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摘要
Introduction: Sigma receptors are appropriate targets for tumor imaging because they are highly expressed in a variety of human tumors. Previously, we synthesized a vesamicol analog, (+)-2-[4-(4-iodophenyl) piperidino]cyclohexanol ((+)-pIV), with high affinity for sigma receptors, and prepared radioiodinated (+)-pIV. In this study, to develop a radiobromine-labeled vesamicol analog as a sigma receptor imaging agent for PET, nonradioactive and radiobromine-labeled (+)-2-[4-(4-bromophenyl)piperidinolcyclohexanol ((+)-pBrV) was prepared and evaluated in vitro and in vivo. In these initial studies, Br-77 was used because of its longer half-life. %26lt;br%26gt;Methods: (+)-[Br-77]pBrV was prepared by a bromodestannylation reaction with radiochemical purity of 98.8% after HPLC purification. The partition coefficient of (+)-[Br-77]pBrV was measured. In vitro binding characteristics of (+)-pBrV to sigma receptors were assayed. Biodistribution experiments were performed by intravenous administration of a mixed solution of (+)-[Br-77]pBrV and ( +)-[I-125]pIV into DU-145 tumor-bearing mice. %26lt;br%26gt;Results: The lipophilicity of (+)-[Br-77]pBrV was lower than that of (+)-[I-125]pIV. As a result of in vitro binding assay to sigma receptors, the affinities of (+)-pBrV to sigma receptors were competitive to those of (+)-pIV. In biodistribution experiments, (+)-[Br-77]pBrV and (+)-[I-125]pIV showed high uptake in tumor via sigma receptors. The biodistributions of both radiotracers showed similar patterns. However, the accumulation of radioactivity in liver after injection of (+)-[Br-77]pBrV was significantly lower compared to that of (+)-[I-125]pIV. %26lt;br%26gt;Conclusion: These results indicate that radiobromine-labeled pBrV possesses great potential as a sigma receptor imaging agent for PET.
- 出版日期2013-5
