Synthesis and Evaluation of a Cyanine-Bridged Somatostatin Hybrid Probe for Multimodal SSTR2-Imaging In Vitro and In Vivo.

Multimodal imaging probes have attracted the interest of ongoing research, e.g. for surgical removal of tumors. Modular synthesis approaches allow for the construction of hybrid probes consisting of a radiotracer, fluorophore and targeting unit. We present the synthesis of a new asymmetric bifunctional cyanine dye, which can be used as a structural and functional linker for the construction of such hybrid probes. 68 Ga-DOTATATE, a well-characterized radiopeptide targeting the overexpressed somatostatin receptor subtype 2 (SSTR2) in neuroendocrine tumors, was labeled with our cyanine dye, thus providing additional information along with the data obtained from the radiotracer. We tested the SSTR2-targeting and imaging properties of the resulting probe 68 Ga-DOTA-ICC-TATE in vitro and in a tumor xenograft mouse model. Despite the close proximity between dye and pharmacophore, we observed a high binding affinity towards SSTR2 as well as elevated uptake in SSTR2-overexpressing tumors in the positron emission tomography (PET) scan and histological examination.