Development of a Radiotracer for PET Imaging of the SNAP Tag

Cell therapies have progressed to cures for hematopoietic disorders, neurodegenerative diseases, and cancer. However, only some patients can benefit from cell therapies even with prior screening. Due to the limited clinical methods to monitor the in vivo therapeutic functions of these transferred cells over time, the uncertain prognosis is hard to attenuate. Positron emission tomography (PET) cell tracking can provide comprehensive dynamic and spatial information on the proliferation status and whole-body distribution of the therapeutic cell. In this work, we designed and synthesized the first SNAP-tagged PET radiotracer. SNAP tag is an O ⁶-alkylguanine-DNA alkyltransferase that can form an irreversible bond with ¹⁸F-BG-surface for in vivo cell tracking based on a reporter gene system. ¹⁸F-BG-surface was obtained by the F-Al radiolabeling method in 32 ± 7% radiochemical yield and showed a high in vitro stability in mouse serum. SNAP-tagged cells could be selectively targeted by ¹⁸F-BG-surface both in vitro (4.81 ± 0.08%AD/10⁶ cell vs 2.26 ± 0.10%AD/10⁶ cell) and in vivo (1.90 ± 0.05 vs 0.55 ± 0.02% ID/g, p < 0.01).