1. Biodistribution of Radiopharmaceuticals Jim Corley, RPh, MS, BCNP Medical College of Georgia

2. Biodistribution of Radiopharmaceuticals l Properties of a Radioactive Element That Determine Tissue Localization and Excretion. l Determinants of Localization of Radioactive Drugs l Determinants of Renal Excretion

3. Properties of a Radioactive Element That Determine Tissue Localization and Excretion

4. l Oxidation state at physiologic pH l Solubility of the stable state l Tendency toward incorporation into organic compounds l Tendency to be chelated or to form protein complexes in circulation or in a particular tissue Chief Determinants of Biological Localization

5. Oxidation State, Ionic Size and Charge _ I - 2.15 Å _ TcO 4 - 1.99 Å K + 1.33 Å Tl + 1.40 Å ++ _ ClO 4 - 1.74 Å

6. Group I: THE ALKALI METALS

7. l Element Na K Rb Cs l Subgroup I Cu Ag Au l Principle Location Muscle Liver Protein Liver Principle Excretion Urine Feces Urine

8. Group II: Alkaline Earths

9. Group II: THE ALKALINE EARTHS l Element Be Mg Ca Sr Ba Ra l Subgroup II Zn Cd Hg l Principle Location Bone Liver Kidney Pediatric Nuclear Medicine 1974 l Principle Excretion Urine - Feces Urine & Feces - Feces

10. Group III: Lanthanides & Actinides

11. Group III: THE LANTHANIDES & ACTINIDES l Element B Al Ga In Tl l Subgroup III Sc Y La l Principle Location No radioisotopes available Bone, muscle Bone, liver Muscle Bone, liver Bone Liver l Principle Excretion - Feces Urine Urine & feces

12. Rare Earths

13. RARE EARTHS l Element Ce Pr Nd Pm Sm Eu Gd Tb Dy Ho Er Tm Yb Lu l Principle Location Liver, bone Bone, liver Bone l Principle Excretion Feces & Urine Urine

14. Group IV

15. l Element C Si Ge Sn Pb l Subgroup IV Ti Zr Hf l Principle Location - Bone, liver Bone - Bone Liver, bone Pediatric Nuclear Medicine 1974 l Principle Excretion - Urine Urine & Feces - Feces Feces & Urine

16. Group V

17. l Element N P As Sb Bi Subgroup V V Nb Ta l Principle Location - Muscle, bone Blood Bi Liver, kidney, bone Pediatric Nuclear Medicine 1974 l Principle Excretion - Urine Urine & Feces Urine

18. Group VI

19. l Element O S Se Te Po l Subgroup VI Cr Mo W l Principle Location - Blood Blood, liver, kidney Bone, blood Liver Bone Pediatric Nuclear Medicine 1974 Principle Excretion - Urine - Urine

20. Group VII: Halogens

21. Group VII: THE HALOGENS l Element F Cl Br I At l Subgroup VII Mn Tc Re l Principle Location Bone - Liver, GI tract Thyroid GI tract Liver GI tract Pediatric Nuclear Medicine 1974 Principle Excretion Urine - Urine Feces Urine

22. Group VIII: Platinum Metals

23. Group VIII: THE PLATINUM METALS l Element Fe Ru Os Co Rh Ir Ni Pd Pt l Principle Location Blood, liver Muscle General Liver Muscle Liver - Liver, kidney Liver,muscle,kidney Pediatric Nuclear Medicine 1974 Principle Excretion Feces Urine - Urine Urine & Feces

24. Useful Positron Isotopes C-11N-13O-15F-18Ga-68Rb-81

25. l Properties of a Radioactive Element That Determine Tissue Localization and Excretion l Determinants of Localization of Radioactive Drugs l Determinants of Renal Excretion Biodistribution of Radiopharmaceuticals

26. Determinants of Localization of Radioactive Drugs Determinants of Localization of Radioactive Drugs A. Organ characteristics B. Drug characteristics B. Drug characteristics Biodistribution of Radiopharmaceuticals

27. Determinants of Localization of Radioactive Drugs A. Organ characteristics Relative Blood Flow to the organ Types of capillaries in the organ Capillary "density" or number per unit volume of tissue Specific drug-receptor sites

