The most common preoperative localisation

methods are radionuclide scintigraphy and

ultrasound. As stated beore, the two main

reasons or ailed surgery are ectopic glands

and undetected MGD (Levin and Clark 1989).Because high-resolution ultrasound would,

even in skilled hands, ail to detect the major-

ity o these cases, it is not optimal or preop-

erative imaging as a single technique. In the

study by Haber et al. (2002), ultrasound missed

six o eight ectopic glands and ve o six cases

o MGD. Ultrasound may, however, be useul

in combination with 99mTc-sestamibi imaging

(Rubello et al. 2003).

99mTc-sestamibi scanning is now considered

the most sensitive imaging technique in pa-

tients with pHPT (Giordano et al. 2001; Mullan

2004). Whatever the protocol used, 99mTc-ses-

tamibi scanning will usually meet the require-

ment o detecting ectopic glands (all eight

were detected in the study by Haber et al.).

With regard to the recognition o MGD, how-

ever, the protocol in use will determine the

sensitivity. When 99mTc-sestamibi is used as a

single tracer with planar imaging at two time

points -- the dual-phase (or washout) method

the sensitivity or primary hyperplasia is very

low (Tailleer et al. 1992; Martin et al. 1996). Bet-

ter results can be obtained by adding SPECT.

Subtraction scanning, using either

123

I (Borley


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et al. 1996; Hindi et al. 2000; Mullan 200)

or 99mTc-pertechnetate (Rubello et al. 2003)

in addition to 99mTc-sestamibi, improves the

sensitivity or hyperplastic glands. One di-

culty with subtraction imaging is keeping the

patient still or the time necessary to scan the

thyroid, to inject 99mTc-sestamibi and to record

images o this second tracer. Simultaneous

recording o123

I and99m

Tc-sestamibi can be asimple answer to these diculties. It prevents

arteacts on subtraction images due to pa-

tient motion, and shortens the imaging time

(Hindi et al. 1998; Mullan 2004).

Preoperative imaging has opened a new era

o minimally invasive parathyroid surgery

Conventional bilateral exploration is still

considered the gold standard in parathyroidsurgery. However, the introduction o99mTc-

sestamibi scanning, the availability o intra-

operative adjuncts such as the gamma probe

and intraoperative monitoring o PTH to help

detect MGD have challenged the dogma o

routine bilateral exploration. When preopera-

tive imaging points to a single well-dened

ocus, unequivocally suggesting a solitary

adenoma, the surgeon may now choose o-

cussed surgery instead o bilateral exploration.

Focussed excision can be made by open sur-

gery through a mini-incision, possibly under

local anaesthesia, or by video-assisted endo-

scopic surgery under general anaesthesia (Lee

and Inabnet 2005). Compared with patients

who undergo bilateral surgery, those in whom

ocussed parathyroid surgery is successully

completed enjoy a shorter operation time,

the possibility o local anaesthesia, a better

cosmetic scar, a less painul postoperative

course, less proound postoperative transient

hypocalcaemia and an earlier return to normal

activities. The act that many clinicians now

use a lower threshold or surgery is partly due

to the perception that parathyroid surgery is

easier than in the past (Utiger 1999).

Patients at specic risk o ailure o minimal

surgery are those with unrecognised MGD.

Thereore, when choosing minimal surgery,

the surgeon is committed to distinguishing

cases o MGD either preoperatively, through

an appropriate imaging protocol, or by intra-

operative monitoring o PTH plasma levels, or

by a combination o both. The true sensitivityo intraoperative PTH or MGD is still under

debate. What raises concern is that studies

relying solely on intraoperative measurements

report a low percentage o MGD, only 3% (Mo-

linari et al. 1996), which is three to our times

lower than is generally observed during rou-

tine bilateral surgery. Whether this will lead to

higher rates o late recurrence is not known. It

is thus important that imaging methods used

to select patients or ocussed surgery have a

high sensitivity or detecting MGD.

In this new era o ocussed operations, the

success o parathyroid surgery depends not

only on an experienced surgeon but also on

excellent interpretation o images. A localisa-

tion study with high accuracy is mandatory to


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avoid conversion o the surgery to a bilateral

exploration under general anaesthesia ater

minimal surgery has been started. It is impor-

tant to avoid conusion with a thyroid nod-

ule, and precise anatomical description is also

important. With enlargement and increased

density, superior parathyroid adenomas can

become pendulous and descend posteriorly.

A lateral view (or an oblique view or SPECT)should indicate whether the adenoma is close

to the thyroid or deeper in the neck (tracheo-

oesophageal groove or retro-oesophageal).

This inormation is useul, because visualisa-

tion through the small incision is restricted.

Moreover, the surgeon may choose a lateral

approach to excise this gland instead o an

anterior approach. To achieve a high sensitiv-

ity in detecting MGD with subtraction tech-niques, the degree o subtraction should be

monitored careully. Progressive incremental

subtraction with real-time display is a good

way to choose the optimal level o subtraction

(residual 99mTc-sestamibi activity in the thyroid

area should not be lower than in surround-

ing neck tissues). Oversubtraction could easily

delete additional oci o activity and in some

patients provide a alse image suggestive o

a single adenoma.

Secondary hyperparathyroidism

Secondary hyperparathyroidism is a common

complication in patients with chronic renal

ailure. Hypocalcaemia, accumulation o phos-

phate and a decrease in the active orm o

vitamin D lead to increased secretion o PTH.

With chronic stimulation, hyperplasia o para-

thyroid glands accelerates and may develop

into autonomous adenomas. The extent o

parathyroid growth then becomes a major

determinant o PTH hypersecretion. Second-

ary hyperparathyroidism leads to renal bone

disease, the development o sot tissue calci-

cations, vascular calcications and increased

cardiovascular risk, among other complica-tions. When medical therapy ails, surgery

becomes necessary. Surgery can be either

subtotal parathyroidectomy, with resection

o three glands and partial resection o the

ourth gland, or total resection with grating

o some parathyroid tissue into the sot tissues

o the orearm in order to avoid permanent

hypoparathyroidism.

Preoperative imaging

Surgery o secondary hyperparathyroidism

requires routine bilateral identication o all

parathyroid tissue. Moreover, early studies

based on single-tracer 99mTc-sestamibi scan-

ning have reported a very low sensitivity

o about 050% in detecting hyperplastic

glands. Ineciency o single-tracer techniques

both in secondary hyperparathyroidism and

in primary hyperplasia is possibly due to more

rapid washout o tracer rom hyperplastic

glands than rom parathyroid adenomas. For

those reasons, preoperative imaging has not

yet gained wide acceptance among surgeons.

Dual-tracer subtraction imaging, planar or

SPECT, provides substantial improvement in

the rate o detection o hyperplastic glands in


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patients with renal ailure (Hindi et al. 1999;

Peri et al. 2005)

What inormation can be obtained?

The preoperative map may acilitate rec-

ognition o the position o aberrant para-

thyroid glands, also reducing the extent o

dissection (Hindi et al. 1999).

Parathyroid glands with major ectopia

would be missed without preoperative

imaging.

Although the usual number o parathyroid

glands is our, some individuals (about 10%)

have a supernumerary th gland (Aker-

strm et al. 1984). When this inormation is

provided by preoperative imaging, it mayprevent surgical ailure or late recurrence

(Hindi et al. 1999).

Imaging ndings in patients with persistent

or recurrent secondary hyperparathyroidism

Immediate ailure and delayed recurrence are

not unusual, occurring in 1030% o patients.

Imaging is mandatory beore reoperation.

