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

Introduction: Sepantronium 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 [C-11]YM155 to non-invasively evaluate its tissue and tumor distribution in mice bearing human prostate tumor xenografts. Methods: Methods utilizing [C-11]acetyl chloride and [C-11]methyl triflate, both accessible with automated radiosynthesis boxes, were evaluated. The O-methylation of ethanolamine-alkolate with [C-11]methyl triflate proved to be the key development toward a rapid and efficient process. The whole-body distribution of [C-11] YM155 in PC-3 xenografted mice was examined using a planar positron imaging system (PPIS). Results: Sufficient quantities of radiopharmaceutical grade [C-11]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/mu mol (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 [C-11]YM155, at 40 min after injection, were 26.5 (+/-2.9) and 25.6 (+/-3.6), respectively. Conclusion: A rapid method for producing a radiopharmaceutical grade [C-11]YM155 was developed. An in vivo distribution study using PPIS showed high uptake of [C-11]YM155 in tumor tissue. Our methodology may facilitate the evaluation and prediction of response to YM155, when given as an anti-cancer agent. (C) 2013 Elsevier Inc. All rights reserved.