%0 Journal Article %A Hui Liu %A Yuxiang Han %A Jiyuan Li %A Qunfeng Fu %A Chunhong Wang %A Zhibo Liu %T An 18F-Alanine derivative serves as an ASCT2 marker for cancer imaging %D 2018 %J Journal of Nuclear Medicine %P 62-62 %V 59 %N supplement 1 %X 62Objectives: Gastric cancer is a great challenge for cancer therapy because of its high lethality and morbidity. It is well known that 18F-FDG PET scan has been successfully used in the diagnosis, staging, and monitoring the treatment of many types of cancers. However, gastric cancer is usually accompanied by chronic gastritis, and inflammation commonly resolved by FDG results in false positive cancer diagnosis. Therefore, to improve clinical diagnostic and prognostic approaches, novel biomarkers with better specificity are in urgent need for gastric cancer imaging. Recently, amino acids derivatives have been well established for diagnosis of a variety of cancer using positron emission tomography (PET). Herein, we developed a 18F-labeled alanine derivative through displacing its carboxylate by trifluoroborate as a selective ASCT2 marker for gastric cancer imaging. Methods: An alanine derivative that displaced its carboxylate by trifluoroborate was synthesized to mimic the natural L-alanine, of which the metabolism relies on Alanine-Serine-Cysteine-Threonine transporter type 2 (ASCT2). One-step 18F-19F exchange approach was adopted in radiolabeling, while the quality control was conducted by both radioTLC and HPLC. The stability assay of 18F-Ala-BF3 was performed both in PBS and FBS in vitro. PET-CT scan and in vitro bio-distribution studies were assessed in mice beraring BGC-823 xenografts on the right shoulder and inflammation in the caudal thigh muscles of the left hindlimb. PET imaging was implemented 48 hours (18F-FDG) and 72 hours (18F-Ala-BF3) following turpentine injection. Results: 18F-Ala-BF3 was firstly evaluated in healthy FVB/N mice in vivo, exhibiting rapid renal clearance with almost negligible uptake in stomach (1.53 ± 0.31 %ID/g). Notable uptake was observed in thyroid (3.71 ± 0.49 %ID/g, 40 min post injection), of which the uptake was significantly inhibited by co-injecting with natural L-alanine. As expected, dynamic PET-CT scan revealed the optimal time window for tumor imaging, it was between 40 min and 60 min post injection, when the BGC-823 xenografts uptake was 5.49 ±1.47 %ID/g, and the tumor-to-stomach, tumor-to-blood, tumor-to-muscle, and tumor-to-brain ratios were 3.27 ± 1.53, 3.80 ± 1.48, 3.47 ± 1.48, and 6.20 ± 1.47, respectively. Remarkably, 18F-Ala-BF3 accumulated specifically in BGC-823 xenografts to give high tumor-to-background contrast at 45 min post injection. The average uptake of tumor and inflammation tissue was 5.23 ± 0.93 %ID/g and 2.70 ± 1.03 %ID/g, while 18F-FDG exhibited high uptake both in tumor and inflammation tissue, and the corresponding uptake was 4.93 ± 0.85 %ID/g and 5.83 ± 1.94 %ID/g. Conclusion: The 18F-Ala-BF3 was successfully synthesized through one-step 18F-19F isotope exchange with fine specific activity and good radiochemical yield. Following in vitro bio-distribution and in vivo PET imaging in gastric tumor xenografts bearing mice and healthy mice revealed high tumor to normal tissue rate consist with fine tumor imaging of 18F-Ala-BF3. This study shed light on ASCT2 as a cancer biomarker for clinical diagnosis, and emphasized the usefulness of BAAs in tumor PET imaging. 18F-Ala-BF3 represents a useful molecular platform for tumor diagnosis. %U