Radiosynthesis,biodistribution and imaging of [11C]YM155, a novel survivin suppressant,in a human prostate tumor-xenograft mouse model

IntroductionSepantronium bromide (YM155) is an antitumor drug in development and is a first-in-class chemical entity, which is a survivin suppressant. We developed a radiosynthesis of ¹¹C]YM155 to non-invasively evaluate its tissue and tumor distribution in mice bearing human prostate tumor xenografts.MethodsMethods utilizing ¹¹C]acetyl chloride and ¹¹C]methyl triflate, both accessible with automated radiosynthesis boxes, were evaluated. The O-methylation of ethanolamine-alkolate with ¹¹C]methyl triflate proved to be the key development toward a rapid and efficient process. The whole-body distribution of ¹¹C]YM155 in PC-3 xenografted mice was examined using a planar positron imaging system (PPIS).ResultsSufficient quantities of radiopharmaceutical grade ¹¹C]YM155 were produced for our PET imaging and distribution studies. The decay corrected (EOB) radiochemical yield was 16–22%, within a synthesis time of 47 min. The radiochemical purity was higher than 99%, and the specific activity was 29–60 GBq/μmol (EOS). High uptake levels of radioactivity (%ID/g, mean ± SE) were observed in tumor (0.0613 ± 0.0056), kidneys (0.0513 ± 0.0092), liver (0.0368 ± 0.0043) and cecum (0.0623 ± 0.0070). The highest tumor uptake was observed at an early time point (from 10 min after) following injection. Tumor-to-blood and tumor-to-muscle uptake ratios of ¹¹C]YM155, at 40 min after injection, were 26.5 (± 2.9) and 25.6 (± 3.6), respectively.ConclusionA rapid method for producing a radiopharmaceutical grade ¹¹C]YM155 was developed. An in vivo distribution study using PPIS showed high uptake of ¹¹C]YM155 in tumor tissue. Our methodology may facilitate the evaluation and prediction of response to YM155, when given as an anti-cancer agent.