Contributions of Nuclear Isotopes in Medicine, a Perspective

Transcription

1 Contributions of Nuclear Isotopes in Medicine, a Perspective February 21, 2012 at American Nuclear Society, CT Section David W. Cheng, MD, PhD Associate Professor of Diagnostic Radiology Chief of Nuclear Medicine Medical Director of Yale PET Center

2 Basic Principles Basic physics in Nuclear Medicine how are the signals generated ( -rays and characteristic x-rays) Radiation detection and instrumentation probe (for counting) and scanners for imaging Nuclear pharmacy radio-pharmaceutical production (sterile, pyrogen-free, purity) Biodistribution and pathophysiology chemical property dictates the pattern of uptake

3 Properties of an atom A Z X X = name of element A = atomic mass Z = atomic number

4 Physical constants Charge = x coulomb Rest mass of proton = 1.67 x grams Rest mass of electron = 9.11 x grams 1 electron volt (ev) = x erg 1 calorie (cal) = 4.18 x 10 7 erg 1 angstrom (A) = meter 1 Curie = 3.7 x Bq (or dps)

5 Mass-Energy Equivalence Particle Mass (A.U.) Energy (MeV) electron 54x proton neutron

6 Concept of Half-life (t 1/2 ) physical t 1/2 = time required for the number of radioactive atoms in a sample to decrease by 50% biological t 1/2 = biological clearance of radionuclide from a particular tissue or organ by 50% effective t 1/2 = actual half-life of the entire biological system: = + t 1/2eff t 1/2p t 1/2b

7 Schematic of Anger Camera (Hal Anger, 1957)

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13 Multichannel Analysis Photon Energy (kev)

14 Comparative Spectrums of Tc-99m & Co kev 140 kev Channel Number Co-57 Tc-99m

15 Cardiovascular Scintigraphy Common radiopharmaceutical Thallium-201 chloride (Tl-201) t 1/2p = 73 hours, photopeak = kev (95%) First pass extraction = 88% under normal flow Redistribution Tc-99m Sestamibi (isonitrile, mono-cation) t 1/2p = 6 hours, photopeak = 140 kev (89%) First pass extraction = half of Tl-201 t 1/2eff > 5 hours in myocardium, no redistribution Tc-99m tetrafosmin MUGA with Tc-99m RBC

16 Skeletal System Tc-99m MDP: bone metastases, acute fractures, osteomyelitis, osteonecrosis (AVN), Paget s disease, prosthesis evaluation Tc-99m sulfur colloid: bone marrow, portal hypertension, hypersplenism In-111 or Tc-99m WBC: osteomyelitis versus cellulitis, fever of unknown origin Ga-67 citrate: osteomyelitis, fever of unknown origin, sarcoidosis, tumors

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20 Characteristics of Gallium Group III element and serves as an iron analog (Fe 3+ ) Circulates in the blood bound to transferrin Accumulates due to increased blood flow and vascular permeability Lactoferrin is released by leukocytes (mostly by neutrophils) at inflammtory site, which outcompetes transferrin for Ga 3+

21 Biodistribution of Gallium Firmly binds to infection site by hours Renal excretion = 15-25% Colon excretion is the major route Biologic t 1/2 = 25 days, Physical t 1/2 =78 h (Ga-67) Pattern can be altered by high iron pool, e.g. multiple blood transfusions and recent gadolinium exposure (from MRI)

22 Applications of Gallium Scans Inflammation or infection in soft tissue and skeleton Sarcoidosis, Sjogren s syndrome Tumor imaging More sensitive above the diaphragm Has been largely replaced by FDG-PET scanning

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24 In-111 Leukocyte Scan Mechanisms of action chemotaxis (attractant) and diapedesis (phagocytosis) Inhibited by corticosteroid use Normal CBC contains 55-65% neutrophils and 25-35% lymphocytes Neutrophils circulate for 5-9 hours (only 2-3% reside in circulating blood) Lymphocytes accumulate during chronic phase

25 Optimal labeling criteria Leukocyte count >5000/mm 3 with minimum being 3000/mm 3 50 cc is drawn to ensure sufficient number of leukocytes (20-30 cc for children) In vitro labeling takes 2 hours In-111 binds to nuclear and cytoplasmic proteins Labeling efficiency is 75-90%

26 Biodistribution of labeled WBC Initially, it is seen in the lungs due to cellular activation from the process At 4 hours after re-infusion, lung activity and blood pool should decrease At 24 hours, spleen > liver > bone marrow The critical organ is the spleen (20 rad/500 uci) for In-111 Large intestine for Tc-99m (3.6 rad/10 mci)

