From bench to bedside: 64Cu/177Lu 1C1m-Fc anti TEM-1: mice-to-human dosimetry extrapolations for future theranostic applications

EJNMMI Research

Original Research

Michel Cherel¹  Alain Faivre-Chauvet¹  Niklaus Schaefer²  John O. Prior²  Nicolas Chouin³  Silvano Gnesin⁴  Steven Mark Dunn⁵  Judith Anna Delage⁶ 

[1] CHU Nantes, CNRS, Inserm, CRCINA, University of Nantes, 44000, Nantes, France;Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland;Inserm, CNRS, University of Angers, Oniris, CRCI2NA, University of Nantes, Nantes, France;Institute of Radiation Physics, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland;LAbCore, Ludwig Institute for Cancer Research, Lausanne University Hospital and University of Lausanne, 1066, Epalinges, Switzerland;Radiopharmacy Unit, Department of Pharmacy, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland;

关键词: Theranostic;    Fusion protein antibody;    Tumor endothelial marker 1;    Copper-64;    Lutetium-177;    PET imaging;    Radioimmunotherapy;    Dosimetry;    Dose extrapolation;    Clinical translation;   

DOI  :  10.1186/s13550-023-01010-4

 received in 2023-04-24, accepted in 2023-06-06,  发布年份 2023

来源: Springer

【 摘 要 】

The development of diagnostic and therapeutic radiopharmaceuticals is an hot topic in nuclear medicine. Several radiolabeled antibodies are under development necessitating both biokinetic and dosimetry extrapolations for effective human translation. The validation of different animal-to-human dosimetry extrapolation methods still is an open issue. This study reports the mice-to-human dosimetry extrapolation of 64Cu/177Lu 1C1m-Fc anti-TEM-1 for theranostic application in soft-tissue sarcomas. We adopt four methods; direct mice-to-human extrapolation (M1); dosimetry extrapolation considering a relative mass scaling factor (M2), application of a metabolic scaling factor (M3) and combination of M2 and M3 (M4). Predicted in-human dosimetry for the [64Cu]Cu-1C1m-Fc resulted in an effective dose of 0.05 mSv/MBq. Absorbed dose (AD) extrapolation for the [177Lu]Lu-1C1m-Fc indicated that the AD of 2 Gy and 4 Gy to the red-marrow and total-body can be reached with 5–10 GBq and 25–30 GBq of therapeutic activity administration respectively depending on applied dosimetry method. Dosimetry extrapolation methods provided significantly different absorbed doses in organs. Dosimetry properties for the [64Cu]Cu-1C1m-Fc are suitable for a diagnostic in-human use. The therapeutic application of [177Lu]Lu-1C1m-Fc presents challenges and would benefit from further assessments in animals’ models such as dogs before moving into the clinic.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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Fig. 4