Advancing cancer therapy with heptamethine carbocyanine dye-conjugated radionuclide drug

Malignant tumors pose substantial treatment challenges due to their heterogeneity, metastatic potential, and therapeutic resistance, underscoring the urgent need for more effective treatment options. This study developed and characterized a novel radionuclide drug conjugate (RDC) employing a tumor-targeting heptamethine carbocyanine dye (DZ) for its high specificity and favorable safety profile. The RDC, DOTA-DZ-HX, was synthesized by conjugating DZ with dodecane tetraacetic acid (DOTA) through a dipeptide linker. The anti-tumor efficacy and biodistribution of [177Lu]Lu-DOTA-DZ-HX were assessed in H1975 and Hela xenograft models. [177Lu]Lu-DOTA-DZ-HX showed high stability, specific tumor accumulation, and substantial radioactivity retention at the tumor site for seven days. Biodistribution analysis revealed that the drug exhibited prolonged blood circulation with gradual clearance. Additionally, [177Lu]Lu-DOTA-DZ-HX could effectively and selectively inhibit tumor growth, as evidenced by a significant reduction in tumor volume. These findings suggest that heptamethine carbocyanine dye-directed radionuclide targeting could provide an effective treatment for cancer and potentially other malignancies, representing a significant advancement in cancer therapy.