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 [11C]YM155 to non-invasively evaluate its tissue and tumor distribution in mice bearing human prostate tumor xenografts.
METHODS: Methods 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).
RESULTS: Sufficient 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 47min. The radiochemical purity was higher than 99%, and the specific activity was 29-60GBq/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 10min after) following injection. Tumor-to-blood and tumor-to-muscle uptake ratios of [11C]YM155, at 40min after injection, were 26.5 (±2.9) and 25.6 (±3.6), respectively.
CONCLUSION: A 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.
Written by:
Murakami Y, Matsuya T, Kita A, Yamanaka K, Noda A, Mitsuoka K, Nakahara T, Miyoshi S, Nishimura S. Are you the author?
Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
Reference: Nucl Med Biol. 2013 Feb;40(2):221-6.
doi: 10.1016/j.nucmedbio.2012.10.002
PubMed Abstract
PMID: 23141550
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