Knowledge o all details concerning the initial

intervention is necessary or interpretation. As

with primary hyperparathyroidism, we recom-

mend that lesions seen on the 99mTc-sestamibi

scan be matched with a second radiological

technique (ultrasound or MRI) or conrmation

and identication o anatomical landmarks

beore reoperation.

Some aspects specic to patients reoperated

or secondary hyperparathyroidism need to

be emphasised:

Specic views o the orearm should be

obtained in patients who have had a para-

thyroid grat.

It is not unusual or imaging in these pa-tients to show two oci o activity, one

corresponding to recurrent disease at the

subtotally resected gland (or grated tissue)

and the other corresponding to an ectopic

or th parathyroid, missed at initial inter-

vention (unpublished data).

Figure 1

Parathyroid subtraction scintigraphy, with simul-

taneous acquisition o99mTc-sestamibi and 123I

in a patient with primary hyperparathyroidism.

The anterior view and the lateral view show a

solitary adenoma located at the lower right pole

o the thyroid. At surgery, an adenoma o 1.9 g

was ound at the predicted site.


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1

Figure 2This patient with a previous history o thyroid surgery (right lobectomy) was reerred with a recent

diagnosis o primary hyperparathyroidism. Ultrasound examination suggested the presence o

a parathyroid adenoma at the side o previous thyroid lobectomy, which was a alse-positive

image. The large eld o view 99mTc-sestamibi acquisition shows a mediastinal ocus (arrow).

The suspected ectopic parathyroid was conrmed by MRI (arrow). A mediastinal parathyroid

adenoma o 0.59 g was resected.

Figure 3

Parathyroid 99mTc-sestamibi/123I subtraction scintigraphy in a patient with primary hyperpara-

thyroidism. The computed subtraction images show two sites o preerential 99mTc-sestamibi

uptake: one at the lower third o the let thyroid lobe and the second lateral to the lower pole

o the right thyroid lobe. Two adenomas were excised: a let parathyroid adenoma weighing

2.3 g and a right adenoma weighing 0.07 g.


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1

RadiopharmaceuticalsLinda Tutty

Radiopharmaceuticals used or

parathyroid scintigraphy

Details o the photo peak energy, hal-lie, e-

ective dose and standard dose or radiophar-

maceuticals commonly used or parathyroid

scintigraphy are shown in Table 1.

201Tl-chloride201

Tl-chloride has a physical hal-lie o 73.1 h.Its main photo peak is due to characteristic x-

rays o mercury, which have an energy range

o 6983 keV. In addition, gamma rays are pro-

duced at 167 keV (8%) and 135 keV (2%). The

administered activity is 80 MBq and it is given

intravenously. 201Tl-chloride is taken up by ab-

normal parathyroid tissue and thyroid tissue in

proportion to blood fow.

99mTc-pertechnetate99mTc-pertechnetate has a hal-lie o 6 h and a

gamma energy o 140 keV. 99mTc-pertechnetate is

used to delineate the thyroid gland because unc-

tioning thyroid parenchyma traps it. This image is

then subtracted rom the 201Tl or 99mTc-sestamibi

images, and what remains is potentially a parathy-

roid adenoma. When utilising 201Tl, the adminis-

tered activity is usually 75150 MBq, depending on

the administered radioactivity o201Tl and which o

the two radiopharmaceuticals is administered rst.

I using 99mTc-sestamibi, the amount o pertechne-

tate administered is usually 185370 MBq, because99mTc-sestamibi has a higher total activity in the

thyroid tissue than 201Tl.

99m

Tc-sestamibiThe range o intravenously administered radio-

activity is 185-900 MBq; the typical dose is 740

MBq. This radiotracer localises in both parathyroid

gland and unctioning thyroid tissue, and usually

washes out o normal thyroid tissue more rap-

idly than out o abnormal parathyroid tissue. The

exact mechanism o uptake remains unknown

(Farley 2004). 99mTc-sestamibi uptake depends on

numerous actors, including perusion, cell cycle

phase and unctional activity (Beggs and Hain2005). The nal cellular localisation o99mTc-sesta-

mibi is within the mitochondria. It accumulates in

the mitochondria o many tissues but particularly

in normal cardiac and thyroid cells; it is especially

prominent in overactive parathyroid glands and

is held there preerentially (Farley 2004).

123I-sodium iodide

123I has a hal-lie o 13 h and emits a photonwith an energy o 159 keV. It has been used

particularly with 99mTc-sestamibi as a thyroid-

imaging agent in subtraction studies. The

administered dose, given orally, ranges rom

7.5 to 20 MBq.

99mTc-tetroosmin99mTc-tetroosmin use in parathyroid imaging

is described in the literature (Smith and Oates

2004). Its manuacturers do not license it or

use as a parathyroid scintigraphy agent. 99mTc-

sestamibi and 99mTc-tetroosmin have similar

imaging characteristics (Smith and Oates

2004). The typical dose o administered activ-

ity is 740 MBq.

11

C-methionine11C-methionine has a hal-lie o 20 min. It is


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1

cyclotron produced. Its uptake reects amino

acid refux into stimulated parathyroid tissue

(Otto et al. 2004; Beggs and Hain 2005). Up-

take in infammatory conditions may pose

a problem and should be considered when

interpreting images. The typical radioactivity

dose ranges between 240 and 820 MBq, with

an average intravenous dose o 400 MBq.

18F-FDG18F-FDG has a hal-lie o 110 min and is cy-

clotron produced. 18F-FDG allows glucose

metabolism to be assessed and evaluated

using PET. There is dierential concentra-

tion o FDG in abnormal parathyroid tissue

and this dierence is used to demonstrate

the abnormal gland. FDG also accumulates

in other malignant and benign tissues, andin infamed or inected tissue; this potentially

limits its useulness. The typical intravenous

dose is 400 MBq.

Radiopharmaceutical eatures

Multiple radiopharmaceuticals have been

described or the detection o parathyroid le-

sions. Thallium, sestamibi and tetroosmin are

the three most commonly used (Ahuja et al.

2004). All these agents were originally devel-

oped or cardiac scanning. In the 1980s, 201Tl

was the most commonly used agent, but it

has a longer hal-lie and delivers a higher ra-

diation dose to the patient (Kettle 2002). Con-

sequently, 201Tl is no longer commonly used,

and most recent literature reers to the use o99m

Tc-sestamibi. However, or the subtraction

method it is probable that each radiopharma-

ceutical would provide the same diagnostic

inormation (Kettle 2002).

Subtraction agents

Thyroid-specic imaging with 123I or 99mTc-

pertechnetate may be employed using a sub-

traction method to dierentiate parathyroid

rom thyroid activity (Clark 2005).

The two main agents used or imaging the

thyroid are 123I (sodium iodide) and 99mTc-

pertechnetate. There is a slight preerence or

the use o123I, as it is organied and thereore

provides a stable image. The pertechnetate

washes out rom the thyroid gland with time,

and i there is some delay in imaging there

may be a reduction in the quality o thethyroid image (Kettle 2002). However, both

agents may be aected i the patient is taking

thyroxine or anti-thyroid medications or has

recently received iodine contrast agents.

Thyroid-specic radiopharmaceuticals may

aid delineation o the thyroid parenchyma i

required ater dual-phase imaging. This may

be helpul as a second-line visual subtraction

procedure when no parathyroid adenoma is

visible on dual-phase parathyroid imaging

(Clark 2005).

Activities given or imaging the thyroid

and parathyroid glands are as ollows: 99mTc

pertechnetate, 80 MBq; 123I, 0 MBq; 201Tl,

80 MBq;

99m

Tc-sestamibi, 900 MBq. I a

99m

Tc-


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1

Chapter 2: Radiopharmaceuticals

pertechnetate/99mTc-sestamibi combination

is used then the radiation dose or the com-

bined study is 11.6 mSv. I123I and 201Tl are used,

this rises to 18.3 mSv.

