A subset (35%) of triple-negative breast cancers (TNBCs) expresses androgen receptor (AR) activity. However, clinical trials with antiandrogen drugs have shown limited efficacy, with about a 19% clinical benefit rate. We investigated the therapeutic enhancement of antiandrogens as radiosensitizers in combination with ¹⁸F-FDG in TNBC. Methods: We screened 5 candidate drugs to evaluate shared toxicity when combined with either ¹⁸F-FDG, x-rays, or ultraviolet radiation, at doses below their respective half-maximal inhibitory concentrations. Cytotoxic enhancement of antiandrogen in combination with ¹⁸F-FDG was evaluated using cell proliferation and DNA damage assays. Finally, the therapeutic efficacy of the combination treatment was evaluated in mouse tumor models of TNBC and prostate cancer. Results: Bicalutamide, an antiandrogen drug, was found to share similar toxicity in combination with either ¹⁸F-FDG or x-rays, indicating its sensitivity as a radiosensitizer to ¹⁸F-FDG. Cell proliferation assays demonstrated selective toxicity of combination bicalutamide-¹⁸F-FDG in AR-positive 22RV1 and MDA-MB-231 cells in comparison to AR-negative PC3 cells. Quantitative DNA damage and cell cycle arrest assays further confirmed radiation-induced damage to cells, suggesting the role of bicalutamide as a radiosensitizer to ¹⁸F-FDG–mediated radiation damage. Animal studies in MDA-MB-231, 22RV1, and PC3 mouse tumor models demonstrated significant attenuation of tumor growth through combination of bicalutamide and ¹⁸F-FDG in the AR-positive model in comparison to the AR-negative model. Histopathologic examination corroborated the in vitro and in vivo data and confirmed the absence of off-target toxicity to vital organs. Conclusion: These data provide evidence that ¹⁸F-FDG in conjunction with antiandrogens serving as radiosensitizers has utility as a radiotherapeutic agent in the ablation of AR-positive cancers.

三阴性乳腺癌 (TNBC) 的一个子集 (35%) 表达雄激素受体 (AR) 活性。然而，抗雄激素药物的临床试验显示疗效有限，临床获益率约为 19%。我们研究了抗雄激素作为放射增敏剂与¹⁸ F-FDG 在 TNBC 中的治疗增强作用。方法：我们筛选了 5 种候选药物，以评估与¹⁸ F-FDG、X 射线或紫外线辐射组合时的共同毒性，剂量低于各自的半最大抑制浓度。抗雄激素联合^{18增强细胞毒性}使用细胞增殖和 DNA 损伤测定法评估 F-FDG。最后，在 TNBC 和前列腺癌的小鼠肿瘤模型中评估了联合治疗的疗效。结果：发现抗雄激素药物比卡鲁胺与¹⁸ F-FDG 或 X 射线组合具有相似的毒性，表明其作为放射增敏剂对¹⁸ F-FDG 的敏感性。与 AR 阴性 PC3 细胞相比，细胞增殖试验证明了联合比卡鲁胺^-18 F-FDG 在 AR 阳性 22RV1 和 MDA-MB-231 细胞中的选择性毒性。定量 DNA 损伤和细胞周期阻滞分析进一步证实了辐射诱导的细胞损伤，表明比卡鲁胺作为放射增敏剂对¹⁸F-FDG 介导的辐射损伤。在 MDA-MB-231、22RV1 和 PC3 小鼠肿瘤模型中的动物研究表明，与AR 阴性模型相比，AR 阳性模型中比卡鲁胺和^{18 F-FDG 的组合显着减弱了肿瘤生长。}组织病理学检查证实了体外和体内数据，并证实不存在对重要器官的脱靶毒性。结论：这些数据提供的证据表明¹⁸ F-FDG 与作为放射增敏剂的抗雄激素联合使用可作为放射治疗剂用于消融 AR 阳性癌症。