Radionuclide imaging

SUDARSAN [email protected]

PINNAMANENI MEDICAL COLLEGE, VIJAYAWADA

Radionuclide Imaging & Its Applications

mailto:[email protected]

Electromagnetic Spectrum

Ionising radiation

• Alpha radiation – 2N+2P• Beta radiation – electron emitted by

a nucleus• Positron -similar to electron except

that it has a positive charge. PARTICULATE

• X-Rays• Gamma rays EM RADIATION

Types of Ionizing Radiation

Alpha ParticlesStopped by a sheet of paper

Beta ParticlesStopped by a layer of clothingor less than an inch of a substance (e.g. plastic)

Gamma RaysStopped by inches to feet of concreteor less than an inch of lead

RadiationSource

Gamma rays are not charged particles like a and b particles.

Gamma rays are electromagnetic radiation with high frequency.

When atoms decay by emitting a or b particles to form a new atom, the nuclei of the new atom formed may still have too much energy to be completely stable.

This excess energy is emitted as gamma rays

Accurate Diagnosis is key to Surgical practice

Accurate Diagnosis is key to Surgical practice

• X rays , CT

• Ultra Sound, MRI

• SPECT , PET

MRI SPECTfMRI

X-Ray

CTUltrasound

Diagnostic Procedure

Typical effective

dose (mSv)

Equivalent no. of chest radiographs

Approximately equivalent period of natural background

radiation

Chest X ray 0.02 1 3 days

Thyroid(Tc 99m)

1 50 6 months

Bone (Tc 99 m)

4 200 1.8 years

PET 5 250 2.3 years

CT abdomen 10 500 4.5 years

Hybrid Imaging

Hybrid Imaging

• PET-CT: radionuclide imaging devices are combined with CT in a single imaging system

• The resulting images display the functional data obtained from the radionuclide distribution (usually in color) overlaid on the anatomical information from CT (usually in grey scale)

Radiotherapy xNuclear Medicine

Nuclear medicine

• Nuclear medicine is a subspecialty within the field of radiology that uses very small amounts of radioactive material to diagnose or treat disease

• We need a short-lived radio nuclide which has to be combined to a pharmaceutical of interest and injected iv and this radio pharmaceutical goes and attaches to the organ of interest and we can catch the gamma rays emitted by it with help of gamma cameras and pictures are reconstructed in computer

• (in amounts of Pico molar concentrations thus not having any effect on the process being studied)

1. RADIONUCLIDE

2. PHARMACEUTICAL

3. GAMMA CAMERA

SPECT

1. RADIONUCLIDE

2. PHARMACEUTICAL

3. GAMMA CAMERA

Ideal Radionuclide

• Emits gamma radiation at suitable energy for detection with a gamma camera (60 - 400 kev, ideal 150 kev)

• Should not emit alpha or beta radiation

• Half life similar to length of test• Cheap• Readily available

Technetium

• This is the most common radio nuclide used in Nuclear Medicine.

• Taking its name from the Greek work technetos meaning artificial , it was the first element to be produced artificially.

99mTc

Excited Nucleus

Gamma ray

99Tc

Stable Nucleus

Photon Decay

1. RADIONUCLIDE

2. PHARMACEUTICAL

3. GAMMA CAMERA

Ideal radiopharmaceutical

• Cheap and readily available• Radionuclide easily incorporated

without altering biological behavior• Radiopharmaceutical easy to prepare• Localizes only in organ of interest• t1/2 of elimination from body similar to

duration of test

• Thyroid scintigraphy• Salivary gland study• Meckel’s diverticulum

scintigraphy

99mTc pertechnetate

• Interictal PET• Cerebral metabolism PET• Tumor imaging

18 FDG

• Parathyroid scintigraphy99mTc MIBI

• Bone scintigraphy

99mTc polyphos

phate

• Cardiac ventriculography• GI bleed study

99mTc red blood cells

• V/Q scan99mTc

albumin

99mTc sulphur colloid

• Esophageal transit and reflux

• GI bleed study

99mTc leucocytes

• White cell scintigraphy

99mTc iminodiacetic

acid derivatives

• Hepatobiliary study

• Diuresis renography • Renal tract obstruction

99mTc DTPA

• Static renal scintigraphy• Renal scarring

99mTc DMSA

• Somatostatin receptor study

111In pentetreo

tide

1. RADIONUCLIDE

2. PHARMACEUTICAL

3. GAMMA CAMERA

Gamma Camera

A gamma camera consists of three main parts:

Electronic systems

Detector

Collimator

Gamma Camera

Positron Emission Tomography

• PET is a nuclear medicine imaging technique that provides high-resolution tomographic images of the bio-distribution of a radiopharmaceutical in vivo .

