Synthesis and comparative assessment of a labeled RGD peptide bearing two different 99mTc-tricarbonyl chelators for potential use as targeted radiopharmaceutical

dc.contributor.author	Ψιμάδας, Δημήτριος	el
dc.contributor.author	Φανή, Μελπομένη	el
dc.contributor.author	Γκούρνη, Ελένη	el
dc.contributor.author	Λούντος, Γεώργιος	el
dc.contributor.author	Ξανθόπουλος, Σταύρος	el
dc.date.accessioned	2015-05-24T11:48:32Z
dc.date.available	2015-05-24T11:48:32Z
dc.date.issued	2015-05-24
dc.identifier.uri	http://hdl.handle.net/11400/11034
dc.rights	Αναφορά Δημιουργού-Μη Εμπορική Χρήση-Όχι Παράγωγα Έργα 3.0 Ηνωμένες Πολιτείες	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/us/	*
dc.source	http://www.sciencedirect.com/science/article/pii/S0968089612001538	en
dc.subject	Radiopharmaceuticals
dc.subject	Technetium
dc.subject	Ραδιοφάρμακα
dc.subject	Τεχνήτιο
dc.title	Synthesis and comparative assessment of a labeled RGD peptide bearing two different 99mTc-tricarbonyl chelators for potential use as targeted radiopharmaceutical	en
heal.type	journalArticle
heal.classification	Medicine
heal.classification	Biomedical engineering
heal.classification	Ιατρική
heal.classification	Βιοϊατρική τεχνολογία
heal.classificationURI	http://id.loc.gov/authorities/subjects/sh00006614
heal.classificationURI	http://id.loc.gov/authorities/subjects/sh85014237
heal.classificationURI	N/A-Ιατρική
heal.classificationURI	N/A-Βιοϊατρική τεχνολογία
heal.keywordURI	http://id.loc.gov/authorities/subjects/sh85110790
heal.keywordURI	http://id.loc.gov/authorities/subjects/sh85133086
heal.contributorName	Ζήκος, Χρήστος	el
heal.contributorName	Μπουζιώτη, Πηνελόπη	el
heal.contributorName	Βαρβαρήγου, Αλεξάνδρα Δ.	el
heal.identifier.secondary	doi:10.1016/j.bmc.2012.02.051
heal.language	en
heal.access	campus
heal.recordProvider	Τ.Ε.Ι. Αθήνας. Σχολή Τεχνολογικών Εφαρμογών. Τμήμα Μηχανικών Βιοϊατρικής Τεχνολογίας Τ.Ε.	el
heal.publicationDate	2012
heal.bibliographicCitation	Psimadas, D., Fani, M., Gourni, E., Loudos, G., Xanthopoulos, S., et al. (April 2012). Synthesis and comparative assessment of a labeled RGD peptide bearing two different 99mTc-tricarbonyl chelators for potential use as targeted radiopharmaceutical. Bioorganic & Medicinal Chemistry. 20(8). pp. 2549-2557. Elsevier Ltd: 2012. Available from: http://www.sciencedirect.com/science/article/pii/S0968089612001538 [Accessed 03/03/2012]	en
heal.abstract	During the past decade radiolabeled RGD-peptides have been extensively studied to develop site-directed targeting vectors for integrins. Integrins are heterodimeric cell-surface adhesion receptors, which are upregulated in cancer cells and neovasculature during tumor angiogenesis and recognize the RGD aminoacid sequence. In the present study, we report the synthesis and development of two derivatives of the Nε-Lys derivatized cyclic Arg-Gly-Asp-d-Phe-Lys peptide, namely of cRGDfKHis and cRGDfK-CPA (CPA: 3-l-Cysteine Propionic Acid), radiolabeled via the [99mTc(H2O)3(CO)3]+ metal aquaion at a high yield even at low concentrations of 10–5 M (>87%) for cRGDfK-10–5 M (>93%) for cRGDfK-CPA. Radiolabeled peptides were characterized with regard to their stability in saline, in His/Cys solutions, as well as in plasma, serum and tissue homogenates and were found to be practically stable. Internalization and efflux assays using αvβ3-receptor-positive MDA-MB 435 breast cancer cells showed a good percentage of quick internalization (29.1 ± 9.8% for 99mTc-HiscRGDfK and 37.0 ± 0.7% for 99mTc-CPA-cRGDfK at 15 min) and no retention of radioactivity for both derivatives. Their in vivo behavior was assessed in normal mice and pathological SCID mice bearing MDA-MB 435 ανβ3 positive breast tumors. Both presented fast blood clearance and elimination via both the urinary and hepatobiliary systems, with 99mTc-His-cRGDfK remaining for a longer time than 99mTc-CPA-cRGDfK in all organs examined. Tumor uptake 30 min pi was higher for 99mTc-CPAcRGDfK (4.2 ± 1.5% ID/g) than for 99mTc-His-cRGDfK (2.8 ± 1.5% ID/g). Dynamic scintigraphic studies showed that the tumor could be visualized better between 15 and 45 min pi for both radiolabeled compounds but low delineation occurred due to high abdominal background. It was finally noticed that the accumulated activity on the tumor site was depended on the size of the experimental tumor; the smaller the size, the higher was the radioactivity concentration.	en
heal.publisher	Elsevier Ltd	en
heal.journalName	Bioorganic & Medicinal Chemistry	en
heal.journalType	peer-reviewed
heal.fullTextAvailability	true