Synthesis and evaluation of11C-PK 11195 forin vivo study of peripheral-type benzodiazepine receptors using position emission tomography

Abstract

The biodistribution of 3H-PK 11195, an antagonist of the peripheral-type benzodiazepine receptors, was studied in mice. High accumulations of radioactivity in the heart, lung, spleen, kidney and adrenal were observed after intravenous injection of tracer amounts of 3H-PK 11195 into the mice. The radioactivity in the heart, lung, spleen, kidney and adrenal was significantly decreased by the coadministration of carrier PK 11195, which indicated that PK 11195 specifically binds to the receptors. No radioactive metabolites were observed in the heart, lung and brain 20 min after intravenous administration of 3H-PK 11195. The accumulation of 3H-PK 11195 in the lung was not affected by pretreatment with either alpha-methyl benzylamine or imipramine, suggesting that 3H-PK 11195 specifically binds to the receptors. The ratios of radioactivity of the kidney, adrenal and spleen to blood increased as a function of time, whereas that of the lung and heart rapidly reached to a steady state. 11C-PK 11195 was synthesized by the N-methylation of desmethyl precursor yielding more than 100 mCi with high specific activity (more than 1.4 Ci/mumol). The labeling and purification procedure was completed within 23 min after the end of bombardment (EOB). The 11C-PK 11195 solution for injection seems to have a high potential for the in vivo study of the peripheral-type benzodiazepine receptors in the living human by means of positron emission tomography (PET).

The 18 kDa Translocator Protein and Atherosclerosis in Mice Lacking Apolipoprotein E

“…TSPO has been detected in heart of normal mice before, and we found comparable levels in our control animals (Hashimoto et al, 1989;Weizman et al, 1992;Fares et al, 1990;Katz et al, 1994;Dumont et al, 1999). To our knowledge the present study is the first study regarding TSPO binding density in the aorta of mice, which are quite high (even comparable to TSPO levels in adrenal of rats (Gavish and Fares, 1985;Gavish et al, 1999).…”

11C-AC-5216: A Novel PET Ligand for Peripheral Benzodiazepine Receptors in the Primate Brain

“…High radioactivity of 11 C-AC-5216 was also found in the brain, the target tissue in this study. The radioactivity was about 1.5-to 2-fold higher than that of 11 C-PK11195 in the mouse brain at the corresponding time points (32). These results revealed that 11 C-AC-5216 could pass through the BBB and enter the brain.…”

“…The highest radioactivity of 11 C-AC-5216 was found in the lungs (Table 1), and this radioactivity was higher than that of 11 C-PK11195 (32). Uptake in the lungs and heart may be related to mitochondrial contents containing PBR.…”

Optimized palladium‐based approaches to analogues of PK 11195

“…On the applications point of view, PBR ligands were described for their potential use in imagery techniques such as positron emission tomography [29,30]. Further results have actually been reported more recently [31][32][33][34][35][36][37][38][39].…”