Abstract
1256
Objectives: Glutamine is one of the most needed nutrients for a broad scope of cancer cell lines. Significant efforts have been devoted to the exploration of novel tumor PET tracers based on glutamine addiction. Herein, we developed a glutamine derivative ([18F]Gln-BF3) to image glutamine addiction in various types of tumor.
Methods: [18F]Gln-BF3 was prepared by deprotection of purified precursor trityl-Gln-BF3 (primary amide bond protected with triphenylmethyl group) using TFA and radiolabeled using 18F-19F isotope exchange protocol. PET imaging studies were conducted in Nu/Nu mice bearing U87MG xenograft and BGC823 xenograft, C57 mice bearing MC38 xenograft, NSG mice bearing GH3 and Balb/c mice bearing 4T1 xenograft. Biodistribution studies were performed in Balb/c mice bearing 4T1 xenograft.
Results: Gln-BF3 was identified with HPLC-MS (M-1=169) and radiolabeled in high radiochemical yield (RCY>30%). Preliminary PET imaging showed the radioactivity was fast cleared from muscle tissue and excreted mainly via the renal pathway. Comparative [18F]Gln-BF3 PET studies demonstrate that uptake of [18F]Gln-BF3 in 4T1 and GH3 xenografts are substantially higher than those in U87MG, MC38 and BGC823 xenografts(as shown in Figure). The biodistribution results of [18F]Gln-BF3 in mice bearing 4T1 xenograft indicate a tumor-to-muscle ratio of 2.58 ± 0.64(n=4) and a 6.29 ± 0.42% ID/g(n=4) uptake in tumor at 45 min post injection. Conclusion: [18F]Gln-BF3 showed discriminating uptake over different types of tumor and also considerable defluorination in vivo. Further investigation should be focused on the understanding of defluorination and chemical optimization of Gln-BF3. <!--EndFragment-->