Effect of molar dose on the in vivo tissue biodistribution profile of FAP-targeted radioligand therapeutics.

Autor: Galbiati A; R&D Department, Philochem AG, CH-8112, Otelfingen, Switzerland. andrea.galbiati@philochem.ch., Bocci M; R&D Department, Philochem AG, CH-8112, Otelfingen, Switzerland., Neri D; Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, CH-8093, Zurich, Switzerland.; Philogen S.p.A., I-53100, Siena, Italy., Cazzamalli S; R&D Department, Philochem AG, CH-8112, Otelfingen, Switzerland. samuele.cazzamalli@philochem.ch.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2024 Nov 12. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1007/s00259-024-06969-3
Abstrakt: Purpose: 177 Lu-OncoFAP-23 is a novel FAP-targeted radioligand therapeutic (RLT) with high and prolonged tumor residence time and promising preclinical efficacy. In this work, we investigated the correlation between the injected molar dose and the in vivo tumor-to-organ ratios and tumor-targeting performance of 177 Lu-OncoFAP-23.
Methods: We evaluated the quantitative biodistribution profile of 177 Lu-OncoFAP-23 at different molar doses (i.e., 3 to 2250 nmol/kg) in tumor-bearing mice by means of ex vivo gamma counting, we included 177 Lu-OncoFAP and 177 Lu-BiOncoFAP as experimental controls.
Results: The biodistribution profile of 177 Lu-OncoFAP-23 strongly depends on the molar dose injected. Molar doses below 30 nmol/kg result in unwanted uptake of the compound in healthy organs, while doses higher than 725 nmol/kg determined a reduced tumor uptake due to receptor saturation. We identified an optimal molar dose ranging from 90 to 250 nmol/kg, characterized by elevated tumor uptake and adequate tumor-to-organ ratios.
Conclusion: 177 Lu-OncoFAP-23 presents a favorable in vivo biodistribution profile at molar doses ranging from 90 to 250 nmol/kg in tumor-bearing mice. Our results guide the design of the first-in-human Phase I clinical trial with this novel FAP-targeted radioligand therapeutic.
Competing Interests: Declarations Competing interests DN is co-founder, CEO, CSO, and President of the Scientific Advisory Board of Philogen. AG, MB and SC are employed by Philochem AG, the research and development unit of the Philogen group.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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