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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_91574209E2BB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
From bench to bedside: 64Cu/177Lu 1C1m-Fc anti TEM-1: mice-to-human dosimetry extrapolations for future theranostic applications.
Journal
EJNMMI research
Author(s)
Gnesin S., Chouin N., Cherel M., Dunn S.M., Schaefer N., Faivre-Chauvet A., Prior J.O., Delage J.A.
ISSN
2191-219X (Print)
ISSN-L
2191-219X
Publication state
Published
Issued date
14/06/2023
Peer-reviewed
Oui
Volume
13
Number
1
Pages
59
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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 <sup>64</sup> Cu/ <sup>177</sup> Lu 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 [ <sup>64</sup> Cu]Cu-1C1m-Fc resulted in an effective dose of 0.05 mSv/MBq. Absorbed dose (AD) extrapolation for the [ <sup>177</sup> Lu]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 [ <sup>64</sup> Cu]Cu-1C1m-Fc are suitable for a diagnostic in-human use. The therapeutic application of [ <sup>177</sup> Lu]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
Pubmed
Web of science
Open Access
Yes
Create date
15/06/2023 17:40
Last modification date
23/01/2024 8:30
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