Preclinical study of an ¹⁸F-labeled glutamine derivative for cancer imaging

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.

[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.

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.

[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.