SUS-Malmö

Challenges in nuclear medicine

radiation dosimetry

Sören Mattsson

Medical Radiation Physics, Lund University and

Skåne University Hospital Malmö, Sweden

ICRP Committe 3

Nuclear medicine is expanding• Growing use of PET/CT and SPECT/CT (now also

PET/MRI)

• Oncology and also neurological and cardiac diagnostic

procedures

• Increasing use of radiotracers in surgical practices

• New radiopharmaceuticals (increasing importance

of shortlived radionuclides)

Nuclear medicine stands for a small number of

investigations compared to diagnostic radiologyExamples:

Globally (1997-2007): 1% of diagn radiological exams

Sweden (2005): 2%

USA (2006): 5% of investigations 26% of collective dose

_

_

_

_

_

1

10

100

0.1

0.01

PET/CT FDG, SPECT/CT, CT trauma (foetus)

CT colon

CT thorax/lungs SPECTCT head Low dose CT colonCT facial skeletonLow dose CT lungs

Low dose CT facial skeleton

99mTc-substances

Colon

Coronary angiography

UrographyLumbar spine

Mammography Lungs

Facial skeletonHand, foot

Teeth (single picture)

Effective dose, mSv

CT abdomen/pelvis, PET-FDG

PET/CT and SPECT/CT are

high-dose investigations

Nuclear medicine also for therapy

Small (Sweden 2010: 2.8%) in relation to nuclear medicine

diagnostic procedures

Therapeutic nuclear medicine

• Hyperthyroidism and thyroid cancer 131I-iodide

• Polycytemia 32P-orthophosphate

• Severe pain in metastatic bone disease 89Sr-chloride153Sm- or 177Lu-EDTMP186Re-EHDP223Ra-chloride

• Tumours (monoclonal antibodies and 90Y-Zevalin

peptides, receptor specific substances) 90Y-,131I-, 177Lu-, 211At-MaB

• Neuroendocrine tumours 131I-mIBG90Y-, 177Lu-octreotate

• Liver tumours 90Y-microspheres (SIRT)

Patients

TherapyNTCP/TCP for the INDIVIDUAL patient

stochastic risks; can not be assessed for an individual

patient, but for a population of patients

DiagnosticsStaff

Dosimetry in nuclear medicine

We want to know the absorbed dose in all irradiated tissues/organs

of interest

• Biokinetics

• Dose calculations (radionuclide decay, body geometry, organ volume, etc…)

Varying needs for accuracy in therapy and diagnostics

Therapy: better than +/- 5% (like external radiation therapy)

Diagnostics: +/- say 20%

Can we meet these needs for accuracy?

The major contributor to uncertainty in absorbed dose estimations

is the activity quantification and how frequently the

measurements can be done

Activity, A(t)

Time, t+

+

++

++

+

Biokinetics, A(t)• Quantification of activity in organs and tissues

• Blood and excreta

sampling

Methods:

1) Serial planar gamma camera imaging, conjugate view method

(geometric mean to anterior-posterior projections), attenuation and

scatter correction

2) SPECT(/CT) with attenuation and scatter corrections

3) PET(/CT) attenuation and scatter correction

Most

quantification

methods based

on iterative

methods

10 min 1 h 4 h 24 h 48 h

Sydoff et al., 2012

A patient measured at 5 times after injection of 123I-ioflupan

Sydoff et al., 2012

Ten 123I-ioflupan patients 10 minutes after injection

Booij et al., 1998

Mean activity in blood

Cumulated urinary excretion

(decay corrected)

BiokineticsAim: Detailed compartment models

Reality: Descriptive biokinetic models

• The biokinetics is often described as a sum of exponentials

• These are “net models” which describes what we can measure

• There is usually no unique transformation of a net model to a

compartment model. (This is possible only if the structure of the

compartment model is known).

111In octreotide

4 hours after inj. 24 hours after inj.

front frontback back

Activity A(rs,t)

Cumulated activity= ∫A(rs,t)dt = A(rs)~

Time

S - Source organ or tissue

Fs - Fractional distribution to S

T - Biological half-time for an uptake or

elimination component

a - Fraction of Fs taken up or eliminated with the

corresponding half-time. A negative value

indicates an uptake phase.

Ãs/Ao- Cumulated activity in S per unit of adm activity

Biokinetic data – Indium-labelled octreotide

From cumulated activities to organ/tissue absorbed dose

Computational models = ”Phantoms”

Diagnostics: ICRP Reference phantoms

Why?

To be able to compare information between hospitals

To be able to compare different investigation methods

Therapy:

Realistic phantoms tailored to the individual patient

Why?

Weight and lenght differ

Organ masses differ

Distances between organs differ

MIRD/ORNL Cristy and Eckermann Hermaphrodites

www.peddose.net

http://www.

virtualphantoms.

org/index.html

or tomo-

graphic

model

polygon

mesh

NURBS-

surfaces

Dose calculations

Protocols

Type of equipment/measurements

Image quantification (corrections performed; attenuation, scatter,

dead time, reconstruction parameters for SPECT or PET, background

subtraction)

Time points on time-activity curves. Integration

Bladder voiding interval

Dose computation model

For the effective dose calculation; Set of tissue-weighting factors

Number of participant in the study

1998

(printed late 1999)

ICRP Publication 80

(Addendum 2)10 new radiopharmaceuticals

+ recalculations of 19 frequently

used ones in Publ 53.

ICRP Publication 106

(A third amendment)33 radiopharmaceuticals in current

use. Recommendations on breast

feeding interruptions.

