In vivo responses of human A375M melanoma to a σ ligand: 18F-FDG PET imaging

Abstract

σ-ligands can kill tumor cells. Previously we have shown that a short in vitro incubation of C6 tumor cells with σ-ligands (24 h) results in a dose-dependent increase of cellular 18F-FDG uptake and that the magnitude of this increase is predictive of subsequent cell death. Here, we aimed to assess whether the σ-ligand rimcazole inhibits growth of A375M melanoma xenografts in nude mice and whether rimcazole treatment changes 18F-FDG uptake in vivo. Methods: Athymic mice were inoculated with A375M melanoma cells. After 2 wk, tumors had reached a size of 41 ± 6 mm3. We then started a 14-d treatment schedule with daily drug dosing. Control animals were injected with water and treated animals with rimcazole (26 mg/ kg) in water. Three small-animal PET scans with 18F-FDG were obtained: on days 0, 7, and 14 of treatment. After the last scan, animals were terminated, and a biodistribution study was performed. Results: Rimcazole treatment resulted in a greater than 4-fold reduction of tumor weight in comparison to controls at day 14 (100 ± 26 vs. 436 ± 117 mg, respectively, P < 0.03). Treatment did not affect the levels of (nonradioactive) glucose in blood, σ-1 and σ-2 receptor expression in the tumor, animal weight, behavior, or appearance. Antitumor activity of rimcazole was accompanied by a transient increase of the tumor uptake of 18F-FDG (measured at day 7). Significant increases of 18F-FDG uptake at day 14 were observed in the liver and pancreas. Conclusion: Rimcazole strongly inhibited the growth of A375M melanoma xenografts. This growth inhibition is accompanied by an early increase of 18F-FDG uptake in the tumor. COPYRIGHT © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.