Bioequivalence and Dosimetry Estimates of GD2-Targeting Dinutuximab-Beta Labeled with In-111, Lu-177, and Ac-225

Evaluating translational dosimetry strategies for GD2-targeted radiopharmaceutical therapy in neuroblastoma using beta- and alpha-emitting radionuclides.

Authors: Filipa Mota, Peter Gawne, Sandy Chu, Jack Heimann, Ahuva Friedman, Harmony Blythin, Keryn Gresco, Jane K. Sosabowski

Dinutuximab-Beta (DB), a monoclonal antibody targeting GD2, is currently approved for the treatment of high-risk neuroblastoma and is being investigated as a potential vector for molecular radiotherapy. In this study, researchers evaluated the biodistribution and dosimetry profiles of DB labeled with In-111, Lu-177, and Ac-225 to assess translational imaging potential and projected human dosimetry.

The work demonstrated comparable biodistribution profiles across the three radiolabeled compounds, while also identifying important considerations related to Ac-225 bone accumulation and dose-limiting organ exposure. Additionally, the study explored the use of In-111 as a surrogate imaging isotope for dosimetry estimation of therapeutic radionuclides, highlighting both the potential and limitations of bioequivalence assumptions in translational radiopharmaceutical development.

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• How In-111 may serve as a surrogate imaging isotope for Lu-177 and Ac-225 dosimetry workflows
• Key biodistribution and toxicity considerations for GD2-targeted radiopharmaceutical therapy development
• Human dosimetry projection strategies supporting translational neuroblastoma RLT programs