Dual-phase agents99mTc-sestamibi and 99mTc-tetroosmin are com-

monly used agents or dual-phase parathyroid

scintigraphy. The washout technique relies onthe act that while 99mTc-sestamibi and 99mTc-tet-

roosmin are taken up by both the thyroid gland

and the parathyroid at a similar rate, there is a

aster rate o washout rom the thyroid gland.

These tracers localise in the thyroid gland as

well as in parathyroid adenomas. This makes

correlation o the adenoma in relation to the

thyroid gland possible on planar as well as earlySPECT imaging. 99mTc-sestamibi is released rom

the thyroid with a hal-lie o about 30 min but

is usually retained by abnormal parathyroid

glands (Smith and Oates 2004). 99mTc-tetroos-

min may clear more slowly rom the thyroid

gland. This dierential washout improves the

target-to-background ratio so that abnormal

parathyroid tissue should be more visible on

delayed images (Smith and Oates 2004; Clark

2005). However, thyroid adenomas and carcino-

mas can coexist and may retain 99mTc-sestamibi

or 99mTc-tetroosmin, resulting in alse positive

results (Smith and Oates 2004).

99mTc-sestamibi and 99mTc-tetroosmin have

comparable imaging characteristics. Usually,

the choice o imaging agent depends on its

availability and the experience o the nuclear

medicine radiologist.

The dual-phase subtraction method with ad-

junctive thyroid-selective imaging (99mTc or 123I)

may be helpul, or even essential, in patients

with goitres or other conounding underly-

ing thyroid disease, ater thyroid surgery or in

those patients with a palpable mass (Smithand Oates 2004).

PET imaging agents

Use o18F-fuorodeoxyglucose (FDG) positron

emission tomography (PET) and 11C- methio-

nine PET or parathyroid imaging has been de-

scribed (Otto et al. 2004; Beggs and Hain 2005).

Initial studies with PET have shown conficting

results when using FDG as a tracer to image theparathyroid glands (Beggs and Hain 2005; Otto

et al. 2004). It has been shown that 11C-methio-

nine PET holds more promise than FDG PET im-

aging o the parathyroid localisation (Beggs and

Hain 2005). 11C-methionine PET scanning is o

value in cases o primary hyperparathyroidism

in which conventional imaging techniques have

ailed to localise the adenoma beore proceed-

ing to surgery, or in patients in whom surgery

has been perormed but has ailed to correct the

hyperparathyroidism (Beggs and Hain 2005).

Adverse reactions to

radiopharmaceuticals

Table 2 shows side-eects and reactions to

radiopharmaceuticals used or parathyroid

scintigraphy.


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1

Table 1

Radiopharmaceuticals used or parathyroid scintigraphy

201Tl- 99mTc 99mTc 11C 18F

chloride sestamibi tetroosmin methionine fuorodeoxy-

glucose

Photo peak 69-80 (98% 140 140 511 511

energy abundance)

(keV) 135 (2%)

167 (8%)Hal-lie 73.1 hours 6 hours 6 hours 20 min 110 min

Cyclotron Always Always Cyclotron Cyclotron

product available available produced produced

to be (24-month (6-month

ordered shel lie at shel lie at

ready or room 2-8C

use temperature)

Eectivedose adult

(mSv)

18 11 9 2 10

Standard 80 900 900 400 400

dose*(MBq)

*Allowable upper limits o radiotracers may dier rom country to country. Please reer to the

Summary o Product Characteristics in each European country. Doses given here are quoted

rom ARSC, December 1998.


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1

Chapter 2: Radiopharmaceuticals

Table 2

Adverse reactions to radiopharmaceuticals used or parathyroid scintigraphy (as printed in J

Nucl Med 1996;37:185192, 10641067)

Radiopharmaceutical Side-eects, reactions201TI-chloride Fever, erythema, fushing, diuse rash,

pruritis, hypotension99mTc-pertechnetate Chills, nausea, vomiting, diuse rash,

pruritis, hives/urticaria, chest pain,

tightness or heaviness, hypertension,

dizziness, vertigo, headache, diaphoresis,

anaphylaxis

99mTc-sestamibi Nausea, erythema, fushing, diuse rash,

pruritis, seizures, headache, metallic taste,

tingling

123I-Sodium iodide Nausea, vomiting, diuse rash,

pruritus, hives/urticaria, chest pain, tightness

or heaviness, respiratory reaction,tachycardia, syncope or aintness and

headache, tachypnea, parosmia

99mTc-tetroosmin Angina, hypertension, torsades de

pointes (these three probably occurred

because o underlying heart disease);

vomiting, abdominal discomort,

cutaneous allergy, hypotension,

dyspnoea, metallic taste, burning o

mouth, unusual odour, mild leucocytosis

18F-FDG None


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1

Imaging equipment preparation and useJos Pires Jorge and Regis Lecoultre

Quality control procedures that must be

satisactorily perormed beore imaging

Ater acceptance testing, a QC protocol must

be set up in each department and ollowed

in accordance with national guidelines. The

ollowing routine quality control test schedule

is typical:

a) Daily energy peaking

b) Daily food uniormity tests

c) Daily gamma camera sensitivity measure-

ment

d) Weekly linearity and resolution assess-

ment

e) Weekly centre-o-rotation calibration

A routine quality control programme or a

SPECT gamma camera includes quality control

procedures appropriate to planar scintillation

cameras (ad) and specic SPECT quality con-

trols (e). Further, more complex tests should be

undertaken on a less requent basis.

Energy peaking

This quality control procedure consists in

peaking the gamma camera or relevant

energies prior to obtaining food images. It

is mandatory that the energy peaking is un-

dertaken on a daily basis and or each radio-

nuclide used.

Checking the peaking is needed to ascertain

that:

The camera automatic peaking circuitry is

working properly

The shape o the spectrum is correct

The energy peak appears at the correctenergy

There is no accidental contamination o the

gamma camera

It is recommended that the spectra obtained

during peaking tests are recorded.

Daily food uniormity testsAter a successul peaking test it is recom-

mended that a uniormity test is perormed

on a daily basis. Flood elds are acquired and

evaluation o camera uniormity can be made

on a visual assessment. Quantitative param-

eters should also be computed regularly and

recorded in order both to demonstrate sud-

den variations rom normal and to alert the

technologist to progressive deterioration in

the equipment. On cameras that have inter-

changeable uniormity correction maps, it

is vital that one is used that is for the correct

nuclide, accurate and up to date.

Daily gamma camera sensitivity

measurement

A practical means o measuring sensitivity is


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1

Chapter 3: Imaging equipment - preparation and use

by recording the time needed to acquire the

food eld using the known activity. It should

not vary by more than a ew percent rom one

day to another.

Weekly linearity and resolution assessment

Linearity and resolution should be assessed

weekly. This may be done using transmission

phantoms.

Centre o rotation calibration

The centre o rotation measurement deter-

mines the oset between the axis o rotation

o the camera and the centre o the matrix

used or reconstruction, as these do not cor-

respond automatically.

The calibration o the centre o rotation ismade rom the reconstruction o a tomo-

graphic acquisition o a point source placed

slightly oset rom the mechanical centre o

rotation o the camera. A sinogram is ormed

rom the projections and is used to t the

maximum count locations to a sine wave. De-

viations between the actual and tted curves

should not exceed 0.5 pixels.

Collimator

The choice o a collimator or a given study

is mainly determined by the tracer activity.

