61Cu-Labelled radiodiagnostics of melanoma with NAPamide-targeted radiopharmaceutical

Abstract

Malignant melanoma is a major public health problem with an increasing incidence and mortality in the Caucasian population due to its significant metastatic potential. The early detection of this cancer type by imaging techniques like positron emission tomography acts as an important contributor to the long-term survival. Based on literature data, the radio labelled alpha-MSH analog NAPamide molecule is an appropriate diagnostic tool for the detection of melanoma tumors. Inspired by these facts, a new radiotracer, the [⁶¹Cu]Cu-KFTG-NAPamide has been synthesized to exploit the beneficial features of the positron emitter ⁶¹Cu and the melanoma specificity of the NAPamide molecule. In this work, we report a new member of the CB-15aneN₅ ligand family (KFTG) as the chelator for ⁶¹Cu(II) complexation. On the basis of the thorough physico-chemical characterization, the rigid [Cu(KFTG)]⁺ complex exhibits fast complex formation (t_1/2 = 155 s at pH 5.0 and 25 °C) and high inertness (t_1/2 = 2.0 h in 5.0 M HCl at 50 °C) as well as moderate superoxide dismutase activity (IC₅₀ = 2.3 μM). Furthermore, the [⁶¹Cu]Cu-KFTG-NAPamide possesses outstanding features in the diagnostics of B16-F10 melanoma tumors by PET imaging: (T/M(SUVs) (in vivo): appr. 14, %ID/g: 7 ± 1 and T/M (ex vivo): 315 ± 24 at 180 min).

Keywords: Cu-61; Melanoma; NAPamide; Positron emission tomography (PET); Radiotherapy.