Development of PD-L1 Targeting Small-Molecule Immunotheranostic Agents for Personalized Antitumor Immunotherapy

Immune checkpoint blockade targeting PD-1/PD-L1 has transformed
cancer treatment but faces challenges such as low response rates and
a lack of reliable biomarkers. To address these issues, we developed
a novel small-molecule immunotheranostic agent, [18F]LG-8,
and its therapeutic counterpart LG-8, which share identical structures
to ensure consistent biodistribution. [18F]LG-8 PET specifically
quantified PD-L1 in murine melanoma (B16–F10) and lung carcinoma
(LLC) models. LG-8 exhibited potent antitumor efficacy in B16–F10
tumors with high PD-L1 uptake but not in LLC models with low PD-L1
expression, confirming the predictive value of the diagnostic scan.
Furthermore, we implemented an individualized chemo-immunotherapy
strategy guided by [18F]LG-8 PET imaging, where cisplatin
pretreatment enhanced PD-L1 expression in a subset of LLC tumors,
enabling effective LG-8 treatment only in mice with elevated PD-L1
levels. This theranostic approach integrates precise diagnosis and
immunotherapy within a unified molecular platform, significantly improving
response prediction and advancing personalized cancer immunotherapy.