An Evans blue-modified melanin-targeting theranostic agent for improved PET imaging and radionuclide therapy of malignant melanoma

Melanin is the characteristic product of the vast majority of melanomas which is the most lethal and invasive type of skin cancer. We synthesized a new probe that target melanin, H-3, and its variant that connected to the Evans blue, H-3-EB, were radiolabeled with [⁶⁸Ga]Ga and [¹⁷⁷Lu]Lu, respectively. Both [⁶⁸Ga]Ga-H-3 and [⁶⁸Ga]Ga-H-3-EB have favorable affinity and specificity for melanin, and good diagnostic efficacy for melanoma. [¹⁷⁷Lu]Lu-H-3-EB showed a more pronounced therapeutic effect than [¹⁷⁷Lu]Lu-H-3 in B16 tumors since its extended effective half life in vivo by its ability binding to albumin. [⁶⁸Ga]Ga-H-3-EB was well tolerated by malignant melanoma (MM) patients, and detected all primary melanoma lesions and lymph node metastases. This suggests that [¹⁷⁷Lu]Lu-H-3-EB could become a highly promising therapeutic option for patients with advanced melanoma.