This will infuence the statistical noise con-

tent o the projection images and the spatial

resolution. The number o counts needs to be

maximised, possibly at the expense o some

resolution and taking into account that in

parathyroid imaging the dierence in tracer

activity between 99mTcO4 (thyroid only) and

any 99mTc-labelled agent (thyroid and parathy-

roid) must be signicant.

Collimators vary with respect to the relative

length and width o the holes. The longer the

hole length, the better the spatial resolution

obtained, but at the expense o a lower countsensitivity. Conversely, a larger hole gives a

better count sensitivity but with a loss o spa-

tial resolution.

When using 201Tl, the available counts are

greatly reduced owing to the long hal-lie

o the isotope and the consequent limited

dose; so traditionally a low-energy general-

purpose collimator is recommended. With99mTc-pertechnetate and 99mTc-labelled agents,

count rate is no longer a major limitation, and

urthermore, the resolution o a high-resolu-

tion collimator decreases less with distance

rom the source than does that o a general-

purpose collimator. Thus a high-resolution

collimator is currently recommended or

SPECT imaging, despite the lower sensitivity.

Although the choice o collimator is crucial, it

should be borne in mind that other technical

aspects play an important role in determining

optimal spatial resolution, such as the matrix

size, the number o angles and the time per

view.

Matrix and zoom actor

The SPECT images (or projections rom the


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0

angles round the patient) create multiple raw

data sets containing the representation o the

data in one projection. Each o these is stored

in the computer in order to process them later

on and extract the inormation.

Matrix

Each projection is collected into a matrix.

These are characterised by the number opicture elements or pixels. Pixels are square

and organised typically in arrays o 66,

128128 or 256256.

In act, the choice o matrix is dependent on

two actors:

a) The resolution: The choice should not de-

grade the intrinsic resolution o the object. Thecommonly accepted rule or SPECT (Groch

and Erwin 2000) is that the pixel size should be

one-third o the ull-width at hal-maximum

(FWHM) resolution o the organ, which will

depend on its distance rom the camera ace.

The spatial resolution o a SPECT system is o

the order o 1825 mm at the centre o rota-

tion (De Puey et al. 2001). Thus a pixel size o

6-8 mm is sucient, which, or a typical large

eld o view camera, leads to a matrix size o

6464.

b) The noise: This is caused by the statistical

fuctuations o radiation decay. The lower the

total counts, the more noise is present and, i

the matrix size is doubled (128 instead o 64),

the number o counts per pixel is reduced by

a actor o 4. 128128 matrices produce ap-

proximately three times more noise on the

image ater reconstruction than do 6 x 6

matrices (Garcia et al. 1990).

The planar images (or static projections) do

not have the reconstruction problem and can

be acquired over longer times so a 256 256

matrix is commonly used.

Zoom actor

The pixel size is dependent on the camera

eld o view (FOV). When a zoom actor o

1.0 is used, the pixel size (mm) is the useul

FOV (UFOV, mm) divided by the number o

pixels in one line. When a zoom actor is used,

the number o pixels per line should rst be

multiplied by this actor beore dividing it intothe FOV.

Example:

Acquisition with matrix 128, zoom 1.0 and

UFOV 400 mm. Pixel size: 400/128=3.125 mm.

The same acquisition with a zoom actor o 1.5.

Pixel size: 400/(1.5128)=2.08 mm.

It is important to check this parameter be-

ore the acquisition, as it is very oten used in

parathyroid imaging, especially i a subtraction

technique is used.

Preerred orbit

Either circular or elliptical orbits can be used

in SPECT imaging (Fig. 1). A circular orbit (Fig.


21/44

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1


With a circular orbit, the camera is distant rom

the body at some angles, causing a reduction

in spatial resolution in these projections. This

will reduce the resolution o the reconstructed

images.

With an elliptical orbit, spatial resolution will be

improved as the camera passes closer to the

body at all angles. Nevertheless, the distance

rom the organ to the detector varies more

signicantly with an elliptical orbit than with

a circular orbit. This may generate arteacts

simulating small photopenic areas when re-

constructing using ltered back projection.

Programmes that allow the camera to learn

and closely ollow the contours o the body

are available and improve resolution, although

at the expense o computing power to modiy

the data beore reconstruction.

The loss o spatial resolution with a circular

orbit has to be oset against the potential ar-

teacts that may be generated by an elliptical

or contoured orbit.

Filtered back projection image

reconstruction: some considerations

The main goal o nuclear medicine parathy-

roid imaging procedures is to identiy the

site o parathyroid hormone production,

usually a single parathyroid adenoma. How-

ever, parathyroid adenomas can be ound in

diverse locations: alongside, beside or within

the thyroid, or in anatomical regions distantrom thyroid, such as high or low in the neck

and mediastinum. The diversity o these ana-

tomical locations makes SPECT a useul tool

in parathyroid imaging.

Furthermore, parathyroid adenomas are small

structures with increased uptake oten close

to normal thyroid activity. The choice o an

optimum lter when using ltered back pro-

jection or reconstruction is crucial (Pires Jorge

et al. 1998).

A lter in SPECT is a data processing algorithm

that enhances image inormation, without

signicantly altering the components o the

input data, creating arteacts or losing inor-

mation. It should produce results that lead to

Figure 1a circular orbit

Figure 1b elliptical orbit

Figure 1a Figure 1b

1a) is dened by a xed distance rom the axis

o rotation to the centre o the camera surace

or all angles. Elliptical orbits (Fig. 1b) ollow

the body outline more closely.


22/44

a correct diagnosis. Incorrect or over-ltering

may produce adverse eects by reducing ei-

ther resolution or contrast, or by increasing

noise.

A lter in SPECT, being a processing algorithm,

operates in the requency-amplitude domain,

which is obtained rom the spatial domain by

the Fourier transorm. In the spatial domain,the image data obtained can be expressed by

proles o any matrix row or column show-

ing the activity distribution (counts) as a unc-

tion o distance (pixel location). The Fourier

method assumes that this prole is the sum

o several sine and cosine unctions o dier-

ent amplitudes and requencies. The Fourier

transorm o the activity distribution o a given

prole is a unction in which the amplitude othe sine or cosine unctions is plotted against

the corresponding requency o each. This rep-

resentation is also called the image requency-

amplitude domain.

In input data, the highest requency that

can be measured is named the Nyquist re-

quency, which is determined by the matrix

size as well by the scintillation detector size

and is expressed by the ormula: fn=1/(2d)

where fn is the Nyquist requency and dis the

acquisition pixel size. For example, when using

a 6464 matrix with a 41-cm gamma camera

UFOV, the pixel size (d) is 0.64 cm. Thereore

the Nyquist requency is 0.78. This means that

any input data where the requency is higher

than 0.78 cannot be measured.

The input data plotted in the image requen-

cy-amplitude domain present three com-

ponents that are partially superposed: the

low-requency background, useul or target

data and the high-requency noise. Here back-

ground does not mean surrounding natural

radiation or surrounding non-tissue activity

but rather the low-requency waves gener-

ated by the reconstruction process, such asthe well-known star arteact that appears in

an unltered back projection. The high-re-

quency noise is related to background and

scatter radiation or statistical count fuctua-

tions during SPECT acquisition, which may

induce image distortions.

Usually SPECT ltered back projection couples

a ramp lter with an additional ltering (e.g.Hann, Hamming, Parzen). The ramp lter is

so called as its shape looks like a ramp and

it will eliminate an important portion o the

unwanted low-requency background. How-

ever, the ramp lter amplies the contribution

o the high-requency noise to the image. This

is why it is recommended that an additional

lter be coupled with the ramp lter in order

to smooth an image where some details could

appear very noisy. The degree o smoothing

or each additional lter is under the control

o the user, as s/he has to decide the cut-

o requency at which the lter will be ap-

plied. The cut-o requency is the requency

value that denes the maximum requency

acceptable (which may contain useul data)

while ignoring the higher requency noise.


