Radiosynthesis and in vivo evaluation of the pseudopeptide δ-opioid antagonist [125I]-ITIPP(ψ)
Radiosynthesis and in vivo evaluation of the pseudopeptide δ-opioid antagonist [125I]-ITIPP(ψ)
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DOI：
10.1016/s0969-8051(01)00193-7
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发表时间：
2001-05-01
影响因子：
3.1
通讯作者：
Waterhouse, RN
中科院分区：
文献类型：
--
作者：
Collier, TL;Schiller, PW;Waterhouse, RN
放射性碘标记的四肽δ-阿片拮抗剂[I-125]ITIPP（psi）[H-Tyr（3 'I）-Tic psi [CH 2NH]Phe-Phe-OH]（Ki（delta）= 2.08 nM; Ki（mu）/Ki（delta）= 1280）已被合成并被评价为潜在的肺肿瘤显像剂。[I-125]ITIPP（psi）通过亲电碘化反应从母体TIPP（psi）中获得，产率为46%（> 44，000 MBq/μ mol）。[I-125]ITIPP（psi）在携带SCLC-SW 210.5异种移植物的nu/nu小鼠中的生物分布显示，放射性在已知具有δ-阿片受体的器官中具有良好的摄取和延长的保留。代谢物分析显示，[I-125]ITIPP（psi）在PI 25 min时基本未代谢，阻断研究显示脑、肝、肠和肿瘤中示踪剂摄取显著减少，表明碘化四肽与体内δ阿片受体结合。(C)2001 Elsevier Science Inc. All rights reserved.
The radioiodinated tetrapeptide delta -opioid antagonist [I-125]ITIPP(psi) [H-Tyr(3'I)-Tic psi [CH2NH]Phe-Phe-OH] (Ki(delta) = 2.08 nM; Ki(mu)/Ki(delta) = 1280) has been synthesized and evaluated as a potential lung tumour imaging agent. [I-125]ITIPP(psi) was obtained, via electrophilic iodination, in 46% yield (>44,000 MBq/mu mol) from the parent TIPP(psi). The biodistribution of [I-125]ITIPP(psi) in nu/nu mice bearing SCLC-SW210.5 xenographs revealed good uptake and prolonged retention of radioactivity in organs known to possess delta -opioid receptors. Metabolite analysis showed that [I-125]ITIPP(psi) was largely unmetabolized at 25 min PI and blocking studies showed significant reduction of uptake of the tracer in the brain, liver, intestine and tumor indicating that the iodinated tetrapeptide binds to delta opioid receptors in vivo. (C) 2001 Elsevier Science Inc. All rights reserved.