@article {Imaizumi499P, author = {Masao Imaizumi and Emmanuelle Briard and Sami Zoghbi and Jinsoo Hong and Jay Shah and John Musachio and Victor Pike and Robert Innis and Masahiro Fujita}, title = {Kinetic and metabolic evaluation of new PET ligands for peripheral benzodiazepine receptors}, volume = {47}, number = {suppl 1}, pages = {499P--499P}, year = {2006}, publisher = {Society of Nuclear Medicine}, abstract = {1829 Objectives: Peripheral benzodiazepine receptors (PBRs) are upregulated on activated microglia. The PBR ligand [11C]PK11195 has been used to detect in vivo neuroinflammatory changes but has a high percentage of nonspecific binding. We recently developed three PET ligands based on aryloxyanilides to image PBRs. Our aim was to determine kinetics and metabolism of new PET ligands in monkey and rat brain. Methods: Following studies were performed, 2 baseline (2.5-3 h) and 2 blocking studies (1.5 h) for [11C]PBR01, 5 baseline (2-3 h) and 1 blocking studies (2 h) for [11C]PBR28, and 3 baseline (2-5 h) and 1 blocking studies (2 h) for [18F]PBR06 in rhesus monkeys. Unlabeled PBR01 (1 mg/kg), PBR28 (3 mg/kg) and an aryloxyanilide DAA1106 (3 mg/kg) were used as blocking agents. Arterial input function was obtained in all experiments, and total distribution volumes (VT{\textquoteright}s) were calculated using one- (1C) and two-compartment (2C) models. The composition of radioactivity was analyzed in rat brain by HPLC 30 min after injecting radioligands. Results: All PBR ligands showed high brain uptake of 300-400 SUV\% and greater specific/nondisplaceable ratio than [11C]PK11195 (Values of VT{\textquoteright}s are shown in table). [11C]PBR01: 1C converged but the fitting was poor in all studies. In one of 2 baseline studies, 2C did not converge. [11C]PBR28: Both 1C and 2C converged, and the 2C did not provide significantly better fitting than 1C in all baseline studies. The kinetics was described well by 1C with COV values of VT{\textquoteright}≦10\%. However, in one of two animals, 120-150 min of scanning was required to obtain apparently stable values of VT{\textquoteright}. [18F]PBR06: Both 1C and 2C converged with 5 h data, and 2C provided significantly better fitting than 1C. After 200 min, VT{\textquoteright} by 2C became independent of scan length. In the pre-blocking study, 2C did not converge with poor K4 identifiability. Profiles of plasma radiochromatograms were similar in monkey and rat. Rat brain activity detected as [11C]PBR01, [11C]PBR28 and [18F]PBR06 at 30 min was 83\%, 94\% and 90\%, respectively. Conclusions: Among the three tested PET ligands, [18F]PBR06 and [11C]PBR28 are promising for future use in human. The ratio of specific to nonspecific uptake was unusually high for both tracers (50:1). Based on the current studies, a critical factor for human use will be whether the tracer has adequately fast wash out from brain (relative to the half life of the radionuclide) to obtain stable values of VT{\textquoteright}.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/47/suppl_1/499P.2}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }