Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting
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...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/7/1025 |
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| author | Sara Pastorino Sara Baldassari Giorgia Ailuno Guendalina Zuccari Giuliana Drava Andrea Petretto Vanessa Cossu Cecilia Marini Silvana Alfei Tullio Florio Gianmario Sambuceti Gabriele Caviglioli |
| author_facet | Sara Pastorino Sara Baldassari Giorgia Ailuno Guendalina Zuccari Giuliana Drava Andrea Petretto Vanessa Cossu Cecilia Marini Silvana Alfei Tullio Florio Gianmario Sambuceti Gabriele Caviglioli |
| author_sort | Sara Pastorino |
| collection | DOAJ |
| description | 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 <sup>68</sup>Ga, 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. |
| first_indexed | 2024-03-10T09:28:25Z |
| format | Article |
| id | doaj.art-8a8a800f5fc344eebfc31a03382e71e0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T09:28:25Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8a8a800f5fc344eebfc31a03382e71e02023-11-22T04:40:52ZengMDPI AGPharmaceutics1999-49232021-07-01137102510.3390/pharmaceutics13071025Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) TargetingSara Pastorino0Sara Baldassari1Giorgia Ailuno2Guendalina Zuccari3Giuliana Drava4Andrea Petretto5Vanessa Cossu6Cecilia Marini7Silvana Alfei8Tullio Florio9Gianmario Sambuceti10Gabriele Caviglioli11Nuclear Medicine Unit, S. Andrea Hospital, via Vittorio Veneto 197, 19124 La Spezia, ItalyDepartment of Pharmacy, University of Genova, viale Cembrano 4, 16148 Genova, ItalyDepartment of Pharmacy, University of Genova, viale Cembrano 4, 16148 Genova, ItalyDepartment of Pharmacy, University of Genova, viale Cembrano 4, 16148 Genova, ItalyDepartment of Pharmacy, University of Genova, viale Cembrano 4, 16148 Genova, ItalyCore Facilities-Clinical Proteomics and Metabolomics, IRCCS Istituto Giannina Gaslini, via Gerolamo Gaslini 5, 16147 Genova, ItalyDepartment of Health Science, University of Genova—Nuclear Medicine Unit, via A. Pastore 1, 16132 Genova, ItalyDepartment of Health Science, University of Genova—Nuclear Medicine Unit, via A. Pastore 1, 16132 Genova, ItalyDepartment of Pharmacy, University of Genova, viale Cembrano 4, 16148 Genova, ItalyIRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genova, ItalyDepartment of Health Science, University of Genova—Nuclear Medicine Unit, via A. Pastore 1, 16132 Genova, ItalyDepartment of Pharmacy, University of Genova, viale Cembrano 4, 16148 Genova, ItalyAtherosclerosis 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 <sup>68</sup>Ga, 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.https://www.mdpi.com/1999-4923/13/7/1025radiopharmaceuticalsVCAM-1pretargetingimagingPETGallium-68 |
| spellingShingle | Sara Pastorino Sara Baldassari Giorgia Ailuno Guendalina Zuccari Giuliana Drava Andrea Petretto Vanessa Cossu Cecilia Marini Silvana Alfei Tullio Florio Gianmario Sambuceti Gabriele Caviglioli Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting Pharmaceutics radiopharmaceuticals VCAM-1 pretargeting imaging PET Gallium-68 |
| title | Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting |
| title_full | Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting |
| title_fullStr | Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting |
| title_full_unstemmed | Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting |
| title_short | Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting |
| title_sort | two novel pet radiopharmaceuticals for endothelial vascular cell adhesion molecule 1 vcam 1 targeting |
| topic | radiopharmaceuticals VCAM-1 pretargeting imaging PET Gallium-68 |
| url | https://www.mdpi.com/1999-4923/13/7/1025 |
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