biodistribution of radiopharmaceuticals

Biodistribution of Biodistribution of RadiopharmaceuticalsRadiopharmaceuticals

Jim Corley, RPh, MS, Jim Corley, RPh, MS, BCNPBCNP

Medical College of Medical College of GeorgiaGeorgia

Biodistribution of Biodistribution of RadiopharmaceuticalsRadiopharmaceuticals Properties of a Radioactive

Element That Determine Tissue Localization and Excretion.

Determinants of Localization of Radioactive Drugs

Determinants of Renal Excretion

Properties of a Properties of a Radioactive Element Radioactive Element

That Determine Tissue That Determine Tissue Localization and Localization and

ExcretionExcretion

Oxidation state at physiologic Oxidation state at physiologic pHpH

Solubility of the stable stateSolubility of the stable state Tendency toward incorporation Tendency toward incorporation

into organic compoundsinto organic compounds Tendency to be chelated or to Tendency to be chelated or to

form protein complexes in form protein complexes in circulation or in a particular circulation or in a particular tissuetissue

Chief Determinants of Chief Determinants of Biological Biological LocalizationLocalization

Oxidation State, Oxidation State, Ionic Size and Ionic Size and

ChargeCharge_

I-

2.15 Å

_

TcO4-

1.99 Å

K+

1.33 Å

Tl+

1.40 Å

+ +_

ClO4-

1.74 Å

Group I: THE ALKALI Group I: THE ALKALI METALSMETALS

Group I: THE ALKALI METALSGroup I: THE ALKALI METALS

Element

NaK

RbCs

Subgroup I

CuAgAu

Principle Location

MuscleMuscleMuscleMuscle

LiverProteinLiver

•Principle Excretion

UrineUrineUrineUrine

UrineFecesUrine

Group II: Alkaline EarthsGroup II: Alkaline Earths

Group II: THE ALKALINE EARTHSGroup 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

KidneyPediatric Nuclear Medicine 1974

Principle Excretion Urine

- Feces

Urine & Feces Urine & Feces Urine & Feces

- Feces Feces

Group III: Lanthanides & Group III: Lanthanides & ActinidesActinides

Group III: THE LANTHANIDES & Group III: THE LANTHANIDES & ACTINIDESACTINIDES Element

B

Al

Ga In Tl

Subgroup III

ScYLa

Principle LocationNo radioisotopes

availableNo radioisotopes

available

Bone, muscleBone, liver

Muscle

Bone, liverBoneLiver

Principle Excretion-

-

FecesFecesFeces

FecesUrine

Urine & feces

Rare EarthsRare Earths

RARE RARE EARTHSEARTHS

ElementCePrNdPmSmEuGdTbDyHoErTmYbLu

Principle Location

Liver, boneLiver, boneLiver, boneLiver, boneLiver, boneLiver, boneBone, liver

BoneBoneBoneBoneBoneBoneBone

Principle ExcretionFeces & UrineFeces & UrineFeces & UrineFeces & UrineFeces & UrineFeces & Urine

UrineUrineUrineUrineUrineUrineUrineUrine

Group IVGroup IV

Group IVGroup IV Element

CSiGeSnPb

Subgroup IV

TiZrHf

Principle Location--

Bone, liverBoneBone

-Bone

Liver, bone

Pediatric Nuclear Medicine 1974

Principle Excretion--

UrineUrine

Urine & Feces

-Feces

Feces & Urine

Group VGroup V

Group VGroup VElement

NP

AsSbBi

Subgroup V

VNbTa

Principle Location-

Muscle, boneBloodBlood

Bi

Liver, kidney, boneLiver, kidney, boneLiver, kidney, bone

Pediatric Nuclear Medicine 1974

Principle Excretion-

UrineUrineUrineUrine

Urine & FecesUrine & Feces

Urine

Group VIGroup VI

Group VIGroup VI Element

OS

SeTePo

Subgroup VI

CrMoW

Principle Location--

BloodBlood

Blood, liver, kidney

Bone, bloodLiverBone

Pediatric Nuclear Medicine 1974

Principle Excretion--

UrineUrine

-

UrineUrineUrine

Group VII: HalogensGroup VII: Halogens

Group VII: THE HALOGENSGroup VII: THE HALOGENS

ElementFClBrI

At

Subgroup VII

MnTcRe

Principle LocationBone

-Liver, GI tract

ThyroidGI tract

LiverGI tractGI tract

Pediatric Nuclear Medicine 1974

Principle ExcretionUrine

-UrineUrineUrine

FecesUrineUrine

Group VIII: Platinum Group VIII: Platinum MetalsMetals

Group VIII: THE PLATINUM METALSGroup VIII: THE PLATINUM METALS

Element

FeRuOsCoRhIrNiPdPt

Principle Location

Blood, liverMuscleGeneral

LiverMuscleLiver

-Liver, kidney

Liver,muscle,kidney Pediatric Nuclear Medicine 1974

Principle ExcretionFecesUrineUrineUrineUrineUrine

-Urine

Urine & Feces

Useful Positron Useful Positron IsotopesIsotopesC-11C-11

N-13N-13

O-15O-15

F-18F-18

Ga-Ga-6868

Rb-Rb-8181

Properties of a Radioactive Element That Determine

Tissue Localization and Excretion

Determinants of Localization of Radioactive Drugs

Determinants of Renal Excretion

Biodistribution of RadiopharmaceuticalsBiodistribution of Radiopharmaceuticals

Determinants of Localization of Radioactive Determinants of Localization of Radioactive DrugsDrugs

