[Menu] [Previous] [Next] TUTORIAL: Radioisotope Production PET Tracers: Structure and Function Use the "Menu" button to jump to the Let's Play PET Main Menu or click on the Next (right arrowhead) and Previous (left arrowhead) buttons to proceed sequentially through the topics and tutorials. Or, you can return to the Department of Molecular and Medical Pharmacology's Home Page. Contents: Topics: PET Tracers Select a tracer from one of the following isotope groups: Oxygen Carbon Dioxide Oxygen Water Nitrogen Ammonia Carbon Acetate Carfentanil Cocaine Deprenyl Leucine Methionine N-Methylspiperone Raclopride Fluorine Haloperidol Fluorine Ion Fluorodeoxyglucose (FDG) Fluorodopa Fluoroethylspiperone Fluorouracil Rubidium 82-Rubidium I. Oxygen Oxygen-15 has a half-life of 2.1 minutes. Carbon Dioxide Radiolabeled water and carbon dioxide have both been used to study local cerebral blood flow. Oxygen [15O]-labeled water and oxygen are being evaluated for the quantification of myocardial oxygen consumption and oxygen extraction fraction. [15O]-labeled oxygen can also be used to measure tumor necrosis. Water 15O-labeled water and oxygen are being evaluated for the quantification of myocardial oxygen consumption and oxygen extraction fraction. 15O-water is also used by many PET centers as a tracer for myocardial blood perfusion (in contrast to 13N-ammonia). Use of [15O]water has the advantage of a nearly 100% extraction fraction in myocardium. The extraction is unaffected by metabolism, which conceivably could modify the extraction fractions of other tracers such as [82Rb] or [13N]ammonia; a disadvantage is the high [15O] activity concentrations in the vascular compartment of myocardium, the cardiac chambers, and the lungs. Accurate measurements of the tracer concentrations in myocardial tissue are therefore difficult. II. Nitrogen Nitrogen-13 has a half-life of 10.0 minutes. Ammonia Click on image above to view full-size image. [13N]-labeled ammonia can be used to measure blood flow. This tracer moves from the vascular space to tissue by both active transport (sodium-potassium pump) as well as by passive diffusion. Once inside cells, this tracer is primarily metabolized by the glutamic acid-glutamine pathway. [13N]-ammonia has been found to be an excellent measure of regional myocardial perfusion in both normal and diseased states. An added advantage of [13N]ammonia is the relatively short physical half-life, which allows for repeat studies. Clearance of [13N]ammonia from blood is rapid, with high tissue retention fractions, resulting in high-contrast cross-sectional images of the myocardium. [13N]ammonia studies are often combined with [18F]FDG to compare myocardial blood flow with glucose metabolism in an effort to detect "mismatch", an index of viable but compromised tissue. III. Carbon Carbon-11 has a half-life of 20.4 minutes. Acetate Click on image above to view full-size image. 11C-labeled acetate is used for measuring oxidative metabolism. The primary metabolic fuel for the myocardium are fatty acids, and therefore this tracer is very useful in assessing the metabolic status of the heart. Carfentanil Click on image above to view full-size image. Carfentanil is a mu-opiate receptor agonist that is approximately 8000 times more potent than morphine. [11C]-labeled carfentanil is use with PET to study opiate receptors in the brain (Dannals, et al., 1985, 1993). Cocaine Click on image above to view full-size image. PET can be utilized for the identification and characterization of drug binding sites in the brain. [11C]-labeled cocaine has been utilized in human and monkey brain to study the distribution and pharmokinetics of this agent. For example, it was demonstrated that cocaine is rapidly taken up and cleared from the striatum, and the time course of this parallels the temporal pattern of the "high" experienced with cocaine. PET has also been used to study the biochemical effects of cocaine. It has been demonstrated that while acute doses of cocaine have little, if any, effect on dopamine D2 receptor availability (measured with [11C]N-methylspiroperidol), chronic cocaine results in a down regulation of D2 receptors. Dopamine metabolism is also reduced in chronic cocaine abusers (measured with 