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目的 研究肿瘤血管活性肠肽受体 (VPAC受体 )显像剂的生物活性和药物动力学特性。方法 在血管活性肠肽 (VIP)C 末端加上His tag,作为水合羰基锝螯合位点和金属离子螯合层析纯化标签 ,进行 [99mTc(H2 O) 3 (CO) 3 ]+ 标记。利用家兔肛门内括约肌舒张实验、免疫细胞化学染色及竞争性受体结合实验鉴定VIP类似物MY34的生理活性。标记产物注入C5 7小鼠体内 ,行药物动力学特性分析。结果 MY34可舒张家兔肛门内括约肌 ,且能与肿瘤细胞膜上VPAC受体结合。标记化合物[99mTc(H2 O) 3 (CO) 3 ] MY34极其稳定 ,产率约为 90 %。MY34或VIP2 8均能竞争性抑制锝标小肽与肿瘤细胞膜上VPAC受体结合。锝标小肽在小鼠体内代谢符合两室开放模型 (Wi =1/C2 ) ,T1/ 2α 为16 .35min ,T1/ 2 β为 10 13.5 6min。结论 MY34具有与天然VIP2 8相似的生理活性及特异的受体结合特性
Objective To investigate the bioactivity and pharmacokinetics of tumor vasoactive intestinal peptide receptor (VPAC receptor) imaging agents. Methods The tag of [99mTc (H2 O) 3 (CO) 3] + was labeled with His tag at the C terminus of vasoactive intestinal peptide (VIP) as chelating site of hydrated carbonyl technetium and chelation chromatography of metal ions. The physiological activity of the VIP analogue MY34 was identified by the anal sphincter relaxation test, immunocytochemical staining and competitive receptor binding assay. The labeled product was injected into C5 7 mice for pharmacokinetic characterization. Results MY34 can relax the anal sphincter in rabbits and bind to the VPAC receptor on the tumor cell membrane. The labeled compound [99mTc (H2O) 3 (CO) 3] MY34 is extremely stable with a yield of about 90%. Both MY34 and VIP2 8 can competitively inhibit the binding of technetium-labeled small peptides to VPAC receptors on tumor cell membrane. The metabolism of technetium-labeled peptide in mice was in accordance with the two-compartment open model (Wi = 1 / C2), T1 / 2α was 16.35min and T1 / 2β was 10 13.56min. Conclusion MY34 has the same physiological activity as natural VIP2 8 and specific receptor binding characteristics