Comparative evaluation of [18F]DMPY2, [18F]P3BZA and [18F]FBZA for PET imaging of malignant melanoma in small animal models

1471 Objectives: 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 18F-labeled pyridine based benzamide derivative N-(2-(dimethylamino)ethyl)-5-[18F]fluoropicolinamide ([18F]DMPY2) and compared with conventional positron emission tomography (PET) imaging agents in early stage primary and metastatic melanoma animal models. Methods: [18F]DMPY2 was synthesized by direct radiofluorination of the bromo precursor, and radiochemical yields were ∼15-20%. B16F10 cells (5 × 104) were plated into a 24-well plate and were incubated at 37℃ for 10, 30, and 60 min with 0.74 MBq of [18F]DMPY2. B16F10 cells (1 × 106) were subcutaneously implanted into the right shoulder of nude mice. After about 10 days, mice were used for experiments when the tumor size reached approximately 100 to 150 mm3. For the SK-MEL-3 (human melanoma) subcutaneous tumor model, 3 × 106 SK-MEL-3 cells in 100 μl PBS were implanted into the right shoulder of nude mouse that were imaged after 21 days. The mircoPET images were obtained at 60 min after i.v. injection of [18F]DMPY2, N-[2-(diethylamino)-ethyl]-5-[18F]fluoropicolinamide ([18F]P3BZA) and N-[2-(diethylamino)-ethyl]-4-[18F]fluorobenzamide ([18F]FBZA) in B16F10 or SK-MEL-3 subcutaneous tumor bearing mouse model (7.4MBq). The static images at 60 min were acquired for 10 min. Results: Cell uptakes of [18F]DMPY2 was >103 fold higher in B16F10 (mouse melanoma) cells than in negative control cells. Biodistribution studies revealed strong tumor uptake and retention of [18F]DMPY2 (24.8% injected dose per gram of tissue [ID/g] at 60 min) in B16F10 xenografts. MicroPET imaging of [18F]DMPY2 demonstrated strong tumoral uptake/retention and rapid washout, resulting in excellent tumor-to-background contrast in B16F10 xenografts. Furthermore, the tumor-to-liver ratio of [18F]DMPY2 was over 11.0-fold and 14.7-fold higher than that of [18F]P3BZA and [18F]FBZA, respectively ([18F]DMPY2: 36.29 ± 3.55; [18F]P3BZA: 3.28 ± 1.34; [18F]FBZA: 2.47 ± 0.24; *P