RT Journal Article SR Electronic T1 Quantification of peripheral benzodiazepine receptors using a new aryloxyanilide based ligand [11C]PBR28 in monkey and human JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 242P OP 242P VO 48 IS supplement 2 A1 Masao Imaizumi A1 Emmanuelle Briard A1 Sami Zoghbi A1 Jinsoo Hong A1 John Musachio A1 Jonathan Gourley A1 Robert Gladding A1 Fumihiko Yasuno A1 Tetsuya Suhara A1 Victor Pike A1 Robert Innis A1 Masahiro Fujita YR 2007 UL http://jnm.snmjournals.org/content/48/supplement_2/242P.4.abstract AB 1129 Objectives: N-acetyl-N-(2-[11C]methoxybenzyl)-2-phenoxy-5-pyridinamine ([11C]PBR28) is a potential PET ligand with highly selective and specific binding to peripheral benzodiazepine receptors (PBR), a marker of neuroinflammation. Our aim was to evaluate the kinetics of [11C]PBR28. Methods: We performed brain PET imaging of [11C]PBR28 in two rhesus monkeys (Baseline: N=6, Blocking: N=1) and nine human subjects (Baseline: N=9), measured the concentration of the parent radiotracer and radiometabolites in serial arterial plasma samples, and calculated regional distribution volume (V) with one- (1C) and two-compartment (2C) models. To determine necessary length to measure V accurately, kinetic analysis was performed by analyzing short portions of the acquired data ranging from full-length to 40 min. Results: [11C]PBR28 showed high brain uptake of 200-300% SUV in baseline scans of both species. Images showed no receptor free region that could be used for reference tissue analysis; thus, quantitation of receptor density required the measurement of parent radiotracer in plasma. 1C and 2C fitted monkey data equally well and V was 130±22 mL/cm3. V of blocking scans was ~10% of V in baseline scans indicating that ~90% of total binding was specific. V of [11C]PBR28 in monkeys was stably determined with 100 min of scanning. In seven subjects, 2C showed better fitting than 1C, and V was 3.7±0.4 mL/cm3. The smaller V values in humans than monkeys were expected from the postmortem data. Eighty min was minimally required scan length to accurately measure V for these subjects. Two subjects showed markedly different brain data and rapid washout, for which only 1C converged and gave lower V of 0.7±0.3 mL/cm3. Conclusions: Binding of [11C]PBR28 was successfully measured in both species within the time frame of 11C, indicating that [11C]PBR28 is a promising ligand. The difference in goodness-of-fit of 1C and 2C between these species was presumably caused by significantly different receptor densities. In monkeys, majority of total binding was a single compartment of specific binding, while in human, significant portion of total binding was nondisplaceable because of the lower receptor density. Research Support (if any): NIMH