Quantification of human opiate receptor concentration and affinity using high and low specific activity ( sup 11 C)diprenorphine and positron emission tomography

Journal Article · Fri Mar 01 04:00:00 EST 1991 · Journal of Cerebral Blood Flow and Metabolism; (USA)

DOI:https://doi.org/10.1038/jcbfm.1991.52· OSTI ID:5944443

Sadzot, B; Price, J C; Mayberg, H S; Douglass, K H; Dannals, R F; Lever, J R; Ravert, H T; Wilson, A A; Wagner, Jr, H N; Feldman, M A ^[1]

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1. Johns Hopkins Medical Institutions, Baltimore, MD (USA)

(11C)Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) (11C)diprenorphine. Two subjects were studied a third time using high SA (11C)diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of (11C)diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of (11C)diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.

• OSTI ID: 5944443
• Journal Information: Journal of Cerebral Blood Flow and Metabolism; (USA), Journal Name: Journal of Cerebral Blood Flow and Metabolism; (USA) Vol. 11:2; ISSN 0271-678X; 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
BODY
BRAIN
CARBON 11
CARBON ISOTOPES
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
EMISSION COMPUTED TOMOGRAPHY
ENDORPHINS
EVEN-ODD NUCLEI
ISOTOPES
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MAN
MEMBRANE PROTEINS
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
PROTEINS
RADIOISOTOPES
RECEPTORS
SEPARATION PROCESSES
TISSUE DISTRIBUTION
TOMOGRAPHY
VERTEBRATES