• A PET scan measures important body functions, such as blood flow, oxygen use & glucose metabolism

• Radiopharmaceutical consists of positron-emitters, usually very short-lived and produced in cyclotrons.

• 18 F being one of the most optimal positron emitters for imaging

Glucose

FDG

Plasma Cell

Transport Phosphorylation Glycolysis

Glucose

18F-FDG 18F-FDG-6-P

Glucose-6-PGlycolysis

Glucose

18F-FDG

FDG

• Half-life (T 1/2 ) is 110 minutes

• Low average positron energy of 0.63 MeV

• Average positron range in tissue of 0.3 mm

• Delay a PET scan by 2 -3 weeks after surgical intervention

• 2 -3 weeks interval after chemotherapy.• 3 months after radiation therapy,• 6 to 8 weeks post-radiation therapy-

surgery.• Should not be performed on pregnant and

breast feeding patients.

• Malignant cells show an increased rate of glucose metabolism ,probably due to presence on cell surfaces of an abnormally large number of glucose transporters, along with increased hexokinase-mediated glycolysis and a reduced level of dephosphorylating by glucose -6-phosphate.

Uses • Detect primary , secondary cancer and

metastasis • Assess the effectiveness Cancer chemo therapy • Cancer recurrence • Mapping of brain and heart function • Evaluate brain abnormalities, such as tumors,

memory disorders and seizures and other central nervous system disorders

• Determine blood flow to the heart muscle and thus determine the effects of a heart attack, or myocardial infarction

Arrow points to "dead" myocardial tissue.

PET scan of a heart

Cardiac Imaging

Cerebral Imaging

• 99mTc-HMPAO : cross to BBB and fix in the brain proportionally to perfusion

• 18FDG : glucose metabolism• 99mTc-TRODAT : dopamine transporter• 111In-DTPA, 99mTc-DTPA : CSF dynamics, V-P

shunt patency study

PET image showing malignant breast mass (not revealed by CT, MRI or Mammo)

PET image of same patient with enlarged left axillary lymph nodes

The role of PET after chemotherapy

• Many neoplasms have an enhanced glucose metabolism compared to normal tissue.

• FDG provides functional data on tumor metabolism, complementary to morphologic imaging studies.

• Standard tool for decision making in lymphoma, Hodgkin`s disease, different solid tumors post chemotherapy.

• Germ cell tumors (GCT) are characterized by a high FDG uptake.

• Advantages• Disadvantages• Safety and Risk

Advantages

• Assesses body function and in monitoring flow rate

• Can measure body composition using dilution analysis.

• Whole body scanning • Response to radiotherapy and

chemotherapy

Disadvantages

• Generally poor resolution compared with other imaging modalities

• Radiation risks due to administered radionuclide

• Can be invasive, usually requiring an injection into the blood stream.

• Disposal of radio activity waste. • Relatively high costs associated with radio

tracer production and administration.

Safety and risk

• Nuclear medicine is not safe for the use of human beings, so therefore should not be used on healthy people.

• Also the procedure is not recommended for pregnant women because unborn babies have a greater sensitivity to radiation than children or adults.

Safety and risk

• Radioactive substances are emitted in to the body so the safest way is to use a radio nuclide which has a short half life, so it can decay to a safe level in the fastest possible time.

Safety and risk

• Most of the administered radioactive isotopes is excreted as urine via the kidney and bladder but same is excreted as perspiration and saliva. This means that the patient has radio active substances on their skin and should take extra care when around other people.

Safety and risk

• Safety precautions to be taken when near a patient has been injected with radioactive substance. Wear a pathology gown and disposable gloves also minimise the time spend with the patient and maximise the distance from the patient.

