biodistribution of radiopharmaceuticals
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
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