Authors: Biti, A., Fraguas-Sánchez, A.I., & Sarparanta, M. University of Helsinki Background Adoptive cell therapy is a promising mode of cancer therapy employing tumor infiltrating lymphocytes (TILs) with a limited success to hematologic cancers and melanoma.1 Molecular imaging strategies based on bioorthogonal chemistry and metabolic glycoengineering for in vivo tracking of TILs provide advantages compared to conventional techniques.2 Aims The aim of this study is to develop a new radiolabeling method for TILs without impairment of their antitumor and homing properties by using a Staudinger ligation between a perfluoroaryl azide tag3 on the surface of murine OT-I lymphocytes installed by metabolic glycoengineering and novel fluorine-18 radiolabeled phosphine reagents. Methods The PFAA-modified D-mannosamine is synthesized according to a reported procedure. The phosphine reagents present a linker and the NODAGA radiochelator and are synthesized by using common organic reactions. The radiolabeling with [18F]aluminum fluoride (AlF) requires in situ synthesis of [18F]AlF starting from saline-eluted [18F]fluoride ion and aluminum chloride (AlCl3). Results and Conclusion This labeling method eliminates the drying step needed for most [18F]F− labeling methods. Furthermore, Al18F complexes are hydrophilic and can be used for the radiolabeling of sensitive targets such as cells in aqueous systems. This could be a method towards the radiolabeling of TILs without genetic manipulation. References 1. Schietinger, A., et al., Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis. Immunity, 2016. 45(2): p. 389-401.2. Rossin, R., et al., Diels–Alder Reaction for Tumor Pretargeting: In Vivo Chemistry Can Boost Tumor Radiation Dose Compared with Directly Labeled Antibody. Journal of Nuclear Medicine, 2013. 54(11): p. 1989-1995.3. Sundhoro, M., et al., Perfluoroaryl Azide Staudinger Reaction: A Fast and Bioorthogonal Reaction. Angewandte Chemie International Edition, 2017. 56(40): p. 12117-12121.