27 Tc-99m Leukocyte

28 In-111 WBC with colitis on CT

29 Pulmonary System Ventilation agents: Xe-133 (t 1/2p =5.2 days, 81 kev, 36.5%) Xe-127 (t 1/2p =36.4 days, 172, 203, 375 kev) Rb-81/Kr-81m (t 1/2p = 13 seconds, 190 kev), generator is good only for 1 day Tc-99m DTPA aerosol particulate ( m in size) Perfusion agents: Tc-99m MAA (10-50 m in size, k particles or <1% of normal vascular bed)

30 V/Q Scan

31 Hepatobiliary System HIDA scan (iminodiacetic acid) for acute and chronic cholecystitis, biliary atresia Lidofenin (dimethyl IDA) - 84% hepatic uptake Disofenin (disopropyl IDA) - 88% uptake competes well up to 10 mg/dl bilirubin Mebrofenin (bromotriethyl IDA) - 98% uptake competes well up to 28 mg/dl bilirubin Tc-99m sulfur colloid for liver-spleen imaging Tc-99m RBC for hemangioma versus tumor

32 HIDA Scan

33 Quantitative HIDA Scan

34 Gastrointestinal System Gastrointestinal bleeding - Tc-99m RBC can detect slow bleed at ml/min Gastric emptying - Tc-99m sulfur colloid mixed with standardized diet Ectopic gastric mucosa - Tc-99m TcO 4 - Meckel s diverticulum Cimetidine - inhibits release Glucagon - antiperistaltic effect delays washout Pentagastrin - increases uptake and duration of uptake Helicobacter Pylori - C-14 urea breath test Malabsorption - Co-57/Co-60 cobalamin Schilling test Tc-99m human serum albumin for protein losing enteropathy

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36 Endocrine System Thyroid benign I-123 (t 1/2p =13.2 hrs, 159 kev, 83.4%) for uptake and imaging g Tc-99m for imaging only (symporter without organification information) I-131 (t 1/2p =8.1 days, 364 kev, 81%) for uptake and imaging

37 Cold thyroid nodule

38 Graves Disease

39 Multinodular Goiter

40 Endocrine System (cont d) Papillary carcinoma % of welldifferentiated thyroid cancers, metastasizes mostly via lymphatic system but also via hematogenous to lungs Follicular carcinoma % of welldifferentiated thyroid cancers, metastasizes via hematogenously to skeleton Hurthle cell - a variant of follicular carcinoma Medullary - parafollicular C cells

41 29 y.o. female with papillary CA

42 52 y.o. female with BRAF(+) follicular variant papillary CA

43 41 y.o. male with 3 cm papillary CA

44 Parathyroid Imaging Subtraction imaging with Tl-201 chloride/tc-99m pertechnetate Sensitivity reported to be 85-95% for larger primary adenomas (300 mg) Tc-99m Sestamibi/I-123 subtraction imaging 2 day protocol with I-123 given the first day Tc-99m Sestamibi only Planar and SPECT imaging at 15 and 120 minutes postinjection Sensitivity at Yale has been 75-80%

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46 PET/CT Discovery LS 16 Discovery ST 4 Fixed & Mobile

47 Positron Emission Tomography Positron = anti-matter of an electron Conservation of mass law (E=mc 2 ) yields 511 kev x 2 photons diametrically (at 180 o apart coincidence photons) Detector material has to be more dense to increase the capture ratio (e.g. BGO, LSO, GSO, LySO crystal)

48 Detector Ring 13 51KV E 2 51KV P A PET Training Positron Emitter - nuclear decay produces a positron Positron travels short distance and annihilates with electron Annihilation process produces two photons Each at 511KeV Photons emitted 180 o apart Simultaneous detection of the two 511KeV photons produces a coincidence pair. Count of each coincidence pair stored as Sinogram (Raw Data) Sinogram reconstructed to produce activity based transaxial slice

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50 Coincidence Detection

51 Common PET Radiopharmaceuticals Rb-82m (t 1/2p =75 sec, E max =3.35 MeV): eluted from a portable Sr 82 Cl(t 1/2p =25.5 days)/rb 82 Cl/Kr 82 Cl generator O-15 (t 1/2p =2.07 min, 99.9%, E max =1.72 MeV, range max =8.2 mm H 2 O): H 2 O 15 N-13 (t 1/2p =9.96 min, 100%, E max =1.19 MeV, range max =5.39 mm H 2 O): N 13 H 3 C-11 (t 1/2p =20.4 min, 99+%, E max =0.96 MeV, range max =4.108 mm H 2 O): C 11 -neuroreceptors F-18 (t 1/2p =109.7 min, 97%, E max =0.635 MeV, range max =2.39 mm H 2 O): F 18 DG

52 Detector Ring 13 51KV E 2 51KV P A PET Training Positron Emitter - nuclear decay produces a positron Positron travels short distance and annihilates with electron Annihilation process produces two photons Each at 511KeV Photons emitted 180 o apart Simultaneous detection of the two 511KeV photons produces a coincidence pair. Count of each coincidence pair stored as Sinogram (Raw Data) Sinogram reconstructed to produce activity based transaxial slice

