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• W2149549005 abstract "Abstract Purpose: Previous experience in solid tumor radioimmunotherapy studies has indicated that greatest therapeutic efficacy is achieved in the treatment of small-volume disease. α-Particle–emitting radioisotopes possess several physical characteristics ideally suited to the treatment of minimal residual disease. Therefore, we have investigated the efficacy of the α-particle–emitting bismuth-213 (213Bi) radioimmunotherapy using the humanized anti-Lewis Y (Ley) monoclonal antibody humanized 3S193 (hu3S193). Experimental Design: The intracellular localization of hu3S193 in Ley-positive MCF-7 breast carcinoma cells was assessed by confocal microscopy. Cytotoxicity of 213Bi-hu3S193 and apoptosis was assessed using [3H]thymidine incorporation assay and ELISA, respectively. Immunoblotting for γ-H2AX assessed DNA strand breaks. In vivo efficacy of 213Bi-hu3S193 was assessed using a minimal residual disease model in BALB/c nude mice, with radioconjugate [15, 30, and 60 μCi (9.2 μg)] injected 2 days after s.c. implantation of MCF-7 cells. Radioimmunotherapy was also combined with a single injection of 300 μg paclitaxel to explore improved efficacy. Further, mice with established tumors received 30, 60, or 120 μCi (14.5 μg) of 213Bi-hu3S193 to assess the effect of tumor volume on treatment efficacy. Results: hu3S193 is internalized via an endosomal and lysosomal trafficking pathway. Treatment with 213Bi-hu3S193 results in &gt;90% cytotoxicity in vitro and induces apoptosis and increased γ-H2AX expression. 213Bi-hu3S193 causes specific and significant retardation of tumor growth even in established tumors, and efficacy was enhanced by paclitaxel to produce defined complete responses. Conclusions: These studies show the potency of α-particle radioimmunotherapy and warrant its further exploration in the treatment of micrometastatic disease in Ley-positive malignancies." @default.
• W2149549005 created "2016-06-24" @default.
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• W2149549005 date "2007-09-15" @default.
• W2149549005 modified "2023-10-18" @default.
• W2149549005 title "Radioimmunotherapy with α-Particle–Emitting 213Bi-C-Functionalized <i>trans</i>-Cyclohexyl-Diethylenetriaminepentaacetic Acid-Humanized 3S193 Is Enhanced by Combination with Paclitaxel Chemotherapy" @default.
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• W2149549005 doi "https://doi.org/10.1158/1078-0432.ccr-07-1071" @default.
• W2149549005 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17875796" @default.
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