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Obviously the maximum value o the cut-o

requency or a given additional lter is the

Nyquist requency.

As parathyroid adenomas appear as small hot

spots, requently within normal thyroid activ-

ity, the optimum choice o lter is a high-pass

type lter with a cut-o requency value close

to the Nyquist requency. A high-pass typelter will be applied in order to eliminate the

background image components (low requen-

cy) and conserve target data, although some

noise (high requency) will have to be toler-

ated because o the low image smoothing.


24/44

Patient preparationAudrey Taylor and Nish Fernando

Patient identication

To minimise the risk o a misadministration:

Establish the patients ull name and other

relevant details prior to administration o

any drug or radiopharmaceutical.

Corroborate the data with inormation pro-

vided on the diagnostic test reerral.

I the inormation on the reerral orm does

not match the inormation obtained by the

identication process, then the radiopharma-

ceutical/drug should not be administered to

the patient. This should be explained to the

patient and clarication sought as soon as

possible by contacting the reerral source.

The patient/parent/guardian/escort shouldbe asked or the ollowing inormation, which

should then be checked against the request

orm and ward wristband in the case o an

in-patient:

Full name (check any spellings as appropri-

ate, e.g. Steven vs Stephen)

Date o birth

Address

I there are any known allergies or previous

reactions to any drug, radiopharmaceutical,

iodine-based contrast media or products

such as micropore or Band-Aids

A minimum o TWO corroborative details

should be requested and conrmed as cor-

rect.

The ollowing inormation should be checked

with the patient/parent/guardian/escort

where appropriate:

Reerring clinician/GP/hospital

Any relevant clinical details

Conrmation that the patient has complied

with the dietary and drug restrictions

Conrmation that the results o correlative

imaging (e.g. echocardiography, angiogra-

phy, etc.) are available prior to the study, andnoting o any recent interventions

I in doubt, do not administer the radiophar-

maceutical or drug and seek clarication.

Specic patient groups

This is a guide only. Patients who are unable to

identiy themselves or any o a variety o rea-

sons should wear a wrist identication band.

Hearing diculties: Use written questions

and ask the patient to supply the inormation

verbally or to write their responses down.

Speech diculties: Ask the patient to write

down their name, date o birth and address

and other relevant details.


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Chapter 4: Patient preparation

Language diculties: I an accompanying

person is unable to interpret the questions,

then the study should be rebooked when

a member o sta or relative with the ap-

propriate language skills or an interpreter

is available.

Unconscious patient: Check the patients

ID wristband or the correct name and dateo birth. I no wristband is attached, ask the

nurse looking ater the patient to positively

conrm the patients ID.

Conused patient: I the patient is an in-pa-

tient, check the patients ID wristband or

the correct name and date o birth. I no

wristband is attached, ask the nurse looking

ater the patient to positively conrm thepatients ID. I the patient is an out-patient,

ask the person accompanying the patient

to positively conrm the patients ID.

I a relative, riend or interpreter provides in-

ormation re the patients name, date o birth

etc., it is advisable or them to sign so as to

provide written evidence conrming the rel-

evant details.

Patients can be required to send in a list o

medications, approximate height, weight and

asthma status so that stressing drugs can be

chosen in advance. They should be advised to

contact the department i they are diabetic so

as to ensure that the appropriate guidance is

given with regard to eating, medication etc.

A ull explanation o the procedure should be

given, including, risks, contraindications and

side-eects o stress agents used, time taken

or scan, the need to remain still etc.

I the patients are phoned prior to appoint-

ment, it acts as a reminder o the test and

gives the patient an opportunity to discuss

any concerns.


26/44

QUESTIONNAIRE FOR ALL FEMALE PATIENTS OF CHILD BEARING AGE

(12 55 YEARS)

We are legally obliged under The Ionising Radiation (Medical Exposure) Regulations 2000

to ask emales o child bearing age who are having a nuclear medicine procedure whether

there is any chance they may be pregnant or breasteeding.

Prior to your test, please answer the ollowing questions in order or us to comply with

these regulations:

PATIENT NAME ................................................................................................................................... D.O.B

1. Have you started your periods? (please tick appropriate box)

Y What is the date o your last period ...................................................................

N Please sign below and we can then proceed with your test

OR Have you nished your periods / had a hysterectomy (please tick appropriate box)

Y Please sign below and we can then proceed with your test

N What is the date o your last period

2. Is there any chance you may be pregnant (please tick appropriate box)

Y We will need to discuss your test with you beore we proceed

Not sure We will need to discuss your test with you beore we proceed


3. Are you breasteeding? (please tick appropriate box)

Y We will need to discuss your test with you beore we proceed


Pregnancy

Women o childbearing potential should have their pregnancy status checked using a orm

such as the example below:


27/44

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Chapter 4: Patient preparation

I have read and understood the questions above and conrm that I am not pregnant or

breasteeding and that I am aware that ionising radiation could damage a developing

baby.

Signed: ____________________________________ Date: _____________________

(Patient)

For all patients under 16 years o age

I have read and understood the question above and conrm that the patient named is not

pregnant or breasteeding

Signed: ____________________________________ Date: _____________________

Parent Guardian (please tick appropriate box)

THIS FORM WILL BE CHECKED / DISCUSSED PRIOR TO THE START OF THE TEST

The operator administering the radiopharma-

ceutical should advise the patient on minimis-

ing contact with pregnant persons and chil-

dren. In addition, the operator administering

the radiopharmaceutical should check that

any accompanying person is not pregnant

(e.g. escort nurse)

Parathyroid patient preparation

I possible, and under guidance rom the

reerring clinician, the patient should be o

any thyroid medication or 46 weeks prior

to imaging.

Establish whether the patient has had any

imaging procedure using iodine contrast


28/44

within the last 6 weeks (CT with contrast,

IVU etc). Allow a period o 6 weeks between

these procedures and thyroid imaging.

Iodine-containing medications may have to

be withdrawn, and the reerring clinicians

advice should be sought. These medica-

tions include: propylthiouracil, mepro-

bamate, phenylbutazone, sulphonamides,corticosteroids, ACTH, perchlorate, anti-

histamines, enterovioorm, iodides, Lugols

solution, vitamin preparations, iodine oint-

ments and amiodarone.

Beore any pharmaceuticals are ordered,

check whether the patient has had a total

thyroidectomy. I this is the case, then the

subtraction technique should not be car-ried out and consideration should be given

to undertaking a dual-phase 99mTc-sestamibi

study.

Ask the patient whether he or she has any

thyroid disorders such as thyrotoxicosis,

hypothyroidism, thyroid nodules or thy-

roid goitre. These conditions can increase

instances o alse-positive 99mTc-sestamibi

uptake and also aect 123I sodium iodide

uptake. In the case o hypothyroidism, do

not carry out the subtraction technique and

consider undertaking a dual-phase 99mTc-

sestamibi study.

Ask the patient whether he or she is able to

lie supine or the duration o the study and

also whether he or she is claustrophobic.

Consider another imaging modality i the

patient cannot lie still or the duration o the

study owing to discomort or anxiety.

Although 123I sodium iodide contains little

carrier-ree iodide, it is important to ask

the patient about any adverse reactions

to iodide in the orm o contrast media ormedication. I positive, seek the advice o

the lead clinician.


