The preliminary feasibility studies of 4-[¹⁸F] fluorobutyric acid and its methyl ester as PET imaging agents

Objective: To synthesize 4-[¹⁸F] fluorobutyric acid and its methyl ester automatically using PET-MF-2V-IT-I multifunction synthesizer and to evaluate their feasibility as PET imaging agents. Methods: The precursor, methyl 4-bromobutyrate was fluorinated with ¹⁸F^-. The intermediate, methyl 4-[¹⁸F] fluorobutyrate was separated by high pressure liquid chromatography. The components which retention time was from 6.8 to 7.8 min were collected. The components were heated with NaOH solution at 115 ℃ for 10 min to hydrolyze, and then neutralized with HCl solution. The product, 4-[¹⁸F] fluorobutyric acid was obtained. The components were diluted and passed through a C18 cartridge, which was washed with 20 ml water then. The product, methyl 4-[¹⁸F] fluorobutyrate was obtained after 0.5 ml ethanol eluted the cartridge and was diluted with saline. The quality controls of both products were done. The clarity was tested visually, the pH value was tested with precise pH paper, and the radiochemical purity and stability were also measured. 4-[¹⁸F] fluorobutyric acid (7.4∼11.1 MBq) was injected into the C57BL/J mice via tail vein for micro PET imaging at 30 min time-point. Results: The whole synthetic procedure periods of 4-[¹⁸F] fluorobutyric acid and methyl 4-[¹⁸F] fluorobutyrate were 40 min and 20 min separately. The radiochemical yields of the two products were about 35% and 50% (both decay uncorrected) respectively. The pH values were 6.5 and 7.1. The radiochemical purities were both > 95%. Both the product solutions were clear and no particles. Defluorination was observed in these two product solutions 0.5 h later at room temperature. The micro PET imaging showed that the uptake of spine was clearly, which indicated that the imaging agent was defluorinated in vivo, the uptake of intestine was also higher. Conclusion: 4-[¹⁸F] fluorobutyric acid and its methyl ester could be automatically synthesized on PET-MF-2V-IT-I multifunction synthesizer simply and rapidly. The synthetic yield, radiochemical purity were high. But for their instabilities at room temperature, the two agents were not suitable for further studies as PET imaging agents. But the micro PET imaging suggested the analogs of [¹⁸F] fluorobutyric acid may have its potential in diagnosis of intestinal diseases. (authors)