¹⁸F-5-FPN: A Specific Probe for Monitoring Photothermal Therapy Response in Malignant Melanoma

Previously, we successfully synthesized a ¹⁸F-labeled positron-emission tomography (PET) tracer, termed ¹⁸F-5-fluoro-N-(2-[diethylamino]ethyl)picolinamide (¹⁸F-5-FPN), with high specificity for melanin. In this study, we sought to investigate the value of ¹⁸F-5-FPN in assessing the response to photothermal therapy (PTT) in melanoma via comparison with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) to reveal an early response, recognize early recurrence, and distinguish the inflammatory response during the treatment. B16F10, inflammatory, and MDA-MB-231 models were subjected to ¹⁸F-FDG PET and ¹⁸F-5-FPN PET static acquisitions. We compared quantitative data to assess the specificity of different agents for different diseases. B16F10 and MDA-MB-231subcutaneous tumor models were irradiated with an 808 nm laser for PTT. Their survival was documented to observe the efficacy of and response to PTT, using ¹⁸F-5-FPN and ¹⁸F-FDG PET. ¹⁸F-5-FPN accumulated in B16F10 cell xenografts only, whereas ¹⁸F-FDG accumulated in all three models. Melanin in B16F10 cell xenografts successfully transformed the optical energy into heat. Hematoxylin and eosin (H&E) staining at 24 h revealed destruction and extensive necrosis of tumor tissue. PTT rapidly inhibited the growth of B16F10 cell xenografts and prolonged the median survival. The mean tumor uptakes of ¹⁸F-5-FPN on day 2 (7.52 ± 3.65 %ID/g) and day 6 (10.22 ± 6.00 %ID/g) were much lower than that before treatment (18.33 ± 4.98 %ID/g, p < 0.01). However, a significant difference in ¹⁸F-FDG uptakes was not found between day 1 after PTT and before treatment. Compared with ¹⁸F-FDG, ¹⁸F-5-FPN PET could estimate PTT efficacy in melanoma, monitor minimal recurrence, and distinguish melanoma from inflammation and other carcinoma types, thanks to its high affinity to melanin. ¹⁸F-5-FPN may provide a new approach for precise and accurate evaluation of response, timely management of therapeutic regimens, and sensitive follow-up.