6-[18F]fluoro-L-DOPA). (See Fowler, et al. for review). Deprenyl Click on image above to view full-size image. The distribution of monoamine oxidase (MAO) type B, the isoenzyme that catabolizes dopamine, has been monitored in the human brain by PET following injection of radioactive [11C]-deprenyl (Fowler, et al., 1987). Deprenyl is a potent MAO B inhibitor and has been shown to be effective in the treatment of early Parkinson's disease. Leucine Click on image above to view full-size image. [11C]-labeled methionine and leucine can be used to evaluate amino acid uptake and protein synthesis, providing an indicator of tumor viability. Methionine Click on image above to view full-size image. [11C]-labeled methionine and leucine can be used to evaluate amino acid uptake and protein synthesis, providing an indicator of tumor viability. N-Methylspiperone Click on image above to view full-size image. N-methylspiperone (N-methylspiroperidol) binds to dopaminergic D2 receptors. [11C]-labeled N-methylspiperone has been used to study the neurochemical effects of various substances on dopaminergic function. Raclopride Click on image above to view full-size image. [11C]-labeled raclopride is used in PET to study the function of dopaminergic synapses. Raclopride binds to dopamine D2 receptors and is a selective, reversible inhibitor of dopaminergic D2 receptor function (Farde, et al., 1986). IV. Fluorine Fluorine-18 has a half-life of 109 minutes. Haloperidol Click on image above to view full-size image. PET has been used to study the binding sites of haloperidol, a widely used antipsychotic and anxiety reducing drug. Haloperidol is a potent antagonist of the neurotransmitter dopamine, and acts on dopamine D2 receptors. Recent evidence suggests that haloperidol may also act on other types of dopamine receptors, since [18F]-haloperidol binding is seen in the cerebellum, a structure devoid of D2 receptors (Fowler, et al., 1990). Fluorine Ion Radiolabeled fluorine ion [18F-] was once a standard agent for clinical bone scanning. The pattern of skeletal uptake of [18F-] is similar to that of Technetium-99m-diphosphonate (conventional gamma camera tracer); normal bone structures demonstrate uniform uptake of [18F-]. Both [18F]- and [99mTc] are quite sensitive indicators of skeletal pathology but are limited in terms of pathological specificity (i.e., benign and malignant processes both result in stimulated osteoblastic activity and increased uptake). However, because [18F-] has a better bone-to-soft-tissue uptake ratio compared to [99mTc] diphosphonate, a whole-body PET bone scan may be both more anatomically accurate and more numerically precise than a comparable gamma camera study. Fluorodeoxyglucose Click on image above to view full-size image. [18F]-labeled 2-deoxyglucose (FDG) is used in neurology, cardiology and oncology to study glucose metabolism. In cardiology, [18F]-labeled FDG can be used to measure regional myocardial glucose metabolism. Although glucose is not the primary metabolic fuel of the myocardium, glucose utilization has been extensively studied as a metabolic marker in both diseased and normal myocardium. Because [18F]-labeled FDG measures glucose metabolism it is also useful for tumor localization and quantitation. FDG is potentially useful in differentiating benign from malignant forms of stimulated osteoblastic activity because of the high metabolic activity of many types of aggressive tumors. Fluorodopa Click on image above to view full-size image. 18F-labeled PET tracers are used in neurology to study metabolism, neurotransmission, and cell processes. L-[18F]DOPA can be used to examine the presynaptic distribution of stored neurotransmitter. L-DOPA is the precursor for the neurotransmitter dopamine and radiolabeled L-DOPA is taken up by dopaminergic terminals and becomes incorporated into the neurotransmitter. L-[18F]DOPA has been used clinically in the study of Parkinson's disease. Fluoroethylspiperone Click on image above to view full-size image. 