RESUMEN
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.
Asunto(s)
Fluorodesoxiglucosa F18 , Melanoma , Humanos , Terapia Fototérmica , Melaninas , Melanoma/diagnóstico por imagen , Melanoma/terapia , Melanoma/metabolismo , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Melanoma Cutáneo MalignoRESUMEN
INTRODUCTION: 18F-5-fluoro-N-(2-(Diethylamino)ethyl)picolinamide (18F-5-FPN) is a new positron-emission tomography (PET) radiopharmaceutical with potential for the detection of lymph node (LN) and pulmonary metastatic lesions of melanoma. We compared its performance with that of 18F-deoxyglucose (18F-FDG). METHODS: Cervical LN and lung melanoma metastasis models were established in C57BL/6 mice. Primary tumors were created by injection of melanoma cells into the pinna, and the resulting cervical LN metastases were evaluated. Lung metastases were created by intravenous injection of melanoma cells. The mice underwent 18F-FDG and 18F-5-FPN positron emission tomography (PET) imaging. A biodistribution study was conducted after imaging. Histopathologic evaluation of the tumors was also performed. RESULTS: LN metastases with a diameter<1cm were more visible on 18F-5-FPN PET imaging than 18F-FDG imaging. Quantitative analysis showed that the uptake of 18F-5-FPN was significantly higher than that of 18F-FDG, with values of 13.29±3.80% ID/g and 7.24±1.95% ID/g (n=5, P<0.05), respectively. LN-to-muscle ratios were 21.23±6.02 and 4.50±2.11 (n=5, P<0.01) for 18F-5-FPN and 18F-FDG, respectively. Biodistribution results were similar, with high uptake of 18F-5-FPN in the LN. 18F-5-FPN imaging manifested the pulmonary lesions clearly, while the 18F-FDG imaging showed no uptake in lesions <2mm. The related uptakes of 18F-5-FPN and 18F-FDG were 3.12±1.17% ID/g and 1.48±0.15% ID/g, respectively (n=5, P<0.05), with lung metastasis-to-muscle ratios of 8.16±3.12 and 1.28±0.18 (n=5, P<0.01), respectively. H&E and Prussian blue staining displayed pluri nucleated or mega nucleus cells and dark brown granules in the metastatic tissues, characteristic of melanoma. CONCLUSIONS: 18F-5-FPN targeted small metastatic lesions with a higher target-to-normal ratio of uptake than those of 18F-FDG, which suggests its ability to detect metastatic lesions earlier than 18F-FDG. Further studies with a wide range of melanoma cell lines should be needed to confirm the similar performance.