Advancing cancer therapy with a 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. In this study, a novel radionuclide drug conjugate (RDC) was developed and characterized employing a tumor-targeting heptamethine carbocyanine dye (DZ) for its high specificity and favourable 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.