Multicompartmental analysis of (/sup 11/C)-carfentanil binding to opiate receptors in humans measured by positron emission tomography

Journal Article · Thu Jun 01 04:00:00 EDT 1989 · J. Cereb. Blood Flow Metab.; (United States)

DOI:https://doi.org/10.1038/jcbfm.1989.59· OSTI ID:6074070

Frost, J J; Douglass, K H; Mayberg, H S; Dannals, R F; Links, J M; Wilson, A A; Ravert, H T; Crozier, W C; Wagner, Jr, H N

(11C)-Carfentanil is a high affinity opiate agonist that can be used to localize mu opiate receptors in humans by positron emission tomography (PET). A four-compartment model was used to obtain quantitative estimates of rate constants for receptor association and dissociation. PET studies were performed in five normal subjects in the absence and presence of 1 mg/kg naloxone. Arterial plasma concentration of (11C)-carfentanil and its labeled metabolites were determined during each PET study. The value of k3/k4 = Bmax/kD was determined for each subject in the presence and absence of naloxone. There was a significant reduction in the value of k3/k4 from 3.4 +/- 0.92 to 0.26 +/- 0.13 in the thalamus (p less than 0.01) and from 1.8 +/- 0.33 to 0.16 +/- 0.065 in the frontal cortex (p less than 0.001). Mean values of frontal cortex/occipital cortex and thalamus/occipital cortex ratios were determined for the interval 35-70 min after injection when receptor binding is high relative to nonspecific binding. The relationship between the measured region/occipital cortex values and the corresponding values of k3/k4 in the presence and absence of naloxone was: regions/occipital cortex = 0.95 + 0.74 (k3/k4) with r = 0.98 (n = 20). Simulation studies also demonstrated a linear relationship between the thalamus/occipital cortex or frontal cortex/occipital cortex ratio and k3/k4 for less than twofold increases or decreases in k3/k4. Simulation studies in which thalamic blood flow was varied demonstrated no significant effect on the region/occipital cortex ratio at 35-70 min for a twofold increase or fourfold decrease in blood flow. Therefore, the region/occipital cortex ratio can be used to quantitate changes in k3/k4 when tracer kinetic modeling is not feasible.

• Research Organization: Johns Hopkins Medical Institutions, Baltimore, MD (USA)
• OSTI ID: 6074070
• Journal Information: J. Cereb. Blood Flow Metab.; (United States), Journal Name: J. Cereb. Blood Flow Metab.; (United States) Vol. 9:3; ISSN JCBMD
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
BLOOD FLOW
BODY
BRAIN
CARBON 11
CARBON ISOTOPES
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DRUGS
EMISSION COMPUTED TOMOGRAPHY
ENDORPHINS
EVEN-ODD NUCLEI
ISOTOPES
KINETICS
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MAN
MATHEMATICAL MODELS
MEMBRANE PROTEINS
METABOLITES
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SEPARATION PROCESSES
THALAMUS
TOMOGRAPHY
VERTEBRATES