2- 18F-氟丁酸作为PET/CT显像剂可行性的初步研究

目的:设计合成 18F标记的新型短链脂肪酸代谢型显像剂2- 18F-氟丁酸（2- 18F-FBA），对其作为肿瘤PET/CT显像剂进行初步研究。 方法:前体2-溴丁酸甲酯通过 18F-亲核取代反应实现放射性标记，中间体2- 18F-氟丁酸甲酯经高效液...

The preliminary study on the feasibility of 2-18F-fluorobutyric acid as a PET/CT agent

Objective To design and synthesize a new type of 18F-labeled short-chain fatty acid imaging agent, namely 2-18F-fluorobutyric acid (2-18F-FBA) and to evaluate its use as a tumor PET/CT imaging agent. Methods Methyl 2-bromobutyrate as a precursor was radiolabeled via 18F? nucleophilic substitution reaction. 2-18F-Methyl fluorobutyrate formed as an intermediate was separated through high performance liquid chromatography. Components with a retention time of 16–18 min were collected. After being diluted with 20 mL of water, the components were passed through a C18 column, rinsed with 10 mL of water, and blow-dried. The intermediate was adsorbed and hydrolyzed with 1 mL of NaOH solution to obtain 2-18F-FBA. The clarity of the product was visually inspected, and its pH value was determined with pH paper. Its radiochemical purity and stability were also measured. Institute of cancer research healthy mice were injected with 2-18F-FBA (0.2 mL, 7 MBq) through the tail vein to examine the biological distribution of 2-18F-FBA. S180 sarcoma tumor-bearing mice were subjected to micro-PET/CT imaging and performed image analysis, Calculated SUV_max. Biological distribution in various tissues and organs at different time points was compared via Student's t test. Results The whole preparation time of 2-18F-FBA was 40 min, the radiochemical yield was (40±5)% (corrected by time), and radiochemical purity was >98%. The product solution was clear and did not contain particles. Its pH value was 7.2, and its stability was good in vivo and in vitro. Biological distribution in vivo showed that the liver, heart and lungs had significant radioactive uptake after injected of 2-18F-FBA 5 min. Brain tissue had low uptake at all time points. Radioactive uptake gradually decreased with time and stabilized after 60 min. The bone uptake rate did not change significantly with time, and the radioactive uptake rate 5 min after the injection of the imaging agent did not significantly differ from the rates at 30 min and 90 min (t=1.532, 1.104; both P>0.05). The micro-PET/CT image of S180 sarcoma tumor-bearing mice revealed that the radioactive uptake in the tumor was significant 30 min after 2-18F-FBA was injected. Conversely, the uptake of the surrounding tissues was low at this time point, and the tumor uptake reached the maximum after 60 min, SUV_max=1.90±0.03. The liver, intestines, and other abdominal organs also had radioactivity uptake. Conclusions 2-18F-FBA has a short synthesis time and a high radiochemical yield. It is a new fatty acid metabolite that can be used as an imaging agent with potential for application in tumor detection.