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

Silvano Gnesin; Nicolas Chouin; Michel Cherel; Steven Mark Dunn; Niklaus Schaefer; Alain Faivre-Chauvet; John O Prior; Judith Anna Delage

doi:10.1186/s13550-023-01010-4

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

EJNMMI Res. 2023 Jun 14;13(1):59. doi: 10.1186/s13550-023-01010-4.

Authors

Silvano Gnesin¹, Nicolas Chouin², Michel Cherel³, Steven Mark Dunn⁴, Niklaus Schaefer⁵, Alain Faivre-Chauvet³, John O Prior⁶, Judith Anna Delage⁷

Affiliations

¹ Institute of Radiation Physics, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland.
² Inserm, CNRS, University of Angers, Oniris, CRCI2NA, University of Nantes, Nantes, France.
³ CHU Nantes, CNRS, Inserm, CRCINA, University of Nantes, 44000, Nantes, France.
⁴ LAbCore, Ludwig Institute for Cancer Research, Lausanne University Hospital and University of Lausanne, 1066, Epalinges, Switzerland.
⁵ Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
⁶ Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland. John.Prior@chuv.ch.
⁷ Radiopharmacy Unit, Department of Pharmacy, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland.

Abstract

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.

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

Abstract

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