¹⁸F-PFPN PET: A New and Attractive Imaging Modality for Patients with Malignant Melanoma

¹⁸F-FDG PET has limited diagnostic applications in malignant melanoma (MM). ¹⁸F-N-(2-(diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy) ethoxy)ethoxy)picolinamide (¹⁸F-PFPN) is a novel PET probe with high affinity and selectivity for melanin. We conducted a clinical study with 2 aims, first to investigate the biodistribution and radiation dosimetry of ¹⁸F-PFPN in healthy volunteers, and second, to examine the diagnostic utility of ¹⁸F-PFPN PET imaging in patients with MM. Methods: ¹⁸F-PFPN was synthesized through a fluoro-for-tosyl exchange reaction. Five healthy volunteers were enrolled to investigate the biodistribution, pharmacokinetics, radiation dosimetry, and safety of the tracer. Subsequently, a total of 21 patients with clinically suspected or confirmed MM underwent both ¹⁸F-PFPN PET/MRI and ¹⁸F-FDG PET/CT scans. The normalized SUV_max of selected lesions was determined for both tracers and compared in patient- and lesion-based analyses. Results: ¹⁸F-PFPN has an elevated radiochemical yield and was highly stable in vivo. In healthy volunteers, ¹⁸F-PFPN was safe and well tolerated, and its effective absorbed dose was comparable to that of ¹⁸F-FDG. In patient-based analysis, ¹⁸F-PFPN uptake was higher than ¹⁸F-FDG for both primary tumors and nodal metastases. In lesion-based analysis,¹⁸F-PFPN PET imaging could detect 365 metastases that were missed on ¹⁸F-FDG PET. Additionally, ¹⁸F-PFPN PET imaging had clinical value in distinguishing false-positive lesions on ¹⁸F-FDG PET. Conclusion: ¹⁸F-PFPN is a safe and well-tolerated melanin PET tracer. In a pilot clinical study, ¹⁸F-PFPN PET imaging outperformed traditional ¹⁸F-FDG PET in identifying both primary MM and its distant spread.