{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:02:05Z","timestamp":1760151725886,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T00:00:00Z","timestamp":1649894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bracco Imaging SpA","award":["none"],"award-info":[{"award-number":["none"]}]},{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["AIRC, IG 2020 ID 24528"],"award-info":[{"award-number":["AIRC, IG 2020 ID 24528"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: The [99mTc][Tc(N)(PNP)] system, where PNP is a bisphosphinoamine, is an interesting platform for the development of tumor \u2018receptor-specific\u2019 agents. Here, we compared the reactivity and impact of three [Tc(N)(PNP)] frameworks on the stability, receptor targeting properties, biodistribution, and metabolism of the corresponding [99mTc][Tc(N)(PNP)]-tagged cRGDfK peptide to determine the best performing agent and to select the framework useful for the preparation of [99mTc][Tc(N)(PNP)]-housing molecular targeting agents. Methods: cRGDfK pentapeptide was conjugated to Cys and labeled with each [Tc(N)(PNP)] framework. Radioconjugates were assessed for their lipophilicity, stability, in vitro and in vivo targeting properties, and performance. Results: All compounds were equally synthetically accessible and easy to purify (RCY \u2265 95%). The main influences of the synthon on the targeting peptide were observed in in vitro cell binding and in vivo. Conclusions: The variation in the substituents on the phosphorus atoms of the PNP enables a fine tuning of the biological features of the radioconjugates. ws[99mTc][Tc(N)(PNP3OH)]\u2013 and [99mTc][Tc(N)(PNP3)]\u2013 are better performing synthons in terms of labeling efficiency and in vivo performance than the [99mTc][Tc(N)(PNP43)] framework and are therefore more suitable for further radiopharmaceutical purposes. Furthermore, the good labeling properties of the ws[99mTc][Tc(N)(PNP3OH)]\u2013 framework can be exploited to extend this technology to the labeling of temperature-sensitive biomolecules suitable for SPECT imaging.<\/jats:p>","DOI":"10.3390\/molecules27082548","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T01:03:01Z","timestamp":1650330181000},"page":"2548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Different [Tc(N)PNP]-Scaffolds on the Biological Properties of the Small cRGDfK Peptide: Synthesis, In Vitro and In Vivo Evaluations"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9351-382X","authenticated-orcid":false,"given":"Nicola","family":"Salvarese","sequence":"first","affiliation":[{"name":"Institute of Condensed Matter Chemistry and Technologies for Energy ICMATE-CNR, Corso Stati Uniti, 4, 35127 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora","family":"Carpanese","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35138 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0701-3616","authenticated-orcid":false,"given":"Laura","family":"Mel\u00e9ndez-Alafort","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35138 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0061-370X","authenticated-orcid":false,"given":"Laura","family":"De Nardo","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, University of Padova, Via Marzolo 8, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Calderan","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry of CNR, Padova Unit, Via Marzolo 1, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2393-7333","authenticated-orcid":false,"given":"Barbara","family":"Biondi","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry of CNR, Padova Unit, Via Marzolo 1, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5596-9295","authenticated-orcid":false,"given":"Paolo","family":"Ruzza","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry of CNR, Padova Unit, Via Marzolo 1, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-8386","authenticated-orcid":false,"given":"Antonio","family":"Rosato","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35138 Padova, Italy"},{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Gattamelata 64, 35138 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7919-516X","authenticated-orcid":false,"given":"Cristina","family":"Bolzati","sequence":"additional","affiliation":[{"name":"Institute of Condensed Matter Chemistry and Technologies for Energy ICMATE-CNR, Corso Stati Uniti, 4, 35127 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.2174\/092986710791859388","article-title":"99mTc-Radiolabelled Peptides for Tumour Imaging: Present and Future","volume":"17","author":"Bolzati","year":"2010","journal-title":"Curr. 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