29/44

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Imaging protocolsNish Fernando and Sue Huggett

There are many variations in the imaging pro-

tocols used. For dual-isotope studies where

images are acquired sequentially with the sec-

ond nuclide being injected ater the rst set o

images, consideration must be given to timing

o uptake and downscatter rom the higher

energy nuclide when considering which

nuclide to use rst. O course, simultaneous

imaging, although aected by downscatter,obviates problems o image registration.

One subtraction and one washout technique

are described, including SPECT imaging, as ex-

amples only. Explanations have been given or

the choices so that adaptations can be made

with knowledge o their eects.

SPECT/CT has been suggested as a suitabletechnique to increase the sensitivity o de-

tection (Gayed et al. 2005) but is beyond the

scope o this booklet.

123I sodium iodide/99mTc-sestamibi

subtraction

Give a ull explanation o the procedure to the

patient. In particular, stress the importance

o keeping still during the acquisition.

Ensure good venous access. A venon with

a three-way tap system into a vein in the

patients arm or the back o the hand is

more convenient than a butterfy needle

as veins more requently collapse around a

buttery needle than around the plastic o a

venon. Also, the patient has more reedom

o movement i a venfon is inserted.

Inject 123I sodium iodide ollowed by a saline

ush o 10 ml. Wrapping a bandage around

the arm or hand where the venfon is sited

will protect it during the period o delay.

At 0 min post 123I injection, ask the pa-

tient to empty the bladder. Ask the pa-tient whether he or she understands the

procedure. Again, stress the importance

o keeping still.

At 50 min post 123I injection, position the pa-

tient supine on the gamma camera couch.

Ensure the neck is extended by positioning

his/her shoulders on a pillow. Use sand-

bags and a strap to immobilise the headand neck. Ensure the patient is comortable

and understands the need to keep still. A

pillow placed underneath the knees can

reduce back discomort.

Position the patient so that an anterior image

o the thyroid and mediastinum can be ob-

tained, allowing any ectopic tissue to be in-

cluded in the image. Place the patients arm

that has the venfon and three-way system

onto an arm rest. Ensure patency o the ven-

fon by fushing through with saline. Re-site

the venfon i the vein has collapsed.

Start acquisition at 60 min post 123I sodium

iodide injection using a dual-isotope dy-

namic acquisition with non-overlapping


30/44

0

windows or 99mTc (-10% to +5% about

the peak at 140 keV) and 123I (-5% to +10%

about the 159-keV peak).

Acquire 2-min rames or 20 min using a

zoom o .0 and a matrix o 128128. A

dynamic acquisition is preerable to a static

one as movement correction, provided it is

in the x- or y-direction, can be applied to theimages. The large zoom is chosen in order

to increase spatial resolution. However, this

will increase noise in the image and so the

acquisition must be o sucient duration

to compensate or this.

Pure iodide images may be acquired or 10

min. As well as being critical or processing,

these pure iodide images can be benecialin reducing alse-positive cases due to thy-

roid disease.

Without any patient movement, inject 99mTc-

sestamibi ollowed by a 10-ml saline fush,

between the 11th and 12th minute and

continue the acquisition or 30 min.

As a large zoom has been used, it is advis-

able at the end o the dynamic acquisition

to carry out an unzoomed image to include

the salivary glands and the heart. This will

ensure the detection o any ectopic para-

thyroid glands, which can occur in the re-

gion o the unzoomed image. Acquire this

image on the same dual-isotope settings or

300 s onto a matrix o 256256.

Processing

In order to detect the increased uptake o99mTc-sestamibi in the parathyroid tissue it is

necessary to subtract the 123I image rom the

99mTc-sestamibi image.

The precise computer protocol will vary rom

centre to centre and even rom camera system

to camera system. However, all protocols willollow the same basic steps.

Movement correction

As the images have been acquired simultane-

ously, there will be no need to match the posi-

tions by shiting either image, but the images

should be checked or movement and any

correction algorithms applied beore com-

mencing. This can be as simple as checkingall the rames and rejecting any with blurring

beore the rames are summed. This will not

help i the patient has moved to a dierent

position rather than having coughed or swal-

lowed deeply and returned to the original

position.

I overall movement has occurred, the situa-

tion may be rescued i the subsequent rames

can be shited by reerence to some standard

point (sometimes the hottest pixel) or even

by eye.

The subtraction

Both sets o rames (corrected i necessary)

are summed to make one 99mTc and one 123I

image.


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1

Chapter 5: Imaging protocols

There will be more counts in the thyroid on the123I image, so it must be matched to the 99mTc

image beore subtraction and a scaling actor is

used so that the counts in the subtraction im-

age are reduced by this actor, pixel by pixel.

The simplest technique reduces the image

to be subtracted to, or example, 30%, 0%,

50%, 60% and 70% o its original values, andthese images are subtracted in turn rom the99mTc-sestamibi image, that which gives the

best result or eliminating the thyroid tissue

being chosen by eye.

A more automated system will draw a region

o interest around the normal thyroid on the123I image by allowing the operator to choose

the count contour line which best represents itsedges. The counts in this region are then com-

pared against the counts in the same region on

the 99mTc image. The scaling actor is calculated

rom the ratio o these two values. This adjusted

image is then subtracted rom the 99mTc image

and the results displayed as a new image. Again,

there are usually two or three options oered or

the operator to choose the best result.

SPECT imaging

Additional SPECT imaging gives increased

sensitivity and more precise anatomical lo-

calisation. Acquiring both early and delayed

SPECT can be a useul addition to either the

dual-phase 99mTc-sestamibi method or the

dual-isotope 123I/99mTc-sestamibi subtraction

method.

Early SPECT should be acquired 1030 min

ater the 99mTc-sestamibi injection and de-

layed SPECT at around 3 h post injection.

The camera is peaked or both 99mTc and123I as beore.

An 180o acquisition optimises the time close

to the area o interest and attenuation isnot a problem with structures so close to

the body surace.

Acquisition should start with the camera

head at 270o; proceed in a clockwise rota-

tion and stop at 90o.

I the acquisition is carried out on a double-

headed camera, a 90o L-Mode SPECT will beuseul and more counts will be collected as

both heads are used or the acquisition.

Contouring can be used i available, al-

though the patient should be warned i

the camera will move closer during the

acquisition.

It should be ensured that the zoom chosen

allows adequate coverage o the mediasti-

num to locate any ectopic glands there.

Using a zoom o 2 will ensure better spatial

resolution than no zoom, and there should

be enough coverage o the mediastinum.

A 6464 matrix is sucient or the expected


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resolution and will optimise counts per pixel

and hence reduce noise.

30 60-s rames is manageable or the patient

and will maximise counts in the image.

For delayed SPECT, increasing the time

per projection to 90 s will restore the total

counts.

Processing

The data may be reconstructed using the

methods o ltered back projection or itera-

tive reconstruction. Streak arteacts may be

seen in data reconstructed by ltered back

projection and these will not occur or the

iterative method.

The raw data can be viewed as a rotating

image and the limits or the region to be

reconstructed chosen.

The region should extend rom the parotid

glands to the mediastinum to locate any

ectopic tissue.

The reconstruction programme with cho-

sen lters is initiated.

Once the reconstruction is completed, the

images are viewed in the transverse, coronal

and sagittal planes.

Datasets can be viewed as volumetric dis-

plays as well as tomographic slices.

99mTc-sestamibi washout technique

I 99mTc-sestamibi is used alone, the two sets

o images (early and delayed) are inspected

visually.

740 MBq 99mTc-sestamibi is injected using the

same protocols or patient preparation, i.e.

ID and LMP checks/explanation to patient as

beore and imaging typically at 10 min and23 h

The camera is peaked or technetium and

a low-energy high-resolution collimator

can be used as images can be taken or

a sucient time to avoid statistical noise

problems and pinhole collimators are used

in some centres. Zoom can be used but

remember the possibility o ectopic tissue.

