Antilipolytic drugl boosts glucose metabolism in prostate cancer

Introduction: The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PO) prostate cancer (PCa) xenografts. Methods: Subcutaneous tumors were produced in nude mice by injection of PC3 and CWR22Rv1 PCa cells. The mice were divided into two groups (Acipimox vs. controls). Acipimox (50 mg/kg) was administered by oral gavage 1 h before injection of tracers. 1 h after i.v. co-injection of 8.2 MBq (222 +/- 6.0 mu Ci) (18) F-FDG and similar to 0.0037 MBq (0.1 mu Ci) C-14-acetate, (18) F-FDG imaging was performed using a small-animal PET scanner. Counting rates in reconstructed images were converted to activity concentrations. Quantification was obtained by region:of-interest analysis using dedicated software. The mice were euthanized, and blood samples and organs were harvested. (18) F radioactivity was measured in a calibrated gamma-counter using a dynamic counting window and decay correction. C-14 radioactivity was determined by liquid scintillation counting using external standard quench corrections. Counts were converted into activity, and percentage of the injected dose per gram (%ID/g) tissue was calculated. Results: FDG biodistribution data in mice with PO xenografts demonstrated doubled average %ID/g tumor tissue after administration of Acipimox compared to controls (7.21 +/- 1.93 vs. 3.59 +/- 1.35, P=0.02). Tumor-to-organ ratios were generally higher in mice treated with Acipimox. This was supported by PET imaging data, both semi-quantitatively (mean tumor FDG uptake) and visually (tumor-to-background ratios). In mice with CWR22Rv1 xenografts there was no effect of Acipimox on FDG uptake, either in biodistribution or PET imaging. C-14-acetate uptake was unaffected in PO and CWR22Rv1 xenografts. Conclusions: In mice with PO PCa xenografts, acute administration of Acipimox increases tumor uptake of (18) F-FDG with general improvements in tumor-to-background ratios. Data indicate that administration of Acipimox prior to (18) F-FDG PET scans has potential to improve sensitivity and specificity in patients with castration-resistant advanced PCa. (C) 2013 Elsevier Inc. All rights reserved.