Measurement of Benzodiazepine Receptor Number and Affinity in Humans Using Tracer Kinetic Modeling, Positron Emission Tomography, and [¹¹C]Flumazenil

Abstract

Summary: Kinetic methods were used to obtain regional estimates of benzodiazepine receptor concentration Abbreviations used: BZ, benzodiazepine; CT, computed to mography; CV, coefficient of variation; PET, positron emission tomography; SA, specific activity. 656Method I. In Methods II and III , the ko./2/SA parameter was specifically constrained using the Method I value of kon and the volunteer's values Off2 and low SA (CillLmol) . Four parameters were determined simultaneously using Method II . In Method III, K/k2 was fixed to the inhibi tion value and only three parameters were estimated. Method I provided the most variable results and conver gence problems for regions with low receptor binding. Method II provided results that were less variable but very similar to the Method I results, without convergence problems . However, the K,lk2 ratios obtained by Method II ranged from 1.07 in the occipital cortex to 0.61 in the thalamus. Fixing the K,lk2 ratio in Method III provided a method that was physiologically consistent with the fixed value of f2 and resulted in parameters with considerably lower variability . The average Bmax values obtained using Method III were 100 ± 25 nM in the occipital cortex, 64 ± 18 nM in the cerebellum , and 38 ± 5.5 nM in the thal amus; the average Kd was 8.9 ± 1.0 nM (five brain re gions).

Altered 5-HT2A Receptor Binding after Recovery from Bulimia-Type Anorexia Nervosa: Relationships to Harm Avoidance and Drive for Thinness

“…18 F]altanserin binding to plasma proteins, using previously published methods (f1, free fraction) (Price et al, 1993) .…”

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

“…The total concentration of radioactivity in plasma then was corrected for the presence of radiolabeled metabolites by multiplying the plasma concentration by the fraction of unchanged drug using linear interpolation. Further details on these procedures can be found in prior publications Price et al, 1993;Sadzot et al, 1991). Briefly, the HPLC system was equipped with two opposed 12.7-cm (5-inch) NaI (T1) detectors, a strip chart recorder, and a computer interface.…”

In vivo affinity of [18F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman primates

“…While this method works well when sustained equilibrium conditions are achieved (e.g., bolus plus constant infusion studies) (Laruelle et al 1994a,b), this method might be flawed when the equilibrium is present only for a brief time point (e.g., following single bolus injection studies) (Slifstein and Laruelle 2001). Alternatively, methods have been introduced to derive B max and K D from kinetic analysis of partial occupancy experiments (Sadzot et al 1991;Price et al 1993). These methods are more rigorous, but also more complex to implement, and potentially hampered by the number of parameters to be estimated.…”