Preclinical and First‑in‑human Evaluation of [Ga]Ga-DOTA-PEG-Asp-PDL1P PET Imaging to Assess Tumor PD-L1 Expression

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2025 Mar 3

PMID 40029371

Authors

Yang Chen

Yinting Hu

Ao Li

Guojin Zhang

Danyi Guo

Xinchao Yao

Baozhen Zeng

Ganghua Tang

Benyuan Jiang

Lei Jiang

Affiliations

Soon will be listed here.

Abstract

Purpose: PD-L1 PET imaging can provide a non-invasively and real-time assessment of PD-L1 expression status at tumor sites. This study aimed to evaluate the targeting efficacy and biodistribution of a novel peptide-based PD-L1 PET agent, [Ga]Ga-DOTA-PEG-Asp-PDL1P, in preclinical studies and human participants.

Methods: [Ga]Ga-DOTA-PEG-Asp-PDL1P was synthesized and the probe stability was analyzed in vitro and in vivo. Cellular uptake of the probe was evaluated using tumor cell lines with different PD-L1 expression levels. Small animal PET imaging and semi-quantitative studies were conducted in PC3, H1975 and A549 tumor-bearing mice models, with tumor PD-L1 expression confirmed through immunofluorescence and immunohistochemistry. Furthermore, [Ga]Ga-DOTA-PEG-Asp-PDL1P PET imaging was performed in 1 healthy volunteer and 14 lung cancer patients to assess biodistribution and PD-L1 expression at tumor sites.

Results: [Ga]Ga-DOTA-PEG-Asp-PDL1P exhibited a radiochemical purity of > 99% and had good stability both in vitro and in vivo. In vitro cellular uptake and in vivo small animal PET imaging revealed the probe binding to PD-L1 with high affinity and specificity, consistent with the results of immunofluorescence and immunohistochemistry. In the clinical study involving 15 participants, [Ga]Ga-DOTA-PEG-Asp-PDL1P was proven safe with demonstrating low uptake in normal organs and physiologically excreting via the urinary system. Lung cancer patients with high PD-L1 expression (TPS 70-90%) exhibited higher tumor uptake and tumor-to-background ratios than those with negative or low PD-L1 expression (TPS < 1-10%), with SUVmax of 1.89-2.27 vs. 0.87-1.01, tumor-to-lung ratios of 4.73-7.68 vs. 1.61-2.35, and tumor-to-muscle ratios of 6.73-12.61 vs. 4.35-5.61.

Conclusion: [Ga]Ga-DOTA-PEG-Asp-PDL1P showed promising as a PET agent to assess tumor PD-L1 expression in preclinical and first-in-human studies, offering a non-invasive, real-time and accurate tool to address clinical challenges in predicting and assessing the efficacy of immunotherapy.

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