Radionuclide imaging

Radionuclide imaging

1. SUDARSAN AGARWAL [email protected] PINNAMANENI MEDICAL COLLEGE, VIJAYAWADA R adio nuclide Imaging & Its Applications

2. Atom

3. Atom

4. Electromagnetic Spectrum

5. 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

6. Types of Ionizing Radiation Alpha Particles Stopped by a sheet of paper Beta Particles Stopped by a layer of clothing or less than an inch of a substance (e.g. plastic) Gamma Rays Stopped by inches to feet of concrete or less than an inch of lead Radiation Source

7. 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

8. Accurate Diagnosis is key to Surgical practice

9. Accurate Diagnosis is key to Surgical practice X rays , CT Ultra Sound, MRI SPECT , PET

10. MRI SPECT fMRI X-Ray CT Ultrasound

11. 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

12. Hybrid Imaging

13. 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)

14. Radiotherapy x Nuclear Medicine

15. 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

16. 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 )

17. 1. RADIONUCLIDE 2. PHARMACEUTICAL 3. GAMMA CAMERA SPECT

18. 1. RADIONUCLIDE 2. PHARMACEUTICAL 3. GAMMA CAMERA

19. 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

20. 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 .

21. 99m Tc Excited Nucleus Gamma ray 99 Tc Stable Nucleus Photon Decay

22. 1. RADIONUCLIDE 2. PHARMACEUTICAL 3. GAMMA CAMERA

23. 1. RADIONUCLIDE 2. PHARMACEUTICAL 3. GAMMA CAMERA

24. Ideal radiopharmaceutical C heap and readily available Radionuclide easily incorporated without altering biological behavior Radiopharmaceutical easy to prepare Localizes only in organ of interest t 1/2 of elimination from body similar to duration of test

25. 1. RADIONUCLIDE 2. PHARMACEUTICAL 3. GAMMA CAMERA

26. 1. RADIONUCLIDE 2. PHARMACEUTICAL 3. GAMMA CAMERA

27. Gamma Camera A gamma camera consists of three main parts: Electronic systems D etector C ollimator

28. Gamma Camera

29. 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

30. Glucose FDG

31. P lasma C ell T ransport P hosphorylation G lycolysis G lucose 18 F-FDG 18 F-FDG-6-P G lucose-6-P G lycolysis G lucose 18 F-FDG FDG

32. 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

33. 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.

34. 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.

35. 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

36. Arrow points to "dead" myocardial tissue. PET scan of a heart Cardiac Imaging

37. Cerebral Imaging

38. 99m Tc-HMPAO : cross to BBB and fix in the brain proportionally to perfusion 18 FDG : glucose metabolism 99m Tc-TRODAT : dopamine transporter 111 In-DTPA, 99m Tc-DTPA : CSF dynamics, V-P shunt patency study

39. PET image showing malignant breast mass (not revealed by CT , MRI or Mammo ) PET image of same patient with enlarged left axillary lymph nodes

40. 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.

41. Advantages Disadvantages Safety and Risk

42. Advantages Assesses body function and in monitoring flow rate Can measure body composition using dilution analysis. Whole body scanning Response to radiotherapy and chemotherapy

43. 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.

44. 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 .

45. 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 .

46. 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.

47. 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.

48. GIT

49. 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

50. Red: A lipophilic component Blue : A polar component

51. HIDA - Little used today DISIDA ( Disofenin ) - 85% extracted by the hepatocytes BRIDA ( Mebrofenin ) -98 % extracted by the hepatocytes IDA Derivatives

52. The lipophilic component : binding to hepatocyte receptors for bilirubin Transported through the same pathways as bilirubin, except for conjugation Pathways of IDA derivatives

53. Normal Study Immediate demonstration of Hepatic Parenchyma Normal Liver (5 mins), I ntrahepatic Bile ducts (10-15 mins), CBD, GB & D uodenum ( 15-30 mins), Small Intestine (>30 mins)

54. Filling Phase

55. Emptying phase

56. 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

57. Contraindications Hypersensitivity to IDA derivative Local anesthetics of the amide type Cardiac arrhythmias Pregnancy

58. Acute C holecystitis 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%

59. Biliary Atresia Excluded by demonstrating transit of radiotracer into the bowel

60. Bile Leaks Most appropriate non-invasive imaging technique for evaluation of bile leaks Sensitivity: 87%, Specificity : 100%

61. 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

62. SMALL INFARCTING SPLEEN 99mTc COLLOID STUDY AFTER SPLEENECTOMY SHOWING VIABLE AND FUNCTONING SPLENIC TISSUE IN THE OMENTUM