2008Task Group:

S. Mattsson

L. Johansson

B. Nosslin

T. Smith

D. Taylor

E/A0, µSv/MBq

99mTc-substances

0.001 0.01 0.1

99mTc-colloids (small), intratum. inj.

99mTc-pertechnetate, with blocking

99mTc-apticide

99mTc-DTPA

99mTc-phosphates and phosphonates

99mTc-EC

99mTc-MAG3

99mTc-RBC

99mTc-tetrofosmin (rest/exercise)

99mTc-ECD

99mTc-MIBI (rest/exercise)

99mTc-DMSA

99mTc-HM-PAO

99mTc-colloids (large)

99mTc-furifosmin

99mTc-MAB

99mTc-MAA

99mTc-WBC

99mTc-pertechnegas

99mTc-pertech, without blocking

99mTc-IDA derivatives

99mTc-markers, non-absorb per os

99mTc≈ 0.008 µSv/MBq

0.001 0.01 0.1

15O-water

82Rb-chloride

11C-thymidine

11C-acetate

11C-brain rec subst (generic mod)

11C-choline

11C-amino acids (generic mod)

11C-methionine

11C (realistic max mod)

18F-FLT

18F-FET

18F-choline

18F-FDG

18F-amino acids (generic mod)

18F-fluoride

18F-L-dopa

18F-brain rec subst (generic mod)

PET-substances

18F≈ 0.02 µSv/MBq

11C≈ 0.005 µSv/MBq

E/A0, µSv/MBq

E/A0, µSv/MBq

201Tl- 131,125,123I-, 111In-, 75Se-, 67Ga-, 51Cr-, 14C-, 3H-substances

0.001 0.01 0.1 1 10 100

51Cr-EDTA123I-MIBG

123I-fatty acids123I-iodide, after ablation, 1%

123I-MAA14C-urea (normal)

123I-brain rec subst (generic mod)131I-iodo hippurate

111In-octreotide67Ga-citrate

201Tl-chloride111In-MAA

3H-fat 123I-iodide, 35% thyroid uptake

131I-MAA131I-iodide, after ablation, 1%

75Se-HCAT14C-fat

131I-iodide, 35% thyroid uptake

11C 18F99mTc

0.001 0.01 0.1 1 10 100

14C-urea (normal)51Cr-EDTA

131I-iodo hippurate75Se-HCAT (low bg)

14C-urea (Helicobacter pos.)3H-fat

99mTc-colloids (small), intratum. inj.14C-fat

75Se-HCAT99mTc-pertechnegas

15O -water 99mTc-markers, non-absorbable (fluids) per os99mTc-markers, non-absorbable (solids) per os

99mTc-DMSA99mTc-MAG3

11C-thymidine 99mTc-DTPA

11C-amino acids (generic model) 11C-brain receptor substances (generic model)

99mTc-MAA11C-choline

99mTc-pertechnetate, with blocking99mTc-WBC

123I-iodide, 35% thyroid uptake 123I-fatty acids (BMIPP/IPPA)

99mTc-MIBI (rest)11C-methionine

99mTc-IDA derivatives11C-acetate

99mTc-colloids (large)82Rb-chloride

99mTc-phosphates and phosphonates99mTc-apticide

99mTc-EC99mTc-ECD

123I-MAB11C (realistic maximum model)

99mTc-tetrofosmin131I-iodide, 35% thyroid uptake

99mTc-MIBI 123I-MIBG

99mTc-furifosmin (exercise)99mTc-RBC

99mTc-pertechnetate, without blocking99mTc-furifosmin (rest)

123I-iodide, after ablation, 1% thyroid uptake18F-FDG 18F-FLT 18F-FET

99mTc-HM-PAO18F-choline99mTc-MAB

123I-brain receptor substances (generic model)18F-amino acids (generic model)

111In-octreotide18F-fluoride18F-L-dopa

18F-brain receptor substances (generic model)201Tl-chloride

67Ga-citrate 131I-iodide, after ablation, 1% thyroid uptake

111In-MAB131-MAB

131I111In67Ga201Tl

18F123I99mTc11C

99mTc14C3H

Effective dose per investigation, mSv

Can we meet the accuracy requirements?

Therapy: No and Yes?

Diagnostics: Yes and No

Serial planar imaging scans + SPECT in combination +/- 10-20%

PET +/- 10% if very accurate attenuation, scatter and random

corrections

“…the accuracy of quantifying the concentration of a radionuclide

in regions within the body can be < 5% with SPECT or PET

imaging, and provided there are no overlapping structures

containing radioactivity, similar accuracy can also be obtained

with planar gamma camera imaging” (Frey et al., 2012)

Challenges (Diagnostics):

•For some substances biokinetic data are old (more than 20

years). Need to generate new data on biokinetics and

dosimetry using state-of-the-art equipment

•Few subjects per study. More volunteers are needed.

•Biokinetic data for children

•Biokinetic data for various ages

•Gender specific data

•Biokinetic data for ill

•More uniform dosimetry protocols

•Dose distributions within organs and tissues

•Review of CT protocols for SPECT/CT and PET/CT imaging.

DRLs

•Epidemiological studies

Challenges (Therapy):

•Dose planning before therapy, No therapy without dose

planning!

•Individual patient biokinetics

•Individual dose calculations

•Dose distributions within organs and tissues

•Same protocol for different hospitals and clinics for

measurements of biokinetic data and for dosimetry

•A formalism for the addition of doses from nuclear

medicine therapy and external radiation therapy for

patients receiving both treatments (BED)

Thank you for listening! … and don´t forget to collect biokinetic data

from your patients!

Task Group on Radiation Dose to Patients from Radiopharmaceuticals

soren.mattsson@med.lu.se