Journal
MOLECULAR IMAGING AND BIOLOGY
Volume 17, Issue 4, Pages 529-538Publisher
SPRINGER
DOI: 10.1007/s11307-014-0814-4
Keywords
CPT1A; Etomoxir; FDG-PET; Glycolysis; Fatty acid; Beta-oxidation; Mitochondria
Funding
- ACS [PF-117219, IRG-57-001-50]
- NIH [K01CA168934, CA102514]
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Prostate cancer (PCa) is the second most common cause of cancer-related death among men in the United States. Due to the lipid-driven metabolic phenotype of PCa, imaging with 2-deoxy-2-[F-18]fluoro-d-glucose ([F-18]FDG) is suboptimal, since tumors tend to have low avidity for glucose. We have used the fat oxidation inhibitor etomoxir (2-[6-(4-chlorophenoxy)-hexyl]oxirane-2-carboxylate) that targets carnitine-palmitoyl-transferase-1 (CPT-1) to increase glucose uptake in PCa cell lines. Small hairpin RNA specific for CPT1A was used to confirm the glycolytic switch induced by etomoxir in vitro. Systemic etomoxir treatment was used to enhance [F-18]FDG-positron emission tomography ([F-18]FDG-PET) imaging in PCa xenograft mouse models in 24 h. PCa cells significantly oxidize more of circulating fatty acids than benign cells via CPT-1 enzyme, and blocking this lipid oxidation resulted in activation of the Warburg effect and enhanced [F-18]FDG signal in PCa mouse models. Inhibition of lipid oxidation plays a major role in elevating glucose metabolism of PCa cells, with potential for imaging enhancement that could also be extended to other cancers.
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