63. LIV LIVER SECONDARIES ER SECONDARIES

64. Tc SULPHUR COLLOID – KUPFER CELLS Tc HIDA HEPATOCYTES

65. 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

66. 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

67. 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

68. NORMAL STUDY

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

70. MECKEL”S DIVERTICULUM IN THE RIGHT SIDE OF THE PELVIS

71. Normal Study Achalasia Achalasia

72. 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

73. 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

74. INDICATIONS RECURRENT BLEEDING ENDOSCOPY IS INCONCLUSIVE COMORBIDITIES 99mTc COLLOID 99mTc RBC

75. Renal System

76. The main tracers used in evaluation of the kidney: DMSA : D i M ercapto S uccinic A cid DTPA : D i-ethylene T ri-amine P enta - A cetic acid MAG3 : M ercapto A cetyl tri G lycine

77. 99m Tc-DMSA : 99m Tc-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.

78. 99m Tc-DTPA: 99m Tc-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.

79. 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 .

80. 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.

81. Renal Cortical Scintigraphy Done with 99m Tc-DMSA A cute 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

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

83. 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 .

84. 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.

85. Horse Shoe Kidney

86. Ectopic Kidney

87. 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

88. Thyroid - scintigraphy 99m PERTECHNETATE Trapped but not organified Competes with iodide for uptake Cheap and readily available IODINE ( 123 I or 131 I) Trapped and organified Better for retrosternal goitres Expensive, cyclotron generated

89. NORMAL THYROID UPTAKE COLD NODULE HOT NODULE

90. 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

91. Mechanism of Action Radioiodine 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

92. Indications for Thyroid S cintigraphy Thyroid nodules Thyrotoxicosis Goiter Ectopic thyroid Thyroid cancer Retrosternal mass Work up of neonates with low T4 and/or high TSH Occult thyroid malignancy Metastasis Swellings in thyroid region

93. Contraindications Absolute 1. Pregnancy 2. Breastfeeding   Relative 1. Bone marrow depression 2. Pulmonary function restriction. 3. Salivary gland function restriction. 4. Presence of neurological symptoms.

94. Short-term complications Radiation thyroiditis (transient ) Sialadenitis Gastritis 30% Bone marrow depression Xerostomia Nausea/vomiting Hypospermia

95. 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 )

96. Ectopic Thyroid

97. Radio Iodine Ablation Graves Thyroid cancer

98. Radio Iodine Ablation Graves Thyroid cancer

99. Graves disease RAI has been used since 1940 (more than 50 years) for treating thyroid disease H igh rate of success with permanent cures affected and few undesirable effects for hyperthyroid & thyroid cancer T he majority of patient receive anti thyroid drug but the success rate is limited Anti thyroid therapy failed, prime candidate for radioiodine therapy

100. Tc 99m Pertechnetate Thyroid scintigram S ymmetrically enlarged gland Homogenous tracer distribution uniform uptake w ithout nodularity(occasionally cold nodule seen) Prominent pyramidal lobe

101. GRAVES DISEASE AUT ON OMOUS NODULE

102. MNG WITH HYPERACTIVE NODULES SOLITARY COLD NODULES

103. 115 Treatment 3 option : medical therapy  antithyroid drugs radioactive iodine surgery  thyroidectomy, partial or complete surgical N one is the best treatment USA  radioactive is the first choice (69%)

104. Percentage relapse of hyperthyroidism

105. Cure rate 59.1 % (6 th month) 72.7 % (12 th month) 92.0% (24 th month )

106. R eturn 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

107. 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

108. 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

109. Radio Iodine Ablation Graves Thyroid cancer

110. Radio Iodine Ablation Graves Thyroid cancer

111. 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

112. RAI Decreased recurrence and death rates in the following ways : Destroyed remaining normal thyroid tissue Destroys occult microscopic cancer The use of higher doses of I-131 treatment permits post-ablative total body scanning

113. RESIDUAL CA THYROID TISSUE METASTASIS IN CERVICAL & MEDIASTINAL LN

114. 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)

115. 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

116. Elimination I 131 leaves through saliva, sweat, blood, urine, faeces Majority of administered RAI has been extracted after 48 hours

117. Near / total thyroidectomy Thyroid / whole body scan Positive Negative Radio ablation 80-100 mCi Hormone substitution/suppression Tg Whole body scan Positive Negative Radioiodine therapy 100-150 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

118. Key to success in thyroid Cancer Early detection Adequate thyroidectomy Post operative radioiodine therapy Meticulous follow-up surveillance

119. 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

120. 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

121. Thank you…