18f-fluoroethyl-l-tyrosine and Neoplasms

A new synthesis of O-(2-[(18)F]fluoroethyl)-L-tyrosine [(18)F]FET was developed using a NanoTek® microfluidic synthesis system (Advion BioSciences, Inc.). Optimal reaction conditions were studied through screening different reaction parameters like temperature, flow rate, reaction time, concentration of the labeling precursor, and the applied volume ratio between the labeling precursor and [(18)F]fluoride. [(18)F]FET was obtained after HPLC purification with 50% decay-corrected radiochemical yield starting from as little as 40 μg of labeling precursor. Small animal PET studies in EMT-6 tumor bearing mice showed radioactivity accumulation in the tumor (SUV(60min) 1.21±0.2) resulting in an slightly increasing tumor-to-muscle ratio over time.

Topics: Animals; Chromatography, High Pressure Liquid; Fluorine Radioisotopes; Half-Life; Isotope Labeling; Mice; Mice, Inbred BALB C; Microfluidics; Neoplasm Transplantation; Neoplasms; Positron-Emission Tomography; Radiopharmaceuticals; Tissue Distribution; Tyrosine

Two novel pyrazolo[1,5-a]pyrimidine derivatives, 7-(2-[(18)F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([(18)F]FEMPPC, [(18)F]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[(18)F]fluoro-4-nitrobenzamide ([(18)F]FCMPPN, [(18)F]2), have been designed and successively labeled with (18)F by the nucleophilic substitution employing tosylate and nitryl as leaving groups, respectively. The radiochemical synthesis of both compounds was completed within 60min with final high-performance liquid chromatography purification included. The corresponding radiochemical yields (without decay correction) were approximately 35% and 30%, respectively. Meanwhile, we compared the uptake characteristics of [(18)F]1 and [(18)F]2 with those of [(18)F]FDG and L-[(18)F]FET in S180 tumor cells. Furthermore, the tumor uptake of [(18)F]1 and [(18)F]2 was assessed in mice bearing S180 tumor and compared with [(18)F]FDG and L-[(18)F]FET in the same animal model. In vitro cell uptake studies showed [(18)F]1 had higher uptake than [(18)F]FDG, [(18)F]2 and L-[(18)F]FET over the 2h period. In ex vivo biodistribution showed tumor/brain uptake ratios of [(18)F]2 were 12.35, 10.44, 8.69 and 5.13 at 15 min, 30 min, 60 min and 120 min post-injection, much higher than those of L-[(18)F]FET (2.43, 2.54, 2.93 and 2.95) and [(18)F]FDG (0.59, 0.61, 1.02 and 1.33) at the same time point. What's more, the uptake of [(18)F]1 in tumor was 1.88, 4.37, 5.51, 2.95 and 2.88 at 5 min, 15 min, 30 min, 60 min and 120 min post-injection, respectively. There was a remarkable increasing trend before 30 min. The same trend was present for L-[(18)F]FET before 30 min and [(18)F]FDG before 60 min. Additionally, the tumor/brain uptake ratios of [(18)F]1 were superior to those of [(18)F]FDG at all the selected time points, the tumor/muscle and tumor/blood uptake ratios of [(18)F]1 at 30 min were higher than those of L-[(18)F]FET at the same time point. MicroPET image of [(18)F]1 administered into S180 tumor-bearing mouse acquired at 30 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggest that compound [(18)F]1 could be a new probe for PET tumor imaging.

Topics: Animals; Fluorine Radioisotopes; Mice; Molecular Conformation; Neoplasms; Positron-Emission Tomography; Pyrazoles; Pyrimidines; Stereoisomerism; Tissue Distribution

This article reported the synthesis and bioevaluation of two [(18)F] labeled benzimidazole derivatives, 4-(5-(2-[(18)F] fluoro-4-nitrobenzamido)-1-methyl-1H-benzimidazol-2-yl) butanoic acid ([(18)F] FNBMBBA, [(18)F]a1) and 3-(2-fluoroethyl)-7-methyl-2-propyl-3H-benzimidazole-5-carboxylic acid ([(18)F] FEMPBBA, [(18)F]b1) for PET tumor imaging. The preparation [(18)F] FEMPBBA was completed in 1h with overall radiochemical yield of 50-60% (without decay corrected). Biodistribution assay in S180 tumor bearing mice of both compounds were carried out, and the results are both meaningful. [(18)F] FEMPBBA which can be taken as a revision of [(18)F] FNBMBBA got an excellent result, and has significant advantages in some aspects compared with L-[(18)F] FET and [(18)F]-FDG in the same animal model, especially in tumor/brain uptake ratio. The tumor/brain uptake ratio of [(18)F] FEMPBBA gets to 4.81, 7.15, and 9.8 at 30min, 60min and 120min, and is much higher than that of L-[(18)F] FET (2.54, 2.92 and 2.95) and [(18)F]-FDG (0.61, 1.02, 1.33) at the same time point. The tumor/muscle and tumor/blood uptake ratio of [(18)F] FEMPBBA is also higher than that of L-[(18)F] FET at 30min and 60min. This result indicates compound [(18)F] FEMPBBA is a promising radiotracer for PET tumor imaging.

Topics: Animals; Antineoplastic Agents; Bendamustine Hydrochloride; Benzimidazoles; Chromatography, High Pressure Liquid; Female; Fluorine Radioisotopes; Indicators and Reagents; Isotope Labeling; Mice; Neoplasms; Nitrogen Mustard Compounds; Positron-Emission Tomography; Radiopharmaceuticals; Sarcoma 180; Solubility; Solvents; Tissue Distribution