[Tc][Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection of αvβ Integrin: Synthesis, Structure-Activity and Pharmacokinetic Studies.

New integrin-selective molecules suitable for therapeutic or imaging purposes are currently of interest in development of effective personalized medical platforms. RGDechi is a bifunctional peptide selective for integrin αβ. Herein, RGDechi and three truncated derivatives functionalized with a cysteine (1-4) were synthesized and labeled with the [Tc][Tc(N)PNP43]-synthon ([PNP43 = (CH)P(CH)N(CHOCH)(CH)P(CH)]) (Tc1-4) as a basis for selective integrin recognition. The pharmacological parameters of all radiolabeled peptides were assessed along with the pharmacokinetic profiles of the most promising Tc1 and Tc2 compounds both on healthy and melanoma-bearing mice. Their metabolism and metabolite identification are also reported. Tc1-2 are able to discriminate between endogenously expressed integrins αβ and αβ and possess favorable pharmacokinetics characterized by low liver uptake and rapid elimination from nontarget tissues resulting in positive target-to-nontarget ratios. Results are encouraging; the presented construct can be considered the starting point for the development of agents for the selective detection of αβ expression by SPECT.