![]() Kratochwil C, Bruchertseifer F, Giesel FL, Weis M, Verburg FA, Mottaghy F, et al. ![]() Broadening horizons with 225Ac-DOTATATE targeted alpha therapy for gastroenteropancreatic neuroendocrine tumour patients stable or refractory to 177Lu-DOTATATE PRRT: first clinical experience on the efficacy and safety. Cellular and genetic determinants of the sensitivity of cancer to alpha-particle irradiation. Yard BD, Gopal P, Bannik K, Siemeister G, Hagemann UB, Abazeed ME. Mechanisms of resistance to high and low linear energy transfer radiation in myeloid leukemia cells. Global comparison of targeted alpha vs targeted beta therapy for cancer: in vitro, in vivo and clinical trials. Sublethal exposure to alpha radiation ( 223Ra dichloride) enhances various carcinomas’ sensitivity to lysis by antigen-specific cytotoxic T lymphocytes through calreticulin-mediated immunogenic modulation. Malamas AS, Gameiro SR, Knudson KM, Hodge JW. Basic mechanisms of therapeutic resistance to radiation and chemotherapy in lung cancer. Willers H, Azzoli CG, Santivasi WL, Xia F. ![]() Clustered damages and total lesions induced in DNA by ionizing radiation: oxidized bases and strand breaks. Sutherland BM, Bennett PV, Sidorkina O, Laval J. Initial events in the cellular effects of ionizing radiations: clustered damage in DNA. Molecular pathways: targeted alpha-particle radiation therapy. 2019 4:27.īaidoo KE, Yong K, Brechbiel MW. Auger electrons for cancer therapy - a review. Survival and DNA damage in Chinese hamster V79 cells exposed to alpha particles emitted by DNA-incorporated astatine-211. Walicka MA, Vaidyanathan G, Zalutsky MR, Adelstein SJ, Kassis AI. Advances in radiotherapy and implications for the next century: a historical perspective. Biological response of cancer cells to radiation treatment. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fossa SD, et al. Efficacy and safety of high-specific-activity 131I-MIBG therapy in patients with advanced pheochromocytoma or paraganglioma. Pryma DA, Chin BB, Noto RB, Dillon JS, Perkins S, Solnes L, et al. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. ©2022 The Authors Published by the American Association for Cancer Research.Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. An alpha particle emitting radiopharmaceutical may be effective against microscopic disseminated disease, warranting clinical development. MABG has significant survival advantage in disseminated models of neuroblastoma. Survival was significantly prolonged for mice treated with 12.9 MBq/kg/fraction (0.35 mCi/kg) × 4 doses over 11 days MABG in the disseminated disease (IMR-05NET/GFP/LUC) model (P = 0.003) suggesting eradication of microscopic disease. Both 66.7 MBq/kg (1.8 mCi/kg) single dose and fractionated dosing 16.6 MBq/kg/fraction (0.45 mCi/kg) × 4 over 11 days induced marked tumor regression in two of the three models studied. Long-term toxicity studies on mice administered with doses up to 41.5 MBq/kg (1.12 mCi/kg) showed the radiotherapeutic to be well tolerated. Biodistribution of MABG was similar to MIBG. The MTD of MABG was 66.7 MBq/kg (1.8 mCi/kg) in CB17SC scid-/- mice and 51.8 MBq/kg (1.4 mCi/kg) in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Finally, we explored the efficacy of MABG after tail vein xenografting designed to model disseminated neuroblastoma. We compared the antitumor efficacy of MABG with MIBG in three murine xenograft models. We defined the maximum tolerated dose (MTD), biodistribution, and toxicity of MABG in immunodeficient mice in comparison with MIBG. Here we investigated the safety and antitumor activity MABG in preclinical models of neuroblastoma. meta-astatobenzylguanidine ( MABG) is an alpha particle emitter with higher biological effectiveness and short path length which effectively sterilizes microscopic residual disease. However, relapses in the bone marrow are common. Meta-iodobenzylguanidine (MIBG) is a targeted radiotherapeutic administered systemically to deliver beta particle radiation in neuroblastoma.
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