53 2-Fluoro-2-DeoxyGlucose F-18 FDG is taken up like glucose by tissues at a rate proportional to demand for glucose Phosphorylated and then trapped intracellular Radionuclide (F-18) releases a positron whose annihilation photons can be detected Coincidence detection will lower interference from random photons in the vicinity

54 FDG accumulation other characteristics of tumor cells increased level of hexokinase decreased level of glucose-6-phosphatase in combination with increased transport capacity, FDG retention has a more favorable environment within a tumor cell (Smith, TA. Nucl Med Commun 19:97-105, 1998)

55 Intravascular [glucose] plasma Tissue hexokinase [glucose] intracellular [glucose-6-p] phosphatase glycolysis [FDG] plasma [FDG] intracellular hexokinase phosphatase [FDG-6-P]

56 FDG-PET Imaging

57 Lung Cancer Staging FDG PET Sensitivity: 83% Specificity: 92% CT Sensitivity: 57-64% Specificity: 74-85% J Nucl Med 2001;42:1S-93S

58 Non Small Cell Lung Cancer

59 Lymphoma Staging FDG PET Sensitivity: 87% Specificity: 93% CT Sensitivity: 92% Specificity: 10% J Nucl Med 2001;42:1S-93S

60 Lymphoma

61 Head & Neck Cancer Staging FDG PET Sensitivity: 84-87% Specificity: 89-95% CT Sensitivity: 62-77% Specificity: 73-87% J Nucl Med 2001;42:1S-93S

62 Squamous Cell CA of Tongue and NSCLC

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64 Colorectal Cancer Recurrence FDG PET Sensitivity: 93% Specificity: 87% CT Sensitivity: 79% Specificity: 73% J Nucl Med 2001;42:1S-93S

65 Rectal CA

66 Breast Cancer Staging FDG PET Sensitivity: 91-95% 95% Specificity: 88% CT Sensitivity: 63% Specificity: 96% J Nucl Med 2001;42:1S-93S

67 Internal Mammary Lymph Node

68 Acetabular MET: Breast CA

69 Melanoma Staging FDG PET Sensitivity: 83% Specificity: 91% CT Sensitivity: 88% Specificity: 75% J Nucl Med 2001;42:1S-93S

70 Melanoma

71 SUV= standard uptake value MRglc = {([glc]/100) C(t)/(dose/body weight)} LC (b/100) MRglc = glucose utilization rate in tissue [glc] = glucose concentration in arterial plasma (mg/dl) C(t)* = radioactivity concentration in tissue dose = dose injected LC = lump constant b = assumed to be a constant * Works better if t > 45 minutes post-injection

72 Therapy: bone pain palliation [Sr-89]Cl (t 1/2p = 50.5 days, t 1/2b = 14 days) Bioavailability = 50% of injected dose max =1.46 MeV (max. range = 8 mm in tissue) Typical dosing 16 Ci/kg to 10.8 mci/kg or empiric total dose of 4-5 mci for adults Blood count nadir = 4-8 weeks Recommend platelet >60k and WBC >2.4k before therapy

73 Therapy: bone pain palliation [Sm-153] Ethylene Diamine Tetramethylene Phosphonate (EDTMP) or Quadramet t 1/2p = 47 hours (1.93 days) Typical dosing: 0.5 mci/kg to 2 mci/kg -emission: 103 kev (29%) -emissions: 640 kev (30%), 710 kev (50%), and 810 kev (20%) Maximum range = 3.0 mm in tissue Average range = 0.5 mm in tissue

74 Radioimmunotherapy: Bexxar [I-131] Tositumomab (MW 150 kd, t 1/2p = 8 days) murine IgG 2a anti-cd20 antibody -emission: 364 kev (82%) -emission: 606 kev maximum (89%) with range = 2 mm in tissue Covalently linked Dosing: maximum 88 cgy total body Typically at 75 cgy if platelet >150k Reduced to 65 cgy if 100k> platelet <150k

75 Radioimmunotherapy: Zevalin [Y-90] Ibritumomab tiuxetan- murine IgG 1 anti-cd20 antibody (t 1/2p = 64 hours) -emission only: MeV Range = 11 mm (max) and 2.5 mm (avg) in tissue Chelation of yttrium-90 Dosing: 0.4 mci/kg if platelet >150k 0.3 mci/kg if 100k> platelet <150k up to 32 mci maximum

76 Therapy: Sirtex Sphere [Y-90]Microspheres to be administered directly into hepatic circulation for treatment of hepatocellular carcinoma or hepatic metastatic lesions m / 22k-73k particles Dosimetry is estimated using Tc-99m macroalbumin aggregate mapping and dedicated software Dosing: Gy to the liver