Radiosynthesis and in vivo evaluation of the pseudopeptide delta-opioid antagonist [I-125]-ITIPP(psi)

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(delt a) = 1280) has been synthesized and evaluated as a potential lung tumour im aging agent. [I-125]ITIPP(psi) was obtained, via electrophilic iodination, in 46% yield (>44,000 MBq/mu mol) from the parent TIPP(psi). The biodistrib ution of [I-125]ITIPP(psi) in nu/nu mice bearing SCLC-SW210.5 xenographs re vealed 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 sho wed significant reduction of uptake of the tracer in the brain, liver, inte stine and tumor indicating that the iodinated tetrapeptide binds to delta o pioid receptors in vivo. (C) 2001 Elsevier Science Inc. All rights reserved .