Abstract SY03-02: Tumor metabolic phenotyping and treatment stratification by positron emission tomography

The ability to noninvasively measure key metabolic pathways in living subjects may assist the development of new, more efficacious therapies against cancer. Here we show that two new positron emission tomography (PET) probes, 1-(2′-deoxy-2′-18F-fluoro-β-D-arabinofuranosyl)cytosine (18F-FAC) and 1-(2′-deoxy-2′-18F-fluoro-β-L-arabinofuranosyl)-5-methylcytosine (L-18F-FMAC), detect distinct phenotypic signatures of tumor nucleoside metabolism. 18F-FAC and L-18F-FMAC accumulation in tumors measured in vivo by PET is indicative of the activities of deoxycytidine kinase (dCK) and cytidine deaminase (CDA), two key enzymes in nucleic acid metabolism. Metabolic subtypes detected by 18F-FAC and L-18F-FMAC were shown to correspond to the differential utilization by cancer cells of the nucleoside salvage pathway to generate and maintain deoxyribonucleotide pools required to sustain tumor growth. We also show that the metabolic subtypes defined by 18F-FAC and L-18F-FMAC PET measurements correlate with markedly distinct sensitivities to therapeutic interventions. These findings support the utility of PET-based phenotyping of tumor nucleoside metabolism for treatment stratification in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY03-02. doi:10.1158/1538-7445.AM2011-SY03-02