• Evaluates hepatocellular function and patency of the biliary system

• Performed with a variety of compounds that share the common iminodiacetate moiety

• Although it is an excellent test to decide whether the common bile and cystic ducts are patent, biliary scintigraphy does not identify gall stones or give any anatomic information

Hepato biliary Imaging

Red: A lipophilic component

Blue : A polar component

• HIDA - Little used today• DISIDA (Disofenin) -85% extracted by

the hepatocytes• BRIDA (Mebrofenin) -98% extracted

by the hepatocytes

IDA Derivatives

• The lipophilic component : binding to hepatocyte receptors for bilirubin

• Transported through the same pathways as bilirubin, except for conjugation

Pathways of IDA derivatives

Normal Study

• Immediate demonstration of Hepatic Parenchyma

• Normal Liver (5 mins),

• Intrahepatic Bile ducts (10-15 mins),

• CBD, GB & Duodenum (15-30 mins),

• Small Intestine (>30 mins)

Filling Phase

Emptying phase

Indications

• Functional assessment of the hepatobiliary system

• Integrity of the hepatobiliary tree– Evaluation of suspected acute

Cholecystitis– Evaluation of suspected chronic biliary

tract disorders– Evaluation of common bile duct

obstruction– Detection of bile extravasation– Evaluation of congenital abnormalities

Contraindications

• Hypersensitivity to– IDA derivative– Local anesthetics of the amide type

• Cardiac arrhythmias• Pregnancy

Acute Cholecystitis

• Investigation of choice is Ultrasound• Most effective investigation is Radionuclide biliary

scanning

• No filling of Gall bladder after 4 hours of injection indicates obstruction

• A normal HIDA scan excludes it. 100% negative predictive value.

Diagnostic test Sensitivity Specificity

Ultra sound 85% 95%

Tc HIDA scan 95% 95%

Biliary Atresia

Excluded by demonstrating transit of radiotracer into the bowel

Bile Leaks

• Most appropriate non-invasive imaging technique for evaluation of bile leaks

• Sensitivity: 87%, • Specificity: 100%

• Radionuclide imaging of liver and spleen depends on the function common to both i.e, phagocytosis.

• The most commonly used agent is 99m Tc Sulphur colloid.

• In normal scan there is homogenous distribution of 99m Tc Sulphur colloid through out the organ

Liver & Spleen

SMALL INFARCTING SPLEEN

99mTc COLLOID STUDY AFTER SPLEENECTOMYSHOWING VIABLE AND FUNCTONING SPLENIC TISSUE IN THE OMENTUM

LIVLIVER SECONDARIESER SECONDARIES

Tc SULPHUR COLLOID –KUPFER CELLS

Tc HIDA HEPATOCYTES

• The Meckel ’s scan is performed by giving Tc Pertechnetate , which is taken up by the ectopic gastric mucosa in the diverticulum and localized with scintigraphy

• The diagnosis of Meckel’s diverticulum is difficult.

• Plain abdominal radiographs, CT, US are rarely helpful.

Meckel’s Scan

Meckel’s in Children

• Single most accurate diagnostic test for Meckel’s is scintigraphy with Tc Pertechnetate

• Its preferentially taken up by the mucus secreting cells of gastric mucosa and ectopic gastric tissue in the diverticulum

Meckel’s in Adults

• As ectopic gastric mucosa is reduced, agents like pentagastrin, glucagon and cimetidine are used

• Pentagastrin indirectly increases the metabolism of mucus producing cells

• Glucagon inhibits peristaltic dilution and washout of intraluminal radionuclide

• Cimetidine decreases the peptic secretion and therefore retards the release of pertechnetate from the diverticular lumen, thus resulting in higher radionuclide concentrations in wall of diverticulum

NORMAL STUDY

WITHOUT H2 BLOCKADE SO TRACER IS SEEN IN THE INTESTINAL LUMEN DUE TO GASTRIC SECRETION OF THE TRACER.

MECKEL”S DIVERTICULUM IN THE RIGHT SIDE OF THE PELVIS

Normal Study

Achalasia

Achalasia

GI Bleed

• Tc labeled RBC is the most sensitive but least accurate method for localization of GI bleeding

• With this technique, the patient’s own RBC s are labeled and reinjected.

• The labeled blood is extravasated into the GI tract lumen, creating a focus that can be detected scintigraphically.

• Multiple images are collected over 24 hours

GI Bleed

• The tagged RBC scan can detect bleeding as slow as 0.1 ml/ min

• Unfortunately, spatial resolution is lacking, and blood may move retrograde in the colon or distally in the small bowel.

