Clickable <em>C</em>-Glycosyl Scaffold for the Development of a Dual Fluorescent and [<sup>18</sup>F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging
Considering the individual characteristics of positron emission tomography (PET) and optical imaging (OI) in terms of sensitivity, spatial resolution, and tissue penetration, the development of dual imaging agents for bimodal PET/OI imaging is a growing field. A current major breakthrough in this fi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/12/1490 |
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| author | Julen Ariztia Kamal Jouad Valérie Jouan-Hureaux Julien Pierson Charlotte Collet Bertrand Kuhnast Katalin Selmeczi Cédric Boura Sandrine Lamandé-Langle Nadia Pellegrini Moïse |
| author_facet | Julen Ariztia Kamal Jouad Valérie Jouan-Hureaux Julien Pierson Charlotte Collet Bertrand Kuhnast Katalin Selmeczi Cédric Boura Sandrine Lamandé-Langle Nadia Pellegrini Moïse |
| author_sort | Julen Ariztia |
| collection | DOAJ |
| description | Considering the individual characteristics of positron emission tomography (PET) and optical imaging (OI) in terms of sensitivity, spatial resolution, and tissue penetration, the development of dual imaging agents for bimodal PET/OI imaging is a growing field. A current major breakthrough in this field is the design of monomolecular agent displaying both a radioisotope for PET and a fluorescent dye for OI. We took advantage of the multifunctionalities allowed by a clickable <i>C</i>-glycosyl scaffold to gather the different elements. We describe, for the first time, the synthesis of a cyanine-based dual PET/OI imaging probe based on a versatile synthetic strategy and its direct radiofluorination via [<sup>18</sup>F]F-C bond formation. The non-radioactive dual imaging probe coupled with two <i>c</i>(RGDfK) peptides was evaluated in vitro and in vivo in fluorescence imaging. The binding on α<sub>v</sub>β<sub>3</sub> integrin (IC<sub>50</sub> = 16 nM) demonstrated the efficiency of the dimeric structure and PEG linkers in maintaining the affinity. In vivo fluorescence imaging of U-87 MG engrafted nude mice showed a high tumor uptake (40- and 100-fold increase for orthotopic and ectopic brain tumors, respectively, compared to healthy brain). In vitro and in vivo evaluations and resection of the ectopic tumor demonstrated the potential of the conjugate in glioblastoma cancer diagnosis and image-guided surgery. |
| first_indexed | 2024-03-09T15:59:41Z |
| format | Article |
| id | doaj.art-c8a8c7c6731d4910a4e2cddc49c93d42 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T15:59:41Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c8a8c7c6731d4910a4e2cddc49c93d422023-11-24T17:16:04ZengMDPI AGPharmaceuticals1424-82472022-11-011512149010.3390/ph15121490Clickable <em>C</em>-Glycosyl Scaffold for the Development of a Dual Fluorescent and [<sup>18</sup>F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence ImagingJulen Ariztia0Kamal Jouad1Valérie Jouan-Hureaux2Julien Pierson3Charlotte Collet4Bertrand Kuhnast5Katalin Selmeczi6Cédric Boura7Sandrine Lamandé-Langle8Nadia Pellegrini Moïse9Université de Lorraine, CNRS, L2CM, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, L2CM, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, CRAN, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, CRAN, F-54000 Nancy, FranceNancycloTEP, Molecular Imaging Platform, CHRU-Nancy, Université de Lorraine, F-54000 Nancy, FranceLaboratoire d’Imagerie Biomédicale Multimodale Paris-Saclay, CEA, CNRS, Inserm, Université Paris-Saclay, F-91401 Orsay, FranceUniversité de Lorraine, CNRS, L2CM, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, CRAN, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, L2CM, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, L2CM, F-54000 Nancy, FranceConsidering the individual characteristics of positron emission tomography (PET) and optical imaging (OI) in terms of sensitivity, spatial resolution, and tissue penetration, the development of dual imaging agents for bimodal PET/OI imaging is a growing field. A current major breakthrough in this field is the design of monomolecular agent displaying both a radioisotope for PET and a fluorescent dye for OI. We took advantage of the multifunctionalities allowed by a clickable <i>C</i>-glycosyl scaffold to gather the different elements. We describe, for the first time, the synthesis of a cyanine-based dual PET/OI imaging probe based on a versatile synthetic strategy and its direct radiofluorination via [<sup>18</sup>F]F-C bond formation. The non-radioactive dual imaging probe coupled with two <i>c</i>(RGDfK) peptides was evaluated in vitro and in vivo in fluorescence imaging. The binding on α<sub>v</sub>β<sub>3</sub> integrin (IC<sub>50</sub> = 16 nM) demonstrated the efficiency of the dimeric structure and PEG linkers in maintaining the affinity. In vivo fluorescence imaging of U-87 MG engrafted nude mice showed a high tumor uptake (40- and 100-fold increase for orthotopic and ectopic brain tumors, respectively, compared to healthy brain). In vitro and in vivo evaluations and resection of the ectopic tumor demonstrated the potential of the conjugate in glioblastoma cancer diagnosis and image-guided surgery.https://www.mdpi.com/1424-8247/15/12/1490<i>C</i>-glycosyl compounds<i>c</i>(RGDfK)cyanine-5fluorine-18fluorescencePET |
| spellingShingle | Julen Ariztia Kamal Jouad Valérie Jouan-Hureaux Julien Pierson Charlotte Collet Bertrand Kuhnast Katalin Selmeczi Cédric Boura Sandrine Lamandé-Langle Nadia Pellegrini Moïse Clickable <em>C</em>-Glycosyl Scaffold for the Development of a Dual Fluorescent and [<sup>18</sup>F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging Pharmaceuticals <i>C</i>-glycosyl compounds <i>c</i>(RGDfK) cyanine-5 fluorine-18 fluorescence PET |
| title | Clickable <em>C</em>-Glycosyl Scaffold for the Development of a Dual Fluorescent and [<sup>18</sup>F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging |
| title_full | Clickable <em>C</em>-Glycosyl Scaffold for the Development of a Dual Fluorescent and [<sup>18</sup>F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging |
| title_fullStr | Clickable <em>C</em>-Glycosyl Scaffold for the Development of a Dual Fluorescent and [<sup>18</sup>F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging |
| title_full_unstemmed | Clickable <em>C</em>-Glycosyl Scaffold for the Development of a Dual Fluorescent and [<sup>18</sup>F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging |
| title_short | Clickable <em>C</em>-Glycosyl Scaffold for the Development of a Dual Fluorescent and [<sup>18</sup>F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging |
| title_sort | clickable em c em glycosyl scaffold for the development of a dual fluorescent and sup 18 sup f fluorinated cyanine containing probe and preliminary in vitro vivo evaluation by fluorescence imaging |
| topic | <i>C</i>-glycosyl compounds <i>c</i>(RGDfK) cyanine-5 fluorine-18 fluorescence PET |
| url | https://www.mdpi.com/1424-8247/15/12/1490 |
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