Neck and mediastinum views are taken with

patient positioning as beore. Again, a single

view o 600 s counts can be taken or a series

o 1060-s rames acquired so that move-

ment arteacts can be corrected.

The same parameters and positioning must

be used or the 10-min and late views

Right and let anterior oblique views can be

obtained i required.

SPECT can be used in this case also.

All lms should be correctly annotated with L,

R and anatomical markers and labelled.


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Technical aspects o probe-guided surgery orparathyroid adenomasDomenico Rubello

Bilateral neck exploration (BNE) still represents

the gold standard approach in patients with

primary hyperparathyroidism (pHPT). Howev-

er, surgical approaches to pHPT patients have

altered signicantly in many surgical centres

during the past decade, with the development

o minimally invasive parathyroidectomy using

endoscopic surgery or radio-guided surgery

(MIRS). This development can be attributed totwo main reasons: (a) the consciousness that

pHPT is due to a single parathyroid adenoma

in the majority o patients (at least 85%), and

(b) the technical improvements introduced

into surgical practice with the availability o

microsurgery instruments, endoscopes, intra-

operative measurements o quick parathyroid

hormone (QPTH) and gamma probes.

New approaches to minimally invasive para-

thyroidectomy consisting in the removal o a

solitary parathyroid adenoma via a small 12

cm skin incision have been widely adopted. O

course, in contrast to BNE, minimally invasive

parathyroidectomy always requires accurate

preoperative imaging in order (a) to establish

whether the parathyroid adenoma is eec-

tively solitary and (b) to locate precisely the

enlarged gland. The present chapter ocusses

mainly on technical aspects o the MIRS tech-

nique. Moreover, the MIRS technique devel-

oped in our centre is based on the injection

o a very low 99mTc-sestamibi dose 37 MBq

compared with the traditional MIRS tech-

nique, which uses a high 99mTc-sestamibi

dose 740925 MBq.

Selection criteria or ofering MIRS

When planning MIRS (unlike when perorm-

ing BNE), strict inclusion criteria need to be

ollowed: (a) evidence at 99mTc-sestamibi scin-

tigraphy o a solitary parathyroid adenoma;

(b) intense 99mTc-sestamibi uptake in the para-

thyroid adenoma; (c) absence o concomitant

thyroid nodules at 99mTc-sestamibi scintigraphy

and high-resolution (10 MHz) neck ultrasound;(d) no history o amilial HPT or multiple endo-

crine neoplasia; and (e) no history o irradia-

tion to the neck. O note, previous thyroid or

parathyroid surgery is not a contraindication

to MIRS. When these inclusion criteria are

adopted, approximately 6070% o pHPT pa-

tients can be oered MIRS. The main reason or

exclusion is the presence o 99mTc-sestamibi-

avid thyroid nodules, which, by mimicking aparathyroid adenoma, can cause alse posi-

tive results during surgery. Figure 1 shows a

patient scheduled or MIRS while Fig. 2 shows

a patient excluded rom MIRS.

Preoperative imaging protocol

In our protocol, preoperative imaging proce-

dures include single-session 99mTc-sestamibi

scintigraphy and neck ultrasound (Norman

and Chheda 1997; Costello and Norman

1999; Mariani et al. 2003; Rubello et al. 2000).

In patients with concordant 99mTc-sestamibi

and ultrasound results (both positive or nega-

tive), no urther imaging is perormed, while

in cases with discrepant ndings (99mTc-sesta-

mibi positive and US negative) a tomographic

(SPECT) examination is obtained to investi-


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gate a possible ectopic or deep position o the

parathyroid adenoma. SPECT is obtained just

ater the completion o planar 99mTc-sestamibi

scintigraphy, thus using the same radiotracer

dose; in this way, 99mTc-sestamibi re-injection is

not necessary, thus avoiding additional radia-

tion exposure to the patient and personnel.

In other centres, preoperative 99mTc-sestamibi

scintigraphy alone is considered a sucienttool or the planning o MIRS.

Intra-operative MIRS protocol

Table 1 shows the steps in the MIRS protocol

used in our centre.

A collimated gamma probe is recommended

with an external diameter o 111 mm. A

non-collimated probe, which can be used orsentinel lymph node biopsy, is not ideal or

parathyroid surgery owing to the relative com-

ponent o diuse and scatter radioactivity de-

riving rom the anatomical structures located

near to the parathyroid glands, mainly related

to the thyroid gland. Probes utilising either a

NaI scintillation detector or a semiconductor

detector have proved adequate or MIRS.

A learning curve o at least 2030 MIRS op-

erations is recommended or an endocrine

surgeon. During these, the presence in the

operating theatre o a nuclear medicine phy-

sician is usually considered mandatory. In

the opinion o the writer, the presence o a

nuclear medicine technician, with expertise

in probe utilisation, is very useul in helping

the surgeon to become more skilled in the

use o the probe.

The probe is usually handled by the surgeon,

who should measure radioactivity in dier-

ent regions o the thyroid bed and neck in an

attempt to localise the site with the highest

count rate beore commencing the operation.

This site is likely to correspond to the parathy-roid adenoma. Then, during the operation, the

surgeon should measure the relative activity

levels in the parathyroid adenoma, thyroid

bed and background. Moreover, a check o

the empty parathyroid bed ater removal

o the parathyroid adenoma is a very useul

parameter to veriy the completeness o re-

moval o hyperunctioning parathyroid tissue.

Ex vivo measurement o any removed surgicalspecimen should be done to veriy the total

clearance o the parathyroid adenoma. The

calculation o tissue ratios parathyroid to

background (P/B) ratio, thyroid to background

(T/B) ratio, parathyroid to thyroid (P/T) ratio

and the empty parathyroid bed to background

(empty-P/B) ratio can be useul in evaluating

the ecacy o MIRS. The tissue ratios obtained

in a large series o 355 pHPT patients operated

on in our centre are reported in Table 2.

Attention has to be given to avoidance o

intra-operative alse negative results due to99mTc-sestamibi-avid thyroid nodules and to

stagnation o the radiotracer within vascular

structures o the neck and thoracic inlet: in this

regard, the careul acquisition and evaluation


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Table 1. Steps in minimally invasive radioguided surgery (MIRS) o parathyroid adenomas using

the low 99mTc-sestamibi dose protocol developed in our centre

Blood samples are drawn rom a peripheral vein both beore commencing surgery and 10 min

ollowing the removal o the parathyroid adenoma to measure intra-operative QPTH levels

37 MBq o99mTc-sestamibi is injected in the operating theatre 10 min beore the start o

surgery

Prior to surgical incision, the patients neck is scanned with an 11-mm collimated probe to

localise the site with the highest count rate, corresponding to the cutaneous projection o

the parathyroid adenoma

A transverse midline neck access (approximately 1 cm above the sternal notch) is preerred

because conversion to BNE is easily obtained i necessary

An 11-mm collimated probe is repeatedly inserted through a 2-cm skin incision, guiding the

surgeon to the maximum count rate area corresponding to the parathyroid adenoma

In some patients with a parathyroid adenoma located deep in the neck, ligature o the middle

thyroid vein and o the inerior thyroid artery is required

Radioactivity o the parathyroid adenoma, thyroid gland and background is measured with

the probe

Radioactivity is measured ex vivo to conrm successul removal o parathyroid tissue

Radioactivity o the empty operation site is checked to evaluate the completeness o para-

thyroid tissue removalTissue ratios are calculated (P/B, P/T etc.)

