First-in-human PET imaging and evaluation of melanin-targeted [¹⁸F]DMPY2 in malignant melanoma patients

<b>Aim:</b> Early diagnosis and accurate malignant melanoma (MM) staging are significant and decisive in clinical practice. [¹⁸F]DMPY2 is a promising PET tracer <i>in vivo</i> with high affinity and selectivity for melanin. The study aims to investigate the biodistribution and radiation dosimetry in healthy volunteers, and the potential clinical application of [¹⁸F]DMPY2 in MM patients. <b>Materials and Methods</b>: [¹⁸F]DMPY2 was synthesized via a one-pot reaction. The biodistribution, radiation dosimetry, and probe safety were estimated in three healthy volunteers. Thirty-one MM patients underwent [¹⁸F]DMPY2 and/or [¹⁸F]FDG PET/CT scans to explore the clinical use in early detection of melanoma metastasis. Diagnostic performance was assessed in fifty-one LN basins of twenty-seven MM patients after surgery, comparing PET uptake with pathological results. <b>Results</b>: [¹⁸F]DMPY2 was well tolerated by healthy volunteers and MM patients. The calculated effective dose of [¹⁸F]DMPY2 was 0.0122 mSv/MBq. In MM patients, we observed prominent [¹⁸F]DMPY2 tumor uptake and high tumor-to-background ratios in primary tumors. [¹⁸F]DMPY2 showed superior diagnostic performance in lymph node metastases compared to [¹⁸F]FDG, with sensitivity, specificity, accuracy, positive and negative predictive values of 66.7%, 100%, 88.9%, 100% and 85.7%, respectively, versus 50%, 42.9%, 46.7%, 50% and 42.9% for [¹⁸F]FDG. Additionally, [¹⁸F]DMPY2 PET imaging had a unique advantage in distinguishing [¹⁸F]FDG false-positive lesions. <b>Conclusion</b>: [¹⁸F]DMPY2 is a safe and well-tolerated melanin PET tracer and can be a powerful imaging tool for early detection and clinical staging of patients with MM.