FAP-targeted radioligand therapy with ⁶⁸Ga/¹⁷⁷Lu-DOTA-2P(FAPI)₂ enhance immunogenicity and synergize with PD-L1 inhibitors for improved antitumor efficacy.

ABSTRACT:

Background

Fibroblast activation protein (FAP)-targeted radioligand therapy, with immunomodulatory effects, has shown efficacy in both preclinical and clinical studies. We recently reported on a novel dimeric FAP-targeting radiopharmaceutical, ⁶⁸Ga/¹⁷⁷Lu-DOTA-2P(FAPI)₂, which demonstrated increased tumor uptake and prolonged retention in various cancers. However, further exploration is required to understand the therapeutic efficacy and underlying mechanisms of combining ⁶⁸Ga/¹⁷⁷Lu-DOTA-2P(FAPI)₂ radioligand therapy with PD-1/PD-L1 immunotherapy.

Methods

Regarding the change in PD-L1 expression and DNA double-strand breaks induced by radiopharmaceuticals, CT26-FAP tumor cells were incubated with ⁶⁸G

SUBMITTER: Chen J 

PROVIDER: S-EPMC11749305 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature