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

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Melanoma Melanin Medicine Nuclear medicine Cancer research Pathology Chemistry Biochemistry

Yi Yang , Ming Zhou , Shuang Zhao , Tingting Long , Na Chen , Xingming Wang , Yulai Li , Xiaozhen Chen , Junchen Chen , Xinqiong Huang , Dengming Chen , Juan Su , Shuo Hu , Xiang Chen ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.7150/thno.109243 · OA: W4410306086

Aim: Early diagnosis and accurate malignant melanoma (MM) staging are significant and decisive in clinical practice. [18F]DMPY2 is a promising PET tracer in vivo 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. Materials and Methods: [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. Results: [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. Conclusion: [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.