18F-labeled PET tracers are used in neurology to study metabolism, neurotransmission, and cell processes. [18F]-labeled fluoroethylspiperone is a radioligand used to probe dopamine D2 recepors. [18F]-FESP binds to D2 receptors with high affinity; up to 10x higher than raclopride, for example. PET studies of dopaminergic function have been used to monitor hormonal effects (Wong, et al., 1988), aging (Iyo, et al., 1989), and neuropathological conditions such as Parkinson's disease and Schizophrenia. Fluorouracil Click on image above to view full-size image. [18F]-labeled fluorouracil has been used to measure the delivery of chemotherapeutic agents in the treatment of cancer (reviewed in Fowler, et al., 1990). V. Rubidium Rubidium-82 has a half-life of 1.25 minutes. 82-Rubidium 82Rb is used for myocardial perfusion studies, where its short half-life (76 sec) allows for rapid rest/stress paired studies to be performed. One of the distinct advantages of this tracer is that it can be produced without a cyclotron from a column generator. It has the limitation, however, of poor resolution images due to the relatively long positron range of this positron emitter. 82Rb has also been used to identify blood-brain-barrier deficits. The short half-life of 82Rb requires high-efficiency tomographs in order to obtain statistically adequate images, but offers in exchange the advantage of serial measurements in the same patient. Hence, the study of short-term effects of physiologic alterations or of drugs, for example, is possible. Return to Top of Tutorial [Menu] [Previous] [Next]
Radiolabeled water and carbon dioxide have both been used to study local cerebral blood flow.
[15O]-labeled water and oxygen are being evaluated for the quantification of myocardial oxygen consumption and oxygen extraction fraction. [15O]-labeled oxygen can also be used to measure tumor necrosis.
15O-labeled water and oxygen are being evaluated for the quantification of myocardial oxygen consumption and oxygen extraction fraction. 15O-water is also used by many PET centers as a tracer for myocardial blood perfusion (in contrast to 13N-ammonia). Use of [15O]water has the advantage of a nearly 100% extraction fraction in myocardium. The extraction is unaffected by metabolism, which conceivably could modify the extraction fractions of other tracers such as [82Rb] or [13N]ammonia; a disadvantage is the high [15O] activity concentrations in the vascular compartment of myocardium, the cardiac chambers, and the lungs. Accurate measurements of the tracer concentrations in myocardial tissue are therefore difficult.
[13N]-labeled ammonia can be used to measure blood flow. This tracer moves from the vascular space to tissue by both active transport (sodium-potassium pump) as well as by passive diffusion. Once inside cells, this tracer is primarily metabolized by the glutamic acid-glutamine pathway. [13N]-ammonia has been found to be an excellent measure of regional myocardial perfusion in both normal and diseased states. An added advantage of [13N]ammonia is the relatively short physical half-life, which allows for repeat studies. Clearance of [13N]ammonia from blood is rapid, with high tissue retention fractions, resulting in high-contrast cross-sectional images of the myocardium. [13N]ammonia studies are often combined with [18F]FDG to compare myocardial blood flow with glucose metabolism in an effort to detect "mismatch", an index of viable but compromised tissue.
11C-labeled acetate is used for measuring oxidative metabolism. The primary metabolic fuel for the myocardium are fatty acids, and therefore this tracer is very useful in assessing the metabolic status of the heart.
PET can be utilized for the identification and characterization of drug binding sites in the brain. [11C]-labeled cocaine has been utilized in human and monkey brain to study the distribution and pharmokinetics of this agent. For example, it was demonstrated that cocaine is rapidly taken up and cleared from the striatum, and the time course of this parallels the temporal pattern of the "high" experienced with cocaine. PET has also been used to study the biochemical effects of cocaine. It has been demonstrated that while acute doses of cocaine have little, if any, effect on dopamine D2 receptor availability (measured with [11C]N-methylspiroperidol), chronic cocaine results in a down regulation of D2 receptors. Dopamine metabolism is also reduced in chronic cocaine abusers (measured with 6-[18F]fluoro-L-DOPA). (See Fowler, et al. for review).