A. Organ characteristicsA. Organ characteristics

B. Drug characteristicsB. Drug characteristics

Biodistribution of RadiopharmaceuticalsBiodistribution of Radiopharmaceuticals

Biodistribution of RadiopharmaceuticalsBiodistribution of Radiopharmaceuticals

Determinants of Localization of Radioactive Determinants of Localization of Radioactive DrugsDrugs

A. Organ characteristicsA. 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

Determinants of Localization of Radioactive Drugs

B. Drug characteristicsB. Drug characteristics

Molecular size and shape

Degree and strength of binding to plasma

proteins

Lipid solubility

Specific drug receptor and transport mechanisms

Biodistribution of RadiopharmaceuticalsBiodistribution of Radiopharmaceuticals

Chemical Structures Chemical Structures Influencing Lipid Influencing Lipid

SolubilitySolubilityDecrease 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 LocalizationMechanisms of Localization Active Transport

Phagocytosis

Cell Sequestration

Capillary Blockade

Simple or Exchange Diffusion

Compartmental Localization

Metabolic Substitution

Pediatric Nuclear Medicine 1974Pediatric Nuclear Medicine 1974

Active Transport

Thyroid scanning with iodide or pertechnetate

Renal scanning with Iodohippurate

Liver scanning with HIDA

Pancreatic scanning with Selenomethionine

Pediatric Nuclear Medicine 1974Pediatric Nuclear Medicine 1974

Mechanisms of LocalizationMechanisms of Localization

Active Transport - Thyroid Active Transport - Thyroid scanning with iodide or scanning with iodide or pertechnetatepertechnetate 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 Active Transport - Liver scanning with HIDAscanning with HIDA

Mechanisms of LocalizationMechanisms 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 - ColloidsPhagocytosis - Colloids

RES

MAA

True Colloids Noncolloidal Suspensions

0.01 0.1 1 4 7 10 100Microns

Sulfur Colloid

Capillary Blockade

Phagocytosis - Liver scanning Phagocytosis - Liver scanning with colloidswith colloids

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 LocalizationMechanisms of Localization

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

Simple or Exchange Diffusion

Bone scanning with F-18 or Tc-99m phosphonates

Brain scanning with Tc-99m pertechnetate or DTPA

Mechanisms of LocalizationMechanisms of Localization

Bone Agents StructureBone Agents Structure

PyrophosphPyrophosphateate

P

OH

O

O OHP

OH

O

OH P

OH

O

OHP

OH

O

OH

H

H

MDPMDP

P

OH

O

OHP

OH

O

OH

H

OH

HDPHDP

Types of Bone ScansTypes of Bone Scans

Whole Body Limited Three-phaseWhole Body Limited Three-phase

Brain scanning with Tc-99m Brain scanning with Tc-99m pertechnetate or DTPApertechnetate or DTPA

Normal

Brain scanning with Tc-99m Brain scanning with Tc-99m pertechnetate or DTPApertechnetate or DTPA

Brain Death

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 LocalizationMechanisms of Localization

CSF Leak

Posterior Nasal

Pharynx

Cerebrospinal fluid space with In-111 DTPA

Cerebrospinal fluid space with In-111 DTPA

Metabolic SubstitutionF-18 Fluorodeoxyglucose (FDG)F-18 Fluorodeoxyglucose (FDG)Imaging for Cancer, Brain, Heart

Mechanisms of LocalizationMechanisms of Localization

Molecular Molecular Formula Formula CC66HH1111

1818FOFO44

Molecular Weight Molecular Weight 166.15 daltons166.15 daltons

Half life 110 minHalf life 110 min D-glucose CD-glucose C66HH1212OO66

M.W.= 180.16 dalM.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

Properties of a Radioactive Element That Determine

Tissue Localization and Excretion

Determinants of Localization of Radioactive Drugs

Determinants of Renal Excretion

Biodistribution of RadiopharmaceuticalsBiodistribution 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 RadiopharmaceuticalsBiodistribution of Radiopharmaceuticals

AcknowledgmentAcknowledgment

Mallinckrodt Nuclear Medicine Teaching Files

http://gamma.wustl.edu/home.html