Atherosclerosis is a chronic progressive disease involving inflammatory events, such as the overexpression of adhesion molecules including the endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1). VCAM-1 is rapidly overexpressed in the first stages of atherosclerosis, thus representing a promising target for early atheroma detection. Two novel Positron Emission Tomography (PET) radiopharmaceuticals (MacroP and NAMP), based on the VCAM-1-binding peptide having sequence VHPKQHRGGSKGC, were synthesized and characterized. MacroP is derived from the direct conjugation of a DOTA derivative with the peptide, while NAMP is a biotin derivative conceived to be employed in a three-step pretargeting system, involving the use of a double-chelating derivative of DOTA. The identity of the newly synthesized radiopharmaceuticals was confirmed by mass spectrometry and, after radiolabeling with 68Ga, both showed high radiochemical purity; in vitro tests on human umbilical vein endothelial cells evidenced their VCAM-1 binding ability, with higher radioactive uptake in the case of NAMP. Moreover, NAMP might also be employed in a theranostic approach in association with functionalized biotinylated nanoparticles.

Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting

Baldassari, Sara;Ailuno, Giorgia;Zuccari, Guendalina;Drava, Giuliana;Petretto, Andrea;Cossu, Vanessa;Marini, Cecilia;Alfei, Silvana;Florio, Tullio;Sambuceti, Gianmario;Caviglioli, Gabriele
2021-01-01

Abstract

Atherosclerosis is a chronic progressive disease involving inflammatory events, such as the overexpression of adhesion molecules including the endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1). VCAM-1 is rapidly overexpressed in the first stages of atherosclerosis, thus representing a promising target for early atheroma detection. Two novel Positron Emission Tomography (PET) radiopharmaceuticals (MacroP and NAMP), based on the VCAM-1-binding peptide having sequence VHPKQHRGGSKGC, were synthesized and characterized. MacroP is derived from the direct conjugation of a DOTA derivative with the peptide, while NAMP is a biotin derivative conceived to be employed in a three-step pretargeting system, involving the use of a double-chelating derivative of DOTA. The identity of the newly synthesized radiopharmaceuticals was confirmed by mass spectrometry and, after radiolabeling with 68Ga, both showed high radiochemical purity; in vitro tests on human umbilical vein endothelial cells evidenced their VCAM-1 binding ability, with higher radioactive uptake in the case of NAMP. Moreover, NAMP might also be employed in a theranostic approach in association with functionalized biotinylated nanoparticles.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/1050407
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