The distribution of monoamine oxidase (MAO) type B, the isoenzyme that catabolizes dopamine, has been monitored in the human brain by PET following injection of radioactive [11C]-deprenyl (Fowler, et al., 1987). Deprenyl is a potent MAO B inhibitor and has been shown to be effective in the treatment of early Parkinson's disease.
[11C]-labeled methionine and leucine can be used to evaluate amino acid uptake and protein synthesis, providing an indicator of tumor viability.
N-methylspiperone (N-methylspiroperidol) binds to dopaminergic D2 receptors. [11C]-labeled N-methylspiperone has been used to study the neurochemical effects of various substances on dopaminergic function.
PET has been used to study the binding sites of haloperidol, a widely used antipsychotic and anxiety reducing drug. Haloperidol is a potent antagonist of the neurotransmitter dopamine, and acts on dopamine D2 receptors. Recent evidence suggests that haloperidol may also act on other types of dopamine receptors, since [18F]-haloperidol binding is seen in the cerebellum, a structure devoid of D2 receptors (Fowler, et al., 1990).
Radiolabeled fluorine ion [18F-] was once a standard agent for clinical bone scanning. The pattern of skeletal uptake of [18F-] is similar to that of Technetium-99m-diphosphonate (conventional gamma camera tracer); normal bone structures demonstrate uniform uptake of [18F-]. Both [18F]- and [99mTc] are quite sensitive indicators of skeletal pathology but are limited in terms of pathological specificity (i.e., benign and malignant processes both result in stimulated osteoblastic activity and increased uptake). However, because [18F-] has a better bone-to-soft-tissue uptake ratio compared to [99mTc] diphosphonate, a whole-body PET bone scan may be both more anatomically accurate and more numerically precise than a comparable gamma camera study.
[18F]-labeled 2-deoxyglucose (FDG) is used in neurology, cardiology and oncology to study glucose metabolism. In cardiology, [18F]-labeled FDG can be used to measure regional myocardial glucose metabolism. Although glucose is not the primary metabolic fuel of the myocardium, glucose utilization has been extensively studied as a metabolic marker in both diseased and normal myocardium. Because [18F]-labeled FDG measures glucose metabolism it is also useful for tumor localization and quantitation. FDG is potentially useful in differentiating benign from malignant forms of stimulated osteoblastic activity because of the high metabolic activity of many types of aggressive tumors.
18F-labeled PET tracers are used in neurology to study metabolism, neurotransmission, and cell processes. L-[18F]DOPA can be used to examine the presynaptic distribution of stored neurotransmitter. L-DOPA is the precursor for the neurotransmitter dopamine and radiolabeled L-DOPA is taken up by dopaminergic terminals and becomes incorporated into the neurotransmitter. L-[18F]DOPA has been used clinically in the study of Parkinson's disease.
18F-labeled PET tracers are used in neurology to study metabolism, neurotransmission, and cell processes. [18F]-labeled fluoroethylspiperone is a radioligand used to probe dopamine D2 recepors. [18F]-FESP binds to D2 receptors with high affinity; up to 10x higher than raclopride, for example. PET studies of dopaminergic function have been used to monitor hormonal effects (Wong, et al., 1988), aging (Iyo, et al., 1989), and neuropathological conditions such as Parkinson's disease and Schizophrenia.
[18F]-labeled fluorouracil has been used to measure the delivery of chemotherapeutic agents in the treatment of cancer (reviewed in Fowler, et al., 1990).
82Rb is used for myocardial perfusion studies, where its short half-life (76 sec) allows for rapid rest/stress paired studies to be performed. One of the distinct advantages of this tracer is that it can be produced without a cyclotron from a column generator. It has the limitation, however, of poor resolution images due to the relatively long positron range of this positron emitter. 82Rb has also been used to identify blood-brain-barrier deficits. The short half-life of 82Rb requires high-efficiency tomographs in order to obtain statistically adequate images, but offers in exchange the advantage of serial measurements in the same patient. Hence, the study of short-term effects of physiologic alterations or of drugs, for example, is possible.
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