• If RBC scan is negative, angiography is unlikely to be revealing. Thus its used as a guide to the utility of angiography

INDICATIONS1. RECURRENT BLEEDING2. ENDOSCOPY IS

INCONCLUSIVE3. COMORBIDITIES

99mTc COLLOID99mTc RBC

Renal System

The main tracers used in evaluation of the kidney:

• DMSA : Di Mercapto Succinic Acid

• DTPA : Di-ethylene Tri-amine Penta-Acetic acid

• MAG3 : Mercapto Acetyl triGlycine

99mTc-DMSA :

• 99mTc-DMSA is cleared by both filtration and secretion, but the clearance is relatively complex and it does bind to parenchymal tissues.

• It is useful as a renal cortical imaging agent.

99mTc-DTPA:

• 99mTc-DTPA is primarily a glomerular filtration agent.

• It is also useful for evaluation of obstruction and renal function.

• It is less useful in patients with renal failure.

99m Tc-MAG3:

• 99m Tc-MAG3 is cleared by tubular secretion, and no glomerular filtration occurs.

• The tracer is well suited for evaluation of renal function and diuretic scintigraphy

• Also, it is an excellent tracer to evaluate renal plasma flow.

Procedure

• After a bolus injection of the tracer, images are obtained that can be used to estimate relative renal function.

• When the tracer reaches the collecting system, a diuretic is given and half-life is calculated based on the slope of the curve in response to the diuretic.

Renal Cortical Scintigraphy

• Done with 99mTc-DMSA

• Acute infection can produce abnormalities in the scan; and if the test is being performed to evaluate for cortical scarring, it should be done at least 3 months after an acute infection

Image of the kidneys obtained 3 hours after administration of 99mTc-DMSA shows that the left kidney is decreased in size, and contains several focal cortical defects, most notably at both poles.

Diuretic Scintigraphy:

• Diuretic scintigraphy is performed with DTPA or MAG3.

• MAG3 is more useful in patients with renal insufficiency, but DTPA is more economical.

• Diuretic scinitigraphy offers a quantitative assessment of obstruction and does not require an invasive procedure, intravenous iodinated contrast medium, or anesthesia.

Dynamic function images over 40 minutes demonstrate good uptake of tracer by both kidneys & prompt visualization of the collecting systems. A slight relative delay in clearance from the right kidney is noted.

Horse Shoe Kidney

Ectopic Kidney

Radioactive Iodine Uptake test

• Is less widely used because of more precise biochemical measurements of T3 T4 TSH

• This test in the past involved oral administration of Iodine 123

• A normal result is 15-30% uptake of the radionuclide after about 24 hours.

• Use of Iodine 123 is preferable over Iodine 131(8 days) because of a shorter half life(12 hours) and lesser radiation exposure

Thyroid - scintigraphy

99m PERTECHNETATETrapped but not organifiedCompetes with iodide for uptakeCheap and readily available

IODINE (123I or 131 I)Trapped and organifiedBetter for retrosternal goitresExpensive, cyclotron generated

NORMAL THYROID UPTAKE

COLD NODULE

HOT NODULE

• 20% of cold nodules are Malignant• 5% of hot nodules are Malignant

• Thus routine isotope scanning is no longer used to distinguish Benign from Malignant

Mechanism of ActionRadioiodine nuclide release energy beta & gamma

• I 131 ablates principally due to the short range beta radiation. It destroys cells at the end of their path

• The accompanying high energy penetrating Gamma ray radiation mostly escapes the patient producing unwanted radiation fields

Indications for Thyroid Scintigraphy

1. Thyroid nodules2. Thyrotoxicosis3. Goiter4. Ectopic thyroid5. Thyroid cancer6. Retrosternal mass7. Work up of neonates with low T4 and/or high TSH8. Occult thyroid malignancy9. Metastasis10.Swellings in thyroid region

ContraindicationsAbsolute

1. Pregnancy

2. Breastfeeding

Relative

1. Bone marrow depression

2. Pulmonary function restriction.

3. Salivary gland function restriction.

4. Presence of neurological symptoms.

Short-term complications

• Radiation thyroiditis(transient)• Sialadenitis • Gastritis 30% • Bone marrow depression• Xerostomia• Nausea/vomiting • Hypospermia

Long-term complications

• Radiation pulmonary fibrosis• Permanent bone marrow depression• Chronic hypospermia or azoospermia• Early onset of menopause• Chronic dry eye• Hypoparathyroidism (rare and

transient)

Ectopic Thyroid

Radio Iodine Ablation

GravesThyroid cancer

Graves disease

• RAI has been used since 1940 (more than 50 years) for treating thyroid disease

• High rate of success with permanent cures affected and few undesirable effects for hyperthyroid & thyroid cancer

