期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：23
页码：12991-12999
DOI：10.1073/pnas.1922313117
出版社：The National Academy of Sciences of the United States of America
摘要：Malignant melanoma has one of the highest mortality rates of any cancer because of its aggressive nature and high metastatic potential. Clinical staging of the disease at the time of diagnosis is very important for the prognosis and outcome of melanoma treatment. In this study, we designed and synthesized the 18 F-labeled pyridine-based benzamide derivatives N -(2-(dimethylamino)ethyl)-5-[ 18 F]fluoropicolinamide ([ 18 F]DMPY2) and N -(2-(dimethylamino)ethyl)-6-[ 18 F]fluoronicotinamide ([ 18 F]DMPY3) to detect primary and metastatic melanoma at an early stage and evaluated their performance in this task. [ 18 F]DMPY2 and [ 18 F]DMPY3 were synthesized by direct radiofluorination of the bromo precursor, and radiochemical yields were ∼15–20%. Cell uptakes of [ 18 F]DMPY2 and [ 18 F]DMPY3 were >103-fold and 18-fold higher, respectively, in B16F10 (mouse melanoma) cells than in negative control cells. Biodistribution studies revealed strong tumor uptake and retention of [ 18 F]DMPY2 (24.8% injected dose per gram of tissue [ID/g] at 60 min) and [ 18 F]DMPY3 (11.7%ID/g at 60 min) in B16F10 xenografts. MicroPET imaging of both agents demonstrated strong tumoral uptake/retention and rapid washout, resulting in excellent tumor-to-background contrast in B16F10 xenografts. In particular, [ 18 F]DMPY2 clearly visualized almost all metastatic lesions in lung and lymph nodes, with excellent image quality. [ 18 F]DMPY2 demonstrated a significantly higher tumor-to-liver ratio than [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) and the previously reported benzamide tracers N -[2-(diethylamino)-ethyl]-5-[ 18 F]fluoropicolinamide ([ 18 F]P3BZA) and N -[2-(diethylamino)-ethyl]-4-[ 18 F]fluorobenzamide ([ 18 F]FBZA) in B16F10-bearing or SK-MEL-3 (human melanoma)-bearing mice. In conclusion, [ 18 F]DMPY2 might have strong potential for the diagnosis of early stage primary and metastatic melanoma using positron emission tomography (PET).
