{"doi":"10.2967/jnumed.121.262958","title":"Antiandrogen Therapy Radiosensitizes Androgen Receptor–Positive Cancers to <sup>18</sup>F-FDG","abstract":"<b>Background:</b> A subset (35%) of triple negative breast cancers (TNBC) express androgen receptor (AR) activity. However, clinical trials with anti-androgen drugs have shown limited efficacy with about a 19% clinical benefit rate. We investigate the therapeutic enhancement of anti-androgens as radiosensitizers in combination with <sup>18</sup>F-fluoro-2-deoxy-D-glucose (<sup>18</sup>F-FDG) in TNBC. <b>Methods:</b> We screened five candidate drugs to evaluate shared toxicity when combined with either <sup>18</sup>F-FDG, X-ray or ultraviolet (UV) radiation, at doses below their respective sub-IC50 values. Cytotoxic enhancement of anti-androgen in combination with <sup>18</sup>F-FDG was evaluated using cell proliferation and DNA damage assays. Finally, therapeutic efficacy of the combination treatment was evaluated in mouse tumor models of TNBC and prostate cancer. <b>Results:</b> Bicalutamide (Bical), an anti-androgen drug, was identified to share similar toxicity in combination with either <sup>18</sup>F-FDG or X-rays, indicating its sensitivity as a radiosensitizer to <sup>18</sup>F-FDG. Cell proliferation assays demonstrated selective toxicity of combination Bical-<sup>18</sup>F-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 Bical as a radiosensitizer to <sup>18</sup>F-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 Bical and <sup>18</sup>F-FDG in the AR-positive model in comparison to the AR-negative model. Histopathology corroborated the in vitro and in vivo data and confirmed the absence of off-target toxicity to vital organs. <b>Conclusion:</b> These data provide evidence that <sup>18</sup>F-FDG in conjunction with anti-androgens serving as radiosensitizers has utility as a radiotherapeutic agent in the ablation of AR-positive cancers.","journal":"Journal of Nuclear Medicine","year":2021,"id":195178,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":765901,"name":"Henry B. Spitz","orcid":"0000-0002-9568-9693","position":1,"is_corresponding":false},{"id":405112,"name":"Mary C. Mahoney","orcid":"0000-0001-6139-9201","position":2,"is_corresponding":false},{"id":762945,"name":"Zhongyun Dong","orcid":"0000-0003-3906-301X","position":3,"is_corresponding":false},{"id":523580,"name":"Nalinikanth Kotagiri","orcid":"0000-0003-0066-4563","position":4,"is_corresponding":false},{"id":765900,"name":"Indulekha Singaravelu","orcid":"0000-0003-2531-8632","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T23:50:03.719152Z","pmid":"34772792","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}