Cong Li1, Hui Liu2, Dongban Duan2, Zhenhan Zhou2, Zhibo Liu3. 1. Peking University-Tsinghua University Center for Life Sciences, Beijing 100871, China. 2. Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. 3. Peking University-Tsinghua University Center for Life Sciences, Beijing 100871, China; Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: zbliu@pku.edu.cn.
Abstract
INTRODUCTION: The emerging evidence that demonstrated the extra-demand of glutamine for cancer surviving strongly called for the development of PET tracer for imaging glutamine uptake in cancer. In this work, [18F]Gln-BF3 as a natural glutamine derivative was synthesized to explore its potential application of imaging glutamine uptake for cancer diagnosis. METHODS: [18F]Gln-BF3 was prepared by deprotection of purified precursor trityl-Gln-BF3 (amide bond protected with triphenylmethyl group) using TFA and radiolabeled using 18F-19F isotope exchange protocol. PET imaging and biodistribution studies were conducted in Balb/c mice bearing 4T1 xenograft. RESULTS: Gln-BF3 was identified with HRMS ([M-H]- = 169.0765). [18F]Gln-BF3 was radiolabeled in high radiochemical yield (RCY > 25%) and characterized with Radio-HPLC-MS. Preliminary PET imaging showed the radioactivity was fast cleared from muscle tissue and excreted mainly via the renal pathway. PET study demonstrated that uptake of [18F]Gln-BF3 in 4T1 xenografts was significant. 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 was radiolabeled in a "kit-like" manner and showed notable and tumor-selective uptake in tumor-bearing animal models, suggesting that this new strategy of radiolabeling amino acid provided a promising solution for the future development of glutamine-derived PET tracers.
INTRODUCTION: The emerging evidence that demonstrated the extra-demand of glutamine for cancer surviving strongly called for the development of PET tracer for imaging glutamine uptake in cancer. In this work, [18F]Gln-BF3 as a natural glutamine derivative was synthesized to explore its potential application of imaging glutamine uptake for cancer diagnosis. METHODS: [18F]Gln-BF3 was prepared by deprotection of purified precursor trityl-Gln-BF3 (amide bond protected with triphenylmethyl group) using TFA and radiolabeled using 18F-19F isotope exchange protocol. PET imaging and biodistribution studies were conducted in Balb/c mice bearing 4T1 xenograft. RESULTS:Gln-BF3 was identified with HRMS ([M-H]- = 169.0765). [18F]Gln-BF3 was radiolabeled in high radiochemical yield (RCY > 25%) and characterized with Radio-HPLC-MS. Preliminary PET imaging showed the radioactivity was fast cleared from muscle tissue and excreted mainly via the renal pathway. PET study demonstrated that uptake of [18F]Gln-BF3 in 4T1 xenografts was significant. 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 was radiolabeled in a "kit-like" manner and showed notable and tumor-selective uptake in tumor-bearing animal models, suggesting that this new strategy of radiolabeling amino acid provided a promising solution for the future development of glutamine-derived PET tracers.