28. Determinants of Localization of Radioactive Drugs B. Drug characteristics B. Drug characteristics Molecular size and shape Degree and strength of binding to plasma proteins Lipid solubility Specific drug receptor and transport mechanisms Biodistribution of Radiopharmaceuticals

29. Chemical Structures Influencing Lipid Solubility DecreaseIncrease Hydrophilic GroupsHydrophobic Groups -OHAromatic Rings -COOHCH3 -C=O-C2H5 -PO4, -P2O7-C=C- -NH2-Cl -SOOH, -SOONH2-I -OCH3-SH

30. Mechanisms of Localization lActive Transport lPhagocytosis lCell Sequestration lCapillary Blockade lSimple or Exchange Diffusion lCompartmental Localization lMetabolic Substitution Pediatric Nuclear Medicine 1974

31. Active Transport Thyroid scanning with iodide or pertechnetate Renal scanning with Iodohippurate Liver scanning with HIDA Pancreatic scanning with Selenomethionine Pediatric Nuclear Medicine 1974 Mechanisms of Localization

32. Active Transport - Thyroid scanning with iodide or pertechnetate l 43 year old female l Exophthalmus l Agitated l elevated free T4 l undetectable TSH l Tc-99m pertechnetate scan l RAIU 66% l Treatment 7.3mCi NaI-131

33. Active Transport - Liver scanning with HIDA

34. Mechanisms of Localization Phagocytosis Liver scanning with colloids Spleen scanning with colloids or heat damaged red blood cells Bone marrow scanning with micro-colloids Pediatric Nuclear Medicine 1974

35. Phagocytosis - Colloids

36. Phagocytosis - Liver scanning with colloids

37. Cell Sequestration Spleen counting with heat or disease damaged red blood cells (Cr-51 or Tc-99m) Capillary Blockade Lung scanning with Tc-99m labeled human serum albumin (MAA) Pediatric Nuclear Medicine 1974 Mechanisms of Localization

38. Spleen scanning with colloids or heat damaged red blood cells

39. Simple or Exchange Diffusion Bone scanning with F-18 or Tc-99m phosphonates Brain scanning with Tc-99m pertechnetate or DTPA Mechanisms of Localization

40. Bone Agents Structure PyrophosphateMDPHDP

41. Types of Bone Scans Whole Body Limited Three-phase Whole Body Limited Three-phase

42. Brain scanning with Tc-99m pertechnetate or DTPA Normal

43. Brain scanning with Tc-99m pertechnetate or DTPA Brain Death

44. Compartmental Localization Blood pool scanning of heart and vascular system with Tc-99m RBC or HSA Cerebrospinal fluid space with In-111 DTPA Mechanisms of Localization

45. CSF Leak Posterior Nasal Pharynx Cerebrospinal fluid space with In-111 DTPA

47. Metabolic Substitution F-18 Fluorodeoxyglucose (FDG) Imaging for Cancer, Brain, Heart Mechanisms of Localization l Molecular Formula C 6 H 11 18 FO 4 l Molecular Weight 166.15 daltons l Half life 110 min l D-glucose C 6 H 12 O 6 l M.W.= 180.16 dal

48. F-18 FDG Imaging for Cancer - Lymphoma

49. F-18 FDG Imaging for Heart - Ischemia Ischemia or Infarct Lateral Wall

50. F-18 FDG Imaging for Heart - Ischemia Reversible Ischemia Lateral Wall

51. F-18 FDG Imaging for Brain - Lymphoma

52. Properties of a Radioactive Element That Determine Tissue Localization and Excretion Determinants of Localization of Radioactive Drugs Determinants of Renal Excretion Biodistribution of Radiopharmaceuticals

53. Determinants of Renal Excretion A. Active renal tubular transport - many organic acids & some organic bases are actively excreted by the renal tubules B. Molecular size - unbound substances with molecular weight < 40,000 are eliminated by glomerular filtration C. Plasma protein binding - substances tightly bound to plasma proteins are not filtered by the glomeruli D. Lipid solubility - lipid-soluble drugs tend to be reabsorbed by the renal tubules and are not excreted Biodistribution of Radiopharmaceuticals

54. Acknowledgment l Mallinckrodt Nuclear Medicine Teaching Files l http://gamma.wustl.edu/home.html http://gamma.wustl.edu/home.html