| 20056551 |
Mou T, Jing H, Yang W, Fang W, Peng C, Guo F, Zhang X, Pang Y, Ma Y: Preparation and biodistribution of [18F] FP2OP as myocardial perfusion imaging agent for positron emission tomography. Bioorg Med Chem. 2010 Feb;18(3):1312-20. Epub 2009 Dec 26.
Myocardial extractions of pyridaben, a mitochondrial complex I (MC-I) inhibitor, is well correlated with blood flow. Based on the synthesis and characterization of pyridaben analogue 2-tert-butyl-5-[2-(2-[(18) F] fluroethoxy) ethoxy] benzyloxy]-4-chloro-2H-pyri dazin-3-one ([(18) F] FP2OP), this study assessed its potential to be developed as myocardial perfusion imaging (MPI) agent. Methods: The tosylate labeling precursor 2-(2-(4-(tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl) ben zyloxy) ethoxy) ethyl ester (OTs-P2OP) and the nonradioactive 2-tert-butyl-5-[2-(2-[(19) F] fluroethoxy) ethoxy] benzyloxy]-4-chloro-2H-pyri dazin-3-one ([(19) F] FP2OP) were synthesized and characterized by IR, (1) H NMR, (13) C NMR and MS analysis. By substituting tosyl of precursor OTs-P2OP with (18) F, the radiolabeled complex [(18) F] FP2OP was prepared and further evaluated for its in vitro physicochemical properties, in vivo biodistribution, the metabolic stability in mice, ex vivo autoradiography and cardiac PET/CT imaging. Results: Starting with [(18) F] F (-) Kryptofix 2.2.2./K (2) CO (3) solution, the total reaction time for [(18) F] FP2OP was about 100 min, with final high-performance liquid chromatography purification included. Typical decay-corrected radiochemical yield stayed at 41+/-5.3%, the radiochemical purity, 98% or more. Biodistribution in mice showed that the heart uptake of [(18) F] FP2OP was 41.90+/-4.52%ID/g at 2 min post-injection time, when the ratio of heart/liver, heart/lung and heart/blood reached 6.83, 9.49 and 35.74, respectively. Lipophilic molecule was further produced by metabolized [(18) F] FP2OP in blood and urine at 30 min. Ex vivo autoradiography demonstrates that [(18) F] FP2OP may have high affinity with MC-I and that can be blocked by [(19) F] FP2OP or rotenone (a known MC-I inhibitor). Cardiac PET images were obtained in a Chinese mini-swine at 5, 15, 30 and 60 min post-injection time with high quality. Conclusion: [(18) F] FP2OP was synthesized with high radiochemical yield. The promising biological properties of [(18) F] FP2OP suggest high potential as MPI agent for positron emission tomography in the future. |
81(1,1,1,1) |