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Oncology-Basic Science: Basic ScienceNew Targets |
1 Radiology, UMDNJ, Newark, New Jersey
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413
Objectives: Prostate cancer is characterized by slow glycolysis and low FDG avidity on PET imaging. We hypothesize that fatty acid rather than glucose metabolism is the dominant bioenergetic pathway in prostate cancer.
Methods: 2 malignant (LNCaP and PC-3) and 1 benign (EWPE-1) prostate cell lines were assayed for in vitro uptake of radiolabeled glucose analogs (3H-FDG, 18F-FDG) and a long-chain fatty acid (3H-palmitic acid). Uptake was standardized to viable cell numbers and normalized to activity added to medium.
Results: 1. Uptake of fatty acid in the prostate cells is a time dependent, dynamic process. 2. Nonspecific protein modifier HgCl2 has an inhibitory effect on fatty acid uptake, suggestive of membrane receptor mediated uptake. 3. Uptake of palmitic acid in all 3 prostate cell lines is significantly higher than that of glucose (on 1 hour incubation experiments: 4.09 ± 0.36 vs. 0.20 ± 0.028 in LNCaP, 4.24 ± 1.31 vs. 0.195 ± 0.007 in PC-3 and 4.27 ± 0.37 vs. 0.12 ± 0.084 in EWPE1). 4. In malignant cell lines, neither FDG nor fatty acid uptake was quantitatively higher than in the benign line.
Conclusions: 1. Prostate tissue is characterized by dominant fatty acid metabolism as its energy source. 2. Malignant prostate cell lines have neither increased fatty acid nor glucose metabolism compared to a benign cell line, consistent with a slow rate of metabolism and growth. 3. Future development of new diagnostic and therapeutic approaches in prostatic cancer should focus on fatty acid metabolism. Fatty acid imaging may be useful in detection of recurrence and metastasis, but not in differentiating malignant from benign prostate tissue.
Research Support: SNM Pilot Research Grant
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