Ketone body utilization by breast and prostate tumors

1478 Objectives: Cancer cells can utilize ketone bodies as alternate fuels to meet their requirements. A relation has been observed between the availability of the ketone bodies and their uptake by tumor cells. The objective of this study was to evaluate 11C-acetoacetate, a ketone body, as a potential tracer to measure ketone body utilization by breast and prostate tumors. Methods: The biological properties of 11C-acetoacetate were evaluated on three differents cell cultures : MC7-L1 and MC4-L2 (a native murine model of breast cancer) and PC-3 (human prostate cancer cells). MC7-L1 and MC4-L2 cells were implanted in immunocompetent BALB/c mice whereas PC-3 cells were implanted to BALB/c nu/nu mice. The tumors were grown to a diameter of 5-7 mm. 11C-acetoacetate was synthesized by reacting an enolate anion of acetone with 11C-CO2, followed by hydrolysis and ion-exchange HPLC purification. The animals were sacrificed 5, 15, 30 and 60 min following injection of 200-300 µCi of 11C-acetoacetate. The organs were taken and immediately weighed and counted to evaluate the percentage of the injected dose accumulated per gram of tissue (%i.d./g tissue). Results: The uptake of 11C-acetoacetate was optimal between 15 and 30 minutes, with maximal uptake of 2,72 %i.d./g. for the MC7-L2 tumors, 2.42 %i.d./g for the MC4-L1 and 3.05 %i.d./g for the PC3 tumors. The peak tumor to muscle ratios were obtained between 30 and 60 minutes : 4.5 ± 2.27 for tumor MC7-L1, 3,62 ± 1.28 for tumor MC4-L2 and 3.01 ± 0.27 for tumor PC-3. In all tumors, a transient uptake was observed followed by a progressive decrease in tumor radioactivity. The tumor retention of 11C-acetate was slightly lower than 11C-acetoacetate in these models, but not significantly. Further studies are underway to assess the impact of dietary intake (ketogenic diet) on tumor ketone body utilization. Conclusions: We observed a moderate uptake of a 11C-acetoacetate in breast and prostate tumors, suggesting that ketone bodies are actively used as complementary fuels to supply tumor energy requirements. While no cumulative trapping was noted in these models, further experiments are ongoing to compare this tracer to 11C-acetate for the detection of slower-growing tumors.