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

Abstract

¹⁷⁷Lu-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 ¹⁷⁷Lu-OncoFAP-23. We evaluated the quantitative biodistribution profile of ¹⁷⁷Lu-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 ¹⁷⁷Lu-OncoFAP and ¹⁷⁷Lu-BiOncoFAP as experimental controls. The biodistribution profile of ¹⁷⁷Lu-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. ¹⁷⁷Lu-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.