Galectin expression detected by ⁶⁸Ga-galectracer PET as a predictive biomarker of radiotherapy resistance.

Abstract

Hypoxia is a hallmark of solid tumors that is related to radiotherapy resistance. As galectin members, such as galectin-1 and galectin-3, are associated with tumor hypoxia, herein we aimed to investigate whether positron emission tomography (PET) imaging of galectin expression can be employed to effectively pinpoint tumor hypoxia, and to predict radiotherapy resistance. We synthesized a galectin-targeting radiotracer, designated ⁶⁸Ga-galectracer, by radiolabeling a thiodigalactoside derivative. The properties of ⁶⁸Ga-galectracer for PET imaging of tumor hypoxia were characterized in three tumor hypoxia mouse models. Additionally, preliminary PET/CT was performed in two patients with lung cancer to investigate the potential application of ⁶⁸Ga-galectracer for clinical imaging. High-contrast imaging was achieved in the murine acute hypoxia tumor model, A549 natural hypoxia model, and sorafenib treatment-induced hypoxic 4T1 tumor model by PET using ⁶⁸Ga-galectracer. In fact, ⁶⁸Ga-galectracer exhibited superior hypoxia detection to that of ¹⁸F-misonidazole in the 4T1 tumors. Moreover, tumors with high galectin expression levels, as detected by ⁶⁸Ga-galectracer PET, exhibited significantly lower responses to subsequent radiotherapy compared to those with low galectin expression levels. In patients with lung cancer, PET imaging using ⁶⁸Ga-galectracer provided data that were complementary to that of the glucose metabolic PET radiotracer ¹⁸F-fluorodeoxyglucose. ⁶⁸Ga-galectracer is a promising radiotracer for PET-based imaging of tumor hypoxia in vivo. Thus, hypoxia PET with ⁶⁸Ga-galectracer could provide a noninvasive approach to proactively predict radiotherapy efficacy. Chictr.org.cn (ChiCTR2000029522). Registered 03 February 2020.