Figure 3.

HSV1-tk was fused in-frame with the hygromycin phosphotransferase gene and expressed as a fusion protein. Through imaging of HSV1-tk reporter gene expression using [¹⁸F]FHBG, which is an ¹⁸F-radiolabeled analog of the anti-herpes drug penciclovir, [¹⁸F]FHBG trapping in the brain tumor could be imaged, which corresponds to CTL accumulation. The [¹⁸F]FHBG PET imaging was performed in a patient with a recurrent right frontoparietal glioblastoma (A) before and (B) 1 week after tumor-specific HSV1tk-transduced CAR T-cell infusions. Allogeneic CAR T cells and IL-2 were injected intratumorally (red arrows). Tumor recurrence was monitored by T1W MRI (top panels). The [¹⁸F]FHBG PET images were fused with MR images (bottom panels), and 3D volumes of interest were drawn using a 50% [¹⁸F]FHBG SUVmax threshold (outlined in yellow). (C) Voxel-wise analysis of[¹⁸F]FHBG SUV in pre- and post-CTL infusion scans. Reproduced with permission from [111] © American Association for the Advancement of Science (2017). CTL, cytotoxic T lymphocyte; [¹⁸F]FHBG, 9-[4-[¹⁸F]fluoro-3-(hydroxymethyl)butyl] guanine; HSV1-tk, herpes simplex virus 1-thymidine kinase; SUV, standard uptake value; 3D, three-dimensional; T1W, T1-weighted.