• The majority of patient receive anti thyroid drug but the success rate is limited

• Anti thyroid therapy failed, prime candidate for radioiodine therapy

Tc 99m PertechnetateThyroid scintigram

• Symmetrically enlarged gland

• Homogenous tracer distribution uniform uptake without nodularity(occasionally cold nodule seen)

• Prominent pyramidal lobe

GRAVES DISEASE

AUTONOMOUS NODULE

MNG WITH HYPERACTIVE NODULES

SOLITARY COLD NODULES

115

Treatment• 3 option :

– medical therapy antithyroid drugs– radioactive iodine– surgery thyroidectomy, partial or

complete surgical• None is the best treatment• USA radioactive is the first choice

(69%)

Percentage relapse of hyperthyroidism

Cure rate

• 59.1 % (6th month)• 72.7 % (12th month)• 92.0% (24th month)

• Return to normal T4 Take 2-6 months• During interval May need to continue

antithyroid drugs • Monitored Hypothyroidism and recurrent

hyperthyroidism • There is no optimal dose for RAI ~

controversial• Goals for RAI treatment vary from

inducing hypothyroidism to restoring euthyroidism

Before radioiodine therapy :

• Stop Antithyroid drugs 3-4 wks before

• Shall not have iodine containing injection/tablets for 4 months

• Patient have to fast overnight & an hour afterwards

Take home message (Graves)

• Iodine-131 therapy has been available for over 50 years

• There is no standard treatment for Graves’ hyperthyroidism (medical, surgical and radioactive iodine)

• RAI is Proven to be save, effective and economical form of treatment for thyroid diseases

• Appropriate patient selection & explanation the expected outcomes are essential

Radio Iodine Ablation

GravesThyroid cancer

Thyroid cancer

• Incidence of thyroid cancer is increasing --Mortality rate of 2-5%

--Recurrence rate post-lobectomy 5% - 20%

• No doubt that surgery is the primary treatment

Total thyroidectomy is the choice

• Surgery alone has remained inadequate to ensure complete cure

RAI Decreased recurrence and death rates in the following ways:1.Destroyed remaining normal thyroid tissue2.Destroys occult microscopic cancer3.The use of higher doses of I-131 treatment

permits post-ablative total body scanning

RESIDUAL CA THYROID TISSUE

METASTASIS IN CERVICAL &MEDIASTINAL LN

• Follicular thyroid cancer demonstrate a capability of taking up iodine, although less than that of normal thyroid cells.

• 50% of papillary carcinomas are also able to take up iodine and the presence of follicular elements on histology is an indicator of iodine uptake capabilities.

• Medullary, anaplastic carcinomas and lymphomas of the thyroid do not take up I-131, which therefore has no role in therapy following ablation of remnant thyroid tissue.

• Medullary thyroid cancer could be treated with I-131 MIBG (metaiodobenzylguanidine)

Optimal dose

• Ablation dose : 30 – 200 mCi • Metastatic lesions : 150 – 300 mCi • Conservative approach 150 mCi• Repeated treatments were given

but not exceeding a cumulative dose of 1000 mCi

Elimination

• I 131 leaves through saliva, sweat, blood, urine, faeces

• Majority of administered RAI has been extracted after 48 hours

Near / total thyroidectomy

Thyroid / whole body scan

Positive Negative

Radio ablation80-100 mCi

Hormone substitution/suppression

• Tg• Whole body scan

Positive Negative

Radioiodine therapy100-150 mCi

4-6 week post-surgery

5 months 1 month hormone off

Survival rate :• 91% (322 patients) up to 15 yrs • 90-100% up to 7 yrs with or without local or regional metastases

Preventive ablation

Key to success in thyroid Cancer

• Early detection• Adequate thyroidectomy• Post operative radioiodine therapy• Meticulous follow-up surveillance

Take home message( Ca Thyroid)

• Radioactive Iodine recommended as an adjunctive therapy (ablation / preventive) for thyroid cancer after thyroidectomy for the complete management of well-differentiated thyroid cancer

• External beam radiotherapy for Anaplastic ca

• Radiation exposure after a latent period of 30 years can cause Papillary cancer

• RIA is best for Follicular cancer

Future Trends

• Monoclonal antibodies or their fragments are potentially ideal vehicles to carry radioisotopes to specific sites within the body

• But radiolabel has to be inserted without affecting the binding site

Thank you…

Radionuclide imaging

Health & Medicine

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