[18F]MEL050 as a melanin-targeted PET tracer: Fully automated radiosynthesis and comparison to 18F-FDG for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases

Abstract

Introduction: Melanoma is a highly malignant cutaneous tumor of melanin-producing cells. MEL050 is a synthetic benzamide-derived molecule that specifically binds to melanin with high affinity. Our aim was to implement a fully automated radiosynthesis of [¹⁸F]MEL050, using for the first time, the AllInOne™ synthesis module (Trasis), and to evaluate the potential of [¹⁸F]MEL050 for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases, and to compare it with that of [¹⁸F]FDG.

Methods: Automated radiosynthesis of [¹⁸F]MEL050, including HPLC purification and formulation, were performed on an AllInOne™ synthesis module. [¹⁸F]MEL050 was synthesized using a one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumor) or intravenous (pulmonary metastases) injection of B16-F10-luc2 cells in NMRI mice. The maximum percentage of [¹⁸F]MEL050 Injected Dose per g of lung tissue (%ID/g Max) was determined on PET images, compared to [¹⁸F]FDG and correlated to in vivo bioluminescence imaging.

Results: The automated radiosynthesis of [¹⁸F]MEL050 required an overall radiosynthesis time of 48min, with a yield of 13-18% (not-decay corrected) and radiochemical purity higher than 99%. [¹⁸F]MEL050 PET/CT images were concordant with bioluminescence imaging, showing increased radiotracer uptake in all primary subcutaneous tumors and pulmonary metastases of mice. PET quantification of radiotracers uptake in tumors and muscles demonstrated similar tumor-to-background ratio (TBR) with [¹⁸F]MEL050 and [¹⁸F]FDG in subcutaneous tumors and higher TBR with [¹⁸F]MEL050 than with [¹⁸F]FDG in pulmonary metastases.

Conclusion: We successfully implemented the radiosynthesis of [¹⁸F]MEL050 using the AllInOne™ module, including HPLC purification and formulation. In vivo PET/CT validation of [¹⁸F]MEL050 was obtained in mouse models of pigmented melanoma, where higher [¹⁸F]MEL050 uptake was observed in sub-millimetric pulmonary metastases, comparatively to [¹⁸F]FDG.

Keywords: Melanin; Melanoma; PET imaging; Radiosynthesis; Small-animal PET; [(18)F]MEL050.