Biodistribution of Radiopharmaceuticals

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					  Biodistribution of
Radiopharmaceuticals

Jim Corley, RPh, MS, BCNP
Medical College of Georgia
     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
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
             Oxidation State, Ionic
               Size and Charge
       _        _        _
                                   +       +


  I-       TcO4-    ClO4-     K+        Tl+
2.15 Å     1.99 Å   1.74 Å   1.33 Å    1.40 Å
Group I: THE ALKALI METALS
     Group I: THE ALKALI METALS
 Element       Principle   Location   •Principle Excretion
   Na                 Muscle                   Urine
   K                  Muscle                   Urine
   Rb                 Muscle                   Urine
   Cs                 Muscle                   Urine

Subgroup   I

   Cu                  Liver                   Urine
   Ag                 Protein                  Feces
   Au                  Liver                   Urine
Group II: Alkaline Earths
    Group II: THE ALKALINE EARTHS
   Element         Principle Location      Principle Excretion
      Be                   Bone                      Urine
      Mg                                               -
      Ca                   Bone                     Feces
      Sr                   Bone                 Urine & Feces
      Ba                   Bone                 Urine & Feces
      Ra                   Bone                 Urine & Feces
Subgroup   II

     Zn                    Liver                        -
     Cd                    Liver                      Feces
     Hg                   Kidney                      Feces
                                          Pediatric Nuclear Medicine 1974
Group III: Lanthanides & Actinides
     Group III: THE LANTHANIDES & ACTINIDES
    Element      PrincipleLocation    Principle   Excretion
        B            No radioisotopes                -
                         available
       Al            No radioisotopes                -
                         available
      Ga               Bone, muscle            Feces
       In               Bone, liver            Feces
       Tl                Muscle                Feces
Subgroup   III

      Sc                 Bone, liver            Feces
      Y                    Bone                 Urine
      La                   Liver            Urine & feces
Rare Earths
                  RARE EARTHS
   Element      Principle Location      Principle Excretion
     Ce              Liver, bone            Feces & Urine
      Pr             Liver, bone            Feces & Urine
     Nd              Liver, bone            Feces & Urine
     Pm              Liver, bone            Feces & Urine
     Sm              Liver, bone            Feces & Urine
     Eu              Liver, bone            Feces & Urine
     Gd              Bone, liver                 Urine
     Tb                 Bone                     Urine
     Dy                 Bone                     Urine
     Ho                 Bone                     Urine
      Er                Bone                     Urine
     Tm                 Bone                     Urine
     Yb                 Bone                     Urine
     Lu                 Bone                     Urine
Group IV
                          Group IV
    Element        Principle Location   Principle    Excretion
       C                     -                     -
       Si                    -                     -
      Ge                Bone, liver              Urine
      Sn                  Bone                   Urine
      Pb                  Bone               Urine & Feces

Subgroup   IV

      Ti                    -                      -
      Zr                  Bone                  Feces
      Hf               Liver, bone           Feces & Urine

                                          Pediatric Nuclear Medicine 1974
Group V
                    Group V
 Element    Principle   Location   Principle     Excretion
   N                 -                           -
   P            Muscle, bone                   Urine
   As              Blood                       Urine
   Sb              Blood                       Urine
   Bi                Bi                        Urine
Subgroup V

   V         Liver, kidney, bone        Urine & Feces
   Nb        Liver, kidney, bone        Urine & Feces
   Ta        Liver, kidney, bone            Urine

                                      Pediatric Nuclear Medicine 1974
Group VI
                         Group VI
    Element     Principle   Location   Principle Excretion
       O                   -                       -
       S                   -                       -
      Se               Blood                    Urine
      Te               Blood                    Urine
      Po         Blood, liver, kidney              -

Subgroup   VI

      Cr            Bone, blood                  Urine
      Mo               Liver                     Urine
      W               Bone                       Urine

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

    Mn                  Liver                   Feces
    Tc                 GI tract                 Urine
    Re                 GI tract                 Urine
                                          Pediatric Nuclear Medicine 1974
Group VIII: Platinum Metals
       Group VIII: THE PLATINUM METALS

Element    Principle  Location   Principle Excretion
  Fe            Blood, liver              Feces
  Ru              Muscle                  Urine
  Os              General                 Urine
  Co               Liver                  Urine
  Rh              Muscle                  Urine
  Ir               Liver                  Urine
  Ni                  -                     -
  Pd           Liver, kidney              Urine
  Pt        Liver,muscle,kidney      Urine & Feces

                                   Pediatric Nuclear Medicine 1974
        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

Determinants of Localization of Radioactive Drugs



A. Organ characteristics



B. Drug characteristics
      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
     Chemical Structures
 Influencing Lipid Solubility
       Decrease             Increase
 Hydrophilic Groups    Hydrophobic Groups
-OH                   Aromatic Rings
-COOH                 CH3
-C=O                  -C2H5
-PO4, -P2O7           -C=C-
-NH2                  -Cl
-SOOH, -SOONH2        -I
-OCH3                 -SH
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
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
        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
                         RES
                                                        Capillary Blockade




        Sulfur Colloid                                        MAA


       True Colloids     Noncolloidal Suspensions



0.01           0.1             1               4    7        10          100
                               Microns
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
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
              Bone Agents Structure




Pyrophosphate               MDP                   HDP
     O         OH           O    H   O            O   OH O

HO   P    O    P    OH HO   P        P    OH HO   P      P    OH

     OH        O            OH   H   OH           OH H   OH
      Types of Bone Scans




Whole Body   Limited   Three-phase
  Brain scanning with Tc-99m
  pertechnetate or DTPA



Normal
   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
    Cerebrospinal fluid space with In-111 DTPA




  CSF
  Leak
Posterior
 Nasal
Pharynx
Cerebrospinal fluid space with In-111 DTPA
Mechanisms of Localization
       Metabolic Substitution
  F-18 Fluorodeoxyglucose (FDG)
  Imaging for Cancer, Brain, Heart
                   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
         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
Acknowledgment

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

				
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