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 in vitro and in vivo on HER2-expressing tumors demonstrated
a clear superiority of the site-specific approach to improve affinity,
specificity, and biodistribution of the bioconjugates.
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