A novel compact MSAP reagent for one-step dual-modality probe construction via CBT/1,2-aminothiol click reaction

Abstract

Dual-modality nuclear/optical imaging offers complementary advantages for diagnosis and surgical guidance. We herein report a compact multifunctional single-attachment-point (MSAP) agent featuring a cyanine dye functionalized with a DOTA chelator and a 2-cyanobenzothiazole (CBT) moiety for regioselective conjugation via CBT/1,2-aminothiol click chemistry. Using prostate-specific membrane antigen (PSMA) as a model, we prepared a PSMA-targeted dual-modality probe (7) that exhibited excellent binding affinity (IC₅₀ = 1.35 ± 0.21 nM) without fluorescence quenching after metal chelation. Radiolabeling of 7 was achieved with a radiochemical yield >99%, and [¹¹¹In]In-7 exhibited good stability under physiological conditions. This study highlights the potential of this MSAP strategy to generate dual-modality imaging probes for preoperative diagnosis, to help surgeons to better visualize malignant lesions and delineate tumor margins during resections.