[(99m)Tc][Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection of alphavbeta3 Integrin: Synthesis, Structure-Activity and Pharmacokinetic Studies
[(99m)Tc][Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection of alphavbeta3 Integrin: Synthesis, Structure-Activity and Pharmacokinetic Studies(589 views) Bolzati C, Salvarese N, Carpanese D, Seraglia R, Melendez-alafort L, Rosato A, Capasso D, Saviano M, Del Gatto A, Comegna D, Zaccaro L
J Med Chem (ISSN: 0022-2623linking, 0022-2623print, 1520-4804electronic), 2018 Nov 8; 61(21): 9596-9610.
Institute of Condensed Matter Chemistry and Technologies for Energy ICMATE-CNR , Corso Stati Uniti, 4 , 35127 Padova , Italy.
Veneto Institute of Oncology IOV-IRCCS , Via Gattamelata, 64 , 35128 Padova , Italy.
Department of Surgery, Oncology and Gastroenterology , University of Padua , via Gattamelata, 64 , 35138 Padova , Italy.
Department of Pharmacy , University of Naples '' Federico II '', Naples , Italy.
Institute of Cristallography IC-CNR , Via Amendola 122/O , 70126 Bari , Italy.
Institute of Biostructures and Bioimaging IBB-CNR , Via Mezzocannone 16 , 80134 Napoli , Italy.
References: Not available.
[(99m)Tc][Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection of alphavbeta3 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 α(v)β(3). Herein, RGDechi and three truncated derivatives functionalized with a cysteine (1-4) were synthesized and labeled with the [(99m)Tc][Tc(N)PNP43]-synthon ([PNP43 = (CH(3))(2)P(CH(2))(2)N(C(2)H(4)OCH(3))(CH(2))(2)P(CH(3))(2)]) ((99m)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 (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 α(v)β(3) and α(v)β(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 α(v)β(3) expression by SPECT.
[(99m)Tc][Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection of alphavbeta3 Integrin: Synthesis, Structure-Activity and Pharmacokinetic Studies
[(99m)Tc][Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection of alphavbeta3 Integrin: Synthesis, Structure-Activity and Pharmacokinetic Studies