Production of 2-18F-fluorobutyric acid as a PET imaging agent for prostate cancer
- VernacularTitle:1-[18F]氟代乙基吲哚丙酸作为PET显像剂可行性的初步研究
- Author:
Weixuan DONG
1
;
Kaixin QIN
2
;
Cong SHEN
1
;
Dongmei SHI
2
;
Wenhao HU
2
;
Xiaoyi DUAN
1
Author Information
- Publication Type:Journal Article
- Keywords: 1-[18F]-fluoroethyl-indole propionic acid (1-[18F]-IPA); radiochemistry; micro-PET/CT; molecular probe
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):1020-1026
- CountryChina
- Language:Chinese
- Abstract: [Objective] In view of the crucial role of indole propionic acid in the treatment of tumor immune checkpoint blockade and further revealing its mechanism, our study intended to design and synthesize 1-[18F]-fluoroethyl-indole propionic acid (1-[18F]-IPA), and evaluate it as a tumor PET imaging agent. [Methods] The precursor 1-(2-p-toluenesulfonic acid oxygen ethyl)-methyl indole propionate underwent nucleophilic substitution reaction with 18F-. The crude product was separated and purified by high-performance liquid chromatography and the intermediates were collected. Finally, 1-[18F]-IPA was obtained by hydrolysis. The clarity of the product was measured by visual inspection, the pH value was determined by precision test paper, and the radiochemical purity and stability were determined by high-performance liquid chromatography. In order to determine the biodistribution of 1-[18F]-IPA in normal mice, ICR mice were intravenously injected with 1-[18F]-IPA (0.2 mL, 7 MBq), and sacrificed at 5, 15, 25, 45, 75 and 120 min and dissected. Micro-PET imaging was performed and analyzed in BxPC-3 tumor-bearing nude mice. Student t test was used to compare the biodistribution of tissues and organs at different time points. [Results] The total preparation time of 1-[18F]-IPA was 35-40 min, the radiochemical yield was (45±5)%, and the radiochemical purity was more than 95%. The product solution was clear without particles, and the pH value was 6.5, which had good stability in vitro and in vivo. The results of biodistribution in healthy ICR mice showed that except for the brain, 1-[18F]-IPA had a certain uptake in all major organs, with the most obvious uptake in the liver, gallbladder and kidneys. The radioactivity in the gallbladder gradually increased with time and reached (39.86±6.56)%ID/g at 120 min, but bone uptake did not change significantly with time. Micro-PET/CT showed that there was radioactive uptake at the tumor 30 min after injection of 1-[18F]-IPA in Dutch BxPC-3 nude mice, but it was not obvious. At this time, SUVmax was about 55.18±14.62. Consistent with the results of biodistribution, the brain uptake was low at each time point. [Conclusion] In summary, 1-[18F]-IPA with short preparation time and high yield is expected to be a tool to probe tryptophan indole metabolism pathway and further reveal tumor immune resistance.
