Privat Malorie, Bellaye Pierre-Simon, Chazeau Elisa, Racoeur Cindy, Adumeau Pierre, Vivier Delphine, Bernhard Claire, Moreau Mathieu, Collin Bertrand, Bettaieb Ali, Denat Franck, Bodio Ewen, Paul Catherine, Goze Christine
ICMUB, UMR 6302 CNRS, Université Bourgogne Franche-Comté, 9 av. A. Savary, BP 47870, 21078 Dijon, France.
Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75014 Paris, France.
Bioconjug Chem. 2023 Mar 27. doi: 10.1021/acs.bioconjchem.3c00080.
Among all approaches in molecular imaging, the combination of near-infrared fluorescence imaging (NIRF) with radioisotopic imaging (PET or SPECT) allows one to benefit from the advantages of each of the imaging techniques, which are very complementary and of comparable sensitivity. To this end, the construction of monomolecular multimodal probes (MOMIP) has made it possible to combine the two imaging modalities within the same molecule, thus limiting the number of bioconjugation sites and yielding more homogeneous conjugates compared with those prepared through sequential conjugation. However, in order to optimize the bioconjugation strategy and, at the same time, the pharmacokinetic and biodistribution properties of the resulting imaging agent, a site-specific approach may be preferred. To further investigate this hypothesis, random and glycan-based site-specific bioconjugation approaches were compared thanks to a SPECT/NIRF bimodal probe based on an aza-BODIPY fluorophore. The overall experiments conducted and on HER2-expressing tumors demonstrated a clear superiority of the site-specific approach to improve affinity, specificity, and biodistribution of the bioconjugates.
在分子成像的所有方法中，近红外荧光成像（NIRF）与放射性同位素成像（PET或SPECT）相结合，使人们能够从每种成像技术的优势中获益，这两种技术具有很强的互补性且灵敏度相当。为此，单分子多模态探针（MOMIP）的构建使得在同一分子内结合两种成像方式成为可能，因此与通过顺序偶联制备的偶联物相比，限制了生物偶联位点的数量，并产生了更均匀的偶联物。然而，为了优化生物偶联策略，同时优化所得成像剂的药代动力学和生物分布特性，位点特异性方法可能更受青睐。为了进一步研究这一假设，借助基于氮杂BODIPY荧光团的SPECT/NIRF双模态探针，比较了随机和基于聚糖的位点特异性生物偶联方法。在HER2表达肿瘤上进行的整体实验表明，位点特异性方法在提高生物偶联物的亲和力、特异性和生物分布方面具有明显优势。
