Similar to other major metabolic networks, nucleotide metabolism consists of redundant and convergent biosynthetic pathways. Thus, nucleotides can be produced both de novo, from glucose and amino acids, and by salvage pathways, via scavenging and re-utilization of preformed nucleosides and nucleobases. The differential utilization of de novo and salvage nucleotide biosynthetic pathways in normal and malignant is poorly understood. We are studying this process in lymphocytes and cancer cells using newly developed mass spectrometry and positron emission tomography (PET) approaches. Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside salvage pathway, is significantly upregulated following T cell activation and therefore represents a promising PET imaging target. PET probes for dCK have been previously developed by our group and shown to be effective in mice but their specificity and sensitivity in humans remained suboptimal. Recently we have identified [18F]CFA (2-chloro-2′-deoxy-2′-[18F]fluoro-9-β-D-arabinofuranosyl-adenine) as a suitable third generation nucleoside analog probe for clinical dCK PET imaging. First-in-human [18F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The potential use of [18F]CFA PET for imaging systemic immune activation induced by various cancer immunotherapies will be discussed.
Citation Format: Caius G. Radu. PET imaging of the immune system using new nucleoside analog probes. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr IA20.