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


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


Properties of a Radioactive Element That Determine Tissue Localization and Excretion :Properties of a Radioactive Element That Determine Tissue Localization and Excretion


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


Oxidation State, Ionic Size and Charge :Oxidation State, Ionic Size and Charge _


Group I: THE ALKALI METALS :Group I: THE ALKALI METALS


Group I: THE ALKALI METALS :Group I: THE ALKALI METALS Element Na K Rb Cs Subgroup I Cu Ag Au Principle Location Muscle Muscle Muscle Muscle Liver Protein Liver Principle Excretion Urine Urine Urine Urine Urine Feces Urine


Group II: Alkaline Earths :Group II: Alkaline Earths


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


Group III: Lanthanides & Actinides :Group III: Lanthanides & Actinides


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


Rare Earths :Rare Earths


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


Group IV :Group IV


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


Group V :Group V


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


Group VI :Group VI


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


Group VII: Halogens :Group VII: Halogens


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


Group VIII: Platinum Metals :Group VIII: Platinum Metals


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


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


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


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


Biodistribution of Radiopharmaceuticals :Biodistribution of Radiopharmaceuticals 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


Biodistribution of Radiopharmaceuticals :Determinants of Localization of Radioactive Drugs 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


Chemical Structures Influencing Lipid Solubility :Chemical Structures Influencing Lipid Solubility


Mechanisms of Localization :Mechanisms of Localization Active Transport Phagocytosis Cell Sequestration Capillary Blockade Simple or Exchange Diffusion Compartmental Localization Metabolic Substitution Pediatric Nuclear Medicine 1974


Mechanisms of Localization :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


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


Active Transport - Liver scanning with HIDA :Active Transport - Liver scanning with HIDA


Mechanisms of Localization :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


Phagocytosis - Colloids :Phagocytosis - Colloids


Phagocytosis - Liver scanning with colloids :Phagocytosis - Liver scanning with colloids


Mechanisms of Localization :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


Spleen scanning with colloids or heat damaged red blood cells :Spleen scanning with colloids or heat damaged red blood cells


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


Bone Agents Structure :Bone Agents Structure Pyrophosphate MDP HDP


Types of Bone Scans :Types of Bone Scans Whole Body Limited Three-phase


Brain scanning with Tc-99m pertechnetate or DTPA :Brain scanning with Tc-99m pertechnetate or DTPA Normal


Brain scanning with Tc-99m pertechnetate or DTPA :Brain scanning with Tc-99m pertechnetate or DTPA Brain Death


Mechanisms of Localization :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


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


: Cerebrospinal fluid space with In-111 DTPA


Mechanisms of Localization :Metabolic Substitution F-18 Fluorodeoxyglucose (FDG) Imaging for Cancer, Brain, Heart Mechanisms of Localization Molecular Formula C6H1118FO4 Molecular Weight 166.15 daltons Half life 110 min D-glucose C6H12O6 M.W.= 180.16 dal


: F-18 FDG Imaging for Cancer - Lymphoma


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


: F-18 FDG Imaging for Heart - Ischemia Reversible Ischemia Lateral Wall


: F-18 FDG Imaging for Brain - Lymphoma


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


Biodistribution of Radiopharmaceuticals :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


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