7α-O-IA-DPN:特异性碘标记阿片配体的研制和评价

7α-O-IA-DPN:PREPARATION AND ASSESSMENT OF SPECIFIC IODINATED OPIOID LIGAND

目的：研制和评价新碘标阿片受体显像剂７αＯｉｏｄｏａｌｙｌｄｉｐｒｅｎｏｒｐｈｉｎｅ（７αＯＩＡＤＰＮ）。方法：选用阿片肽拮抗剂ＤＰＮ经碘代锡烷标记法成功地获得了一个原始的碘标阿片肽类似物，并对其进行理化性能、药理作用和生物学功能评价。结果：体外和体内阿片受体结合分析表明这一新的阿片配体具有非常高的亲和力（Ｋｉ＝４×１０－４μｍｏｌ／Ｌ）。注药后２０ｍｉｎ动物脑内的特异性结合占６３％，且其在脑内滞留时间较长而有利于成像。阿片抑制试验和抗痛活性研究分别反映碘标７αＯＩＡＤＰＮ可能对３种阿片受体（μ，δ，κ）都有亲和力，并保持了原有的药理特性和生物学功能。结论：碘标７αＯＩＡＤＰＮ作为新阿片受体显像剂较适于今后ＳＰＥＣＴ阿片受体研究。

Objective: To prepare and assess an original iodinated opioid receptor imaging agent, i.e. [^(125)I]7α-O-iodoallyl diprenorphine (7α-O-IA-DPN) Methods: The novel radioprobe was successfully obtained from DPN of nonselective opioid antagonist by iododestannylation and evaluated for its physicochemical, pharmacological and biological functions. Results: “In vitro” and “in vivo” opioid receptor binding studies showed very high affinity (Ki=4×10-4 μmol/L), 63% of 20minpostinjection specific binding and good imaging as a degradationresistant of this agent in mouse brain. Inhibition and analgesic activity studies indicated that the tracer was probably labeled with the affinities to μ, δ, κ three opioid receptors and kept its pharmacological characteristics and biological function, respectively. Conclusion: The study suggested 7α-O-IA-DPN as a new opioid receptor imaging agent suitable for SPECT studies of opioid receptors.