Multicompartmental analysis of [11C]-carfentanil binding to opiate receptors in humans measured by positron emission tomography.
[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.
Frost
J J
JJ
Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Douglass
K H
KH
Mayberg
H S
HS
Dannals
R F
RF
Links
J M
JM
Wilson
A A
AA
Ravert
H T
HT
Crozier
W C
WC
Wagner
H N
HN
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D009270:Naloxone; D009778:Occipital Lobe / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D013788:Thalamus / Q000098:blood supply / Q000378:metabolism; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011957:Receptors, Opioid; D009270:Naloxone; C017114:carfentanil; D005283:Fentanyl