Evaluation of radioiodinated vesamicol analogs for sigma receptor imaging in tumor and radionuclide receptor therapy
Evaluation of radioiodinated vesamicol analogs for sigma receptor imaging in tumor and radionuclide receptor therapy
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DOI：
10.1111/j.1349-7006.2009.01279.x
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发表时间：
2009-11-01
期刊：
影响因子：
5.7
通讯作者：
Mori, Hirofumi
中科院分区：
文献类型：
--
作者：
Ogawa, Kazuma;Shiba, Kazuhiro;Mori, Hirofumi
据报道，σ受体在多种人类肿瘤中高度表达。在这项研究中，我们选择（+）-2-[4-（4-碘苯基）哌啶子基]环己醇[（+）-pIV]作为σ受体配体，并评估放射性碘标记的（+）-pIV用于肿瘤成像和治疗的潜力。（+）-[125/131 I]pIV在不加载体的条件下通过碘脱锡反应制得，经HPLC纯化后放化纯度大于99%。通过将（+）-[125 I]pIV静脉注射到携带人前列腺肿瘤（DU-145）的小鼠中进行生物分布实验。通过将与过量未标记σ配体混合的（+）-[125 I]pIV静脉注射到DU-145荷瘤小鼠中进行阻断研究。对于治疗研究，以7.4 MBq的剂量注射（+）-[131 I]pIV，然后测量肿瘤大小。在生物分布实验中，（+）-[125 I]pIV显示出高摄取和在肿瘤中的长停留。由于血液和肌肉的放射性水平较低，因此肿瘤与血液和肌肉的比率较高。然而，非靶组织（如肝脏和肾脏）中的放射性蓄积较高。非靶组织中的放射性随时间缓慢降低。共注射（+）-[125 I]pIV与过量的未标记σ配体导致肿瘤/血液比显著降低，表明σ受体介导的肿瘤摄取。在治疗研究中，与未治疗组相比，（+）-[131 I]pIV治疗组小鼠的肿瘤生长受到显著抑制。这些结果表明，放射性碘标记的（+）-pIV在肿瘤和放射性核素受体治疗中具有很高的σ受体成像潜力。（Cancer Sci 2009）。
It has been reported that sigma receptors are highly expressed in a variety of human tumors. In this study, we selected (+)-2-[4-(4-iodophenyl)piperidino] cyclohexanol [(+)-pIV] as a sigma receptor ligand and evaluated the potential of radioiodinated (+)-pIV for tumor imaging and therapy. (+)-[125/131I]pIV was prepared by an iododestannylation reaction under no-carrier-added conditions with radiochemical purity over 99% after HPLC purification. Biodistribution experiments were performed by the intravenous injection of (+)-[125I]pIV into mice bearing human prostate tumors (DU-145). Blocking studies were performed by intravenous injection of (+)-[125I]pIV mixed with an excess amount of unlabeled sigma ligand into DU-145 tumor-bearing mice. For therapeutic study, (+)-[131I]pIV was injected at a dose of 7.4 MBq followed by measurement of the tumor size. In biodistribution experiments, (+)-[125I]pIV showed high uptake and long residence in the tumor. High tumor to blood and muscle ratios were achieved because the radioactivity levels of blood and muscle were low. However, the accumulations of radioactivity in non-target tissues, such as liver and kidney, were high. The radioactivity in the non-target tissues slowly decreased over time. Co-injection of (+)-[125I]pIV with an excess amount of unlabeled sigma ligand resulted in a significant decrease in the tumor/blood ratio, indicating sigma receptor-mediated tumor uptake. In therapeutic study, tumor growth in mice treated with (+)-[131I]pIV was significantly inhibited compared to that of an untreated group. These results indicate that radioiodinated (+)-pIV has a high potential for sigma receptor imaging in tumor and radionuclide receptor therapy. (Cancer Sci 2009).