QPTH, quick parathyroid hormone; BNE, bilateral neck exploration; P/B, parathyroid to back-

ground ratio; P/T, parathyroid to thyroid ratio


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Chapter 6: Technical aspects of probe-guided surgery for parathyroid adenomas

tamibi dose protocol, with a success rate in

the intra-operative detection o parathyroid

adenoma o approximately 9698%, without

major intra-operative surgical complications. It

is likely that Normans single-day protocol will

be preerable in patients with a low likelihood

o nodular goitre whilst our dierent-day pro-

tocol appears preerable in areas with a higher

prevalence o nodular goitre.

Irrespective o the type o MIRS protocol used,

the principal advantages o MIRS over tradi-

tional BNE can be summarised as: (a) a small

skin incision with avourable cosmetic results,

(b) a shorter operating time, (c) the possibility

o perorming MIRS under local anaesthesia,

(d) a shorter hospital recovery time, (e) the

possibility o same-day hospital discharge, ()

lower post-surgical time and (g) lower costs.

Table 2. Probe tissue ratios calculated during MIRS or parathyroid adenoma removal (n=355

pHPT patients)

P/B ratio = 1.64.8 (mean 2.60.5)

P/T ratio = 1.12.8 (mean 1.50.4)

T/B ratio = 1.51.8 (mean 1.60.1)

Empty-P bed/B ratio = 0.91.1 (mean 1.00.03)

TN/P ratio = 0.51.5 (mean 1.00.4)

P=parathyroid

T=thyroid

B=background

TN=thyroid nodule


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Table 3. Radiation dose to operating theatre personnel during MIRS with the low (37 MBq)99mTc-sestamibi dose protocol used in our centre

Gy/hour Gy/year*

Surgeons body 1.2 120

Surgeons hands 5.0 500

Anaesthesiologist 0.7 70

Instrument nurse 1.1 110

Other nurses 0.1 10

*Estimated or 100 interventions, each lasting 60 min

Figure 1. Preoperative dual-tracer parathyroid subtraction scintigraphy. Left image: 99mTc-pertech-

netate scan showing a normal thyroid gland. Middle image: 99mTc-sestamibi scan showing an

area o radiotracer uptake juxtaposed to the lower pole o the let thyroid lobe. Right image:

Subtraction (99mTc-sestamibi-99mTc-pertechnetate) image, clearly showing a let inerior para-

thyroid adenoma. This patient was oered MIRS.


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Chapter 6: Technical aspects of probe-guided surgery for parathyroid adenomas

Figure 2. Preoperative dual-tracer parathyroid subtraction scintigraphy. Left image: 99mTc-pertech-

netate scan showing a multinodular goitre with some hyperunctioning nodules (three in the

right thyroid lobe, one in the let thyroid lobe). Middle image: 99mTc-sestamibi scan showing

a picture similar to the 99mTc-pertechnetate image plus a let superior area o exclusive 99mTc-

sestamibi uptake. Right image: subtraction (99mTc-sestamibi-99mTc-pertechnetate) image clearly

showing a let superior parathyroid adenoma. This patient was excluded rom MIRS due to the

coexistence o a solitary parathyroid adenoma and multinodular goitre with multiple99m

Tc-sestamibi-avid thyroid nodules in both thyroid lobes


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0

Chapter 1

Reerences1. Akerstrm G, Malmaeus J, Bergstrm R. Surgical anato-

my o human parathyroid glands. Surgery 1984;95:1421.

2. Al Zahrani AA, Levine MA. Primary hyperparathyroidism.

Lancet 1997; 349:12331238.

3. Bilezikian JP, Potts JT Jr, Fuleihan Gel-H, Kleerekoper M,

Neer R, Peacock M, et al. Summary statement rom a work-

shop on asymptomatic primary hyperparathyroidism: a

perspective or the 21st century [review]. J Clin EndocrinolMetab 2002;87:53535361.

4. Borley NR, Collins REC, ODoherty M, Coakley A. Tech-

netium 99m-sestamibi parathyroid localization is accurate

enough or scan-directed unilateral neck exploration. Br J

Surg 1996;83:989991.

5. Coakley AJ, Kettle AG, Wells CP, ODoherty MJ, Collins

REC. 99mTc sestamibi - a new agent or parathyroid ima-

ging. Nucl Med Commun 1989;10:791794.

6. Giordano A, Rubello D, Casara D. New trends in parathyroid

scintigraphy [review]. Eur J Nucl Med 2001;28:14091420.

7. Haber RS, Kim CK, Inabnet WB. Ultrasonography

or preoperative localization o enlarged parathyroid

glands in primary hyperparathyroidism: comparison with

(99m)technetium sestamibi scintigraphy. Clin Endocrinol

(Ox ) 2002;57:241249.

8. Heath H, Hodgson SF, Kennedy MA. Primary hyperpara-

thyroidism. Incidence, morbidity, and potential economic

impact in a community. N Engl J Med 1980;302:189193.

9. Hindi E, Melliere D, Perlemuter L, Jeanguillaume C,

Galle P. Primary hyperparathyroidism: Higher success rate

o rst surgery ater preoperative Tc-99m-sestamibi/I-123

subtraction scanning. Radiology 1997;204:221-228.

10. Hindi E, Mellire D, Jeanguillaume C, Perlemuter L,

Galle P. Parathyroid imaging using simultaneous double-

window recording o Tc-99m-sestamibi and 123I. J Nucl

Med 1998;39:11001105.

11. Hindi E, Urea P, Jeanguillaume C, Melliere D, Berthelot

JM, Menoyo-Calonge V, et al.. Preoperative imaging o pa-

rathyroid glands with technetium-99m-labelled sestamibi

and iodine-123 subtraction scanning in secondary hyper-parathyroidism. Lancet 1999;353:22002204.

12. Hindi E, Melliere D, Jeanguillaume C, Urena P, deLabri-olle-Vaylet C, Perlemuter L. Unilateral surgery or primary

hyperparathyroidism on the basis o technetium Tc 99m

sestamibi and iodine 123 subtraction scanning. Arch Surg

2000;135:14611468.

13. Lee JA, Inabnet WB 3rd. The surgeons armamentarium

to the surgical treatment o primary hyperparathyroidism

[review]. J Surg Oncol 2005;89:130135.

14. Levin KE, Clark OH. The reasons or ailure in parathyroid

operations. Arch Surg 1989;124:911915.

15. Liu RC, Hill ME, Ryan JA Jr. One-gland exploration or me-

diastinal parathyroid adenomas: cervical and thoracoscopic

approaches. Am J Surg 2005;189:601605.

16. Lundgren E, Rastad J, Thurfell E, Akerstrm G, Ljunghall

S. Population-based screening or primary hyperparathyro-

idism with serum calcium and parathyroid hormone values

in menopausal women. Surgery 1997; 121:287294.

17. Martin D, Rosen IB, Ichise M. Evaluation o single isoto-

pe technetium-99m-sestamibi in localization eciency or

hyperparathyroidism. Am J Surg 1996;172:633636.

18. Marx SJ, Simonds WF, Agarwal SK, Burns AL, Weinstein

LS, Cochran C, et al. Hyperparathyroidism in hereditary

syndromes: special expressions and special managements

[review]. J Bone Miner Res 2002;17 Suppl 2:N37N43.

19. Molinari AS, Irvin GL 3rd, Deriso GT, Bott L. Incidence

o multiglandular disease in primary hyperparathyroidism

determined by parathyroid hormone secretion. Surgery

1996;120:934937.

20. Mullan BP. Nuclear medicine imaging o the parathyroid

[review]. Otolaryngol Clin North Am 2004;37:909939, xixii.

21. Peri S, Fessi H, Tassart M, Younsi N, Poli

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