Kinetic analysis of [11C]vorozole binding in the human brain with positron emission tomography.
Using positron emission tomography, we investigated the kinetics of [11C]vorozole ([11C]VOR), a radiotracer for the enzyme aromatase that catalyzes the last step in estrogen biosynthesis. Six subjects were scanned under baseline conditions followed by retest 2 weeks later. The retest was followed by a blocking study with 2.5 mg of the aromatase inhibitor letrozole. The binding potential (BP(A)ND) was estimated from a Lassen plot using the total tissue distribution volume (VT) for baseline and blocked. for the thalamus was found to be 15 times higher than that for the cerebellum. From the letrozole studies, we found that [11C]VOR exhibits a slow binding compartment (small k4) that has a nonspecific and a blockable component. Because of the sensitivity of VT to variations in k4, a common value was used for the four highest binding regions. We also considered the tissue uptake to plasma ratio for 60 to 90 minutes as an outcome measure. Using the ratio method, the difference between the highest and lowest was 2.4 compared to 3.5 for the VT. The ratio method underestimates the high regions but is less variable and may be more suitable for patient studies. Because of its kinetics and distribution, this tracer is not a candidate for a bolus infusion or reference tissue methods.
Jean
J
Logan
Sung Won
SW
Kim
Deborah
D
Pareto
Frank
F
Telang
Gene-Jack
GJ
Wang
Joanna S
JS
Fowler
Anat
A
Biegon
D000328:Adult; D000368:Aged; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D000077289:Letrozole; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D013788:Thalamus / Q000000981:diagnostic imaging*; D014018:Tissue Distribution; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D047072:Aromatase Inhibitors; D002250:Carbon Radioisotopes; D009570:Nitriles; D014230:Triazoles; C060523:vorozole; D000077289:Letrozole