University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen, The Netherlands.
J Nucl Med. 2013 Sep;54(9):1613-20. doi: 10.2967/jnumed.113.122655. Epub 2013 Aug 12.
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 (18)F-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 (18)F-FDG uptake in vivo.
Athymic mice were inoculated with A375M melanoma cells. After 2 wk, tumors had reached a size of 41 ± 6 mm(3). 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 (18)F-FDG were obtained: on days 0, 7, and 14 of treatment. After the last scan, animals were terminated, and a biodistribution study was performed.
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 (18)F-FDG (measured at day 7). Significant increases of (18)F-FDG uptake at day 14 were observed in the liver and pancreas.
Rimcazole strongly inhibited the growth of A375M melanoma xenografts. This growth inhibition is accompanied by an early increase of (18)F-FDG uptake in the tumor.
评估 σ-配体 rimcazole 是否能抑制裸鼠 A375M 黑素瘤异种移植瘤的生长，以及 rimcazole 治疗是否会改变体内 (18)F-FDG 的摄取。
将 A375M 黑素瘤细胞接种于无胸腺小鼠。2 周后，肿瘤大小达到 41±6mm(3)。我们随后开始了为期 14 天的治疗方案，每天给予药物。对照组动物注射水，治疗组动物注射 rimcazole（26mg/kg）。在治疗的第 0、7 和 14 天进行了 3 次小动物 PET 扫描，以摄取 (18)F-FDG。最后一次扫描后，处死动物并进行生物分布研究。
与对照组相比，rimcazole 治疗在第 14 天使肿瘤重量减少了 4 倍以上（分别为 100±26 和 436±117mg，P<0.03）。治疗并未影响血液中的（非放射性）葡萄糖水平、肿瘤中 σ-1 和 σ-2 受体的表达、动物体重、行为或外观。rimcazole 的抗肿瘤活性伴随着肿瘤摄取 (18)F-FDG 的短暂增加（在第 7 天测量）。在第 14 天，肝脏和胰腺的 (18)F-FDG 摄取显著增加。
rimcazole 强烈抑制了 A375M 黑素瘤异种移植瘤的生长。这种生长抑制伴随着肿瘤中 (18)F-FDG 摄取的早期增加。
