[99mTc][Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection of αvβ3 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 alpha(v)beta(3). Herein, RGDechi and three truncated derivatives functionalized with a cysteine (1-4) were synthesized and labeled with the [Tc-99m][Tc(N)PNP43]-synthon ([PNP43 = (CH3)(2)P(CH2)(2)N-(C2H4OCH3)(CH2)(2)P(CH3)(2)]) ((99m)Tc1-4) as a basis for selective integrin recognition. The pharmacological parameters of all radiolabeled peptides were assessed along with the pharmaco-kinetic profiles of the most promising (99m)Tc1 and (99m)Tc2 compounds both on healthy and melanoma-bearing mice. Their metabolism and metabolite identification are also reported. (99m)Tc1-2 are able to discriminate between endogenously expressed integrins alpha(v)beta(3) and alpha(v)beta(5) 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 alpha(v)beta(3) expression by SPECT.