Avidin/Biotin Bioinspired Platform for Dual In Vivo ¹⁸F-PET/NIRF Molecular Imaging

Abstract

The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of innovative multimodal PET/NIRF probes a very exciting prospect. Herein, the bioinspired design of novel platform exploiting the strength and specificity of interactions between radioactive and fluorescent biotin derivatives and an avidin core is reported. The combination of an original [F]fluoropyridinylated-biotin derivative and commercially available fluorescent biotin derivatives (Atto-425 and Atto-680) is investigated. The in vivo distribution of such a customized platform is also reported, for the first time, in healthy rodent using PET and ex vivo fluorescence imaging.

PET/Fluorescence Imaging: An Overview of the Chemical Strategies to Build Dual Imaging Tools

“…The resulting imaging tool has been evaluated in vivo and showed a consistent colocalization of radioactivity from PET images and fluorescence from ex vivo imaging. 219 According to simultaneous approach as well, a first example using iodine-124 was reported in the literature in 2017. 226 The dual imaging dye has been prepared via a three-component reaction associating iodine-124, a propargylated fluorescein derivative, and 4-azidomethyl-Nsuccinimidyl benzoate.…”

Fluorine‐18 Radiolabelling and Photophysical Characteristics of Multimodal PET–Fluorescence Molecular Probes

“…A unique approach to designing PET–fluorescence agents was experimented by Damont et al. whom first sought to conjugate water‐soluble biotin (vitamin B7) to two differing fluorescent dyes, Atto‐425 ( 39 ) and Atto‐680 ( 40 ) as shown in Figure 19 [50] . A third biotin precursor ( 41 ) was also developed which was radiofluorinated via a traditional nucleophilic aromatic substitution for a nitro leaving group in anhydrous conditions, affording the 2‐[ 18 F]fluoropyridine labelled derivative ( 42 ) in 44±9 % RCY and 153±45 GBq μmol −1 molar activity.…”

“…A 2‐nitropyridine analogue of biotin ( 41 ) was radiofluorinated to form a 2‐[ 18 F]fluoropyridine biotinylated analogue ( 42 ). The PET modality ( 42 ) and fluorescence modality ( 39 or 40 ) were then combined via biotin‐avidin binding to develop a novel PET–fluorescence agent [50] …”

“…Au nique approach to designing PET-fluorescence agents was experimented by Damont et al whom first soughtt oc onjugate water-soluble biotin (vitamin B7) to two differing fluorescent dyes, Atto-425 (39)a nd Atto-680 (40)a ss hown in Figure 19. [50] At hird biotin precursor (41)w as also developed which was radiofluorinated via at raditional nucleophilic aromatic substitution for an itro leaving group in anhydrous conditions, affording the 2-[ 18 F]fluoropyridine labelled derivative (42)i n4 4AE 9% RCY and 153 AE 45 GBq mmol À1 molara ctivity.E ach of the three biotin groups weret hen bound to avidin, at etrameric protein capable of binding to four units of biotin with high affinity,i no rdert oc reate the scaffold for aP ET-optical tracer to which af ourth biotin unit could be bound as a targeting vector.N eithert he photophysical properties nor the molar activity of the final biotin-bound avidin complexw ere determined, though the approach demonstrated an ovel means by whicha dditional imaging modalities could be appended. Figure 16.…”

“…The PET modality (42)and fluorescence modality (39 or 40)w ere then combined via biotin-avidin binding to develop anovel PET-fluorescence agent. [50] . (44).…”