Increased [¹⁸F]FDG uptake of radiation-induced giant cells: a single-cell study in lung cancer models

Positron emission tomography (PET), a cornerstone in cancer diagnosis and treatment monitoring, relies on the enhanced uptake of fluorodeoxyglucose ([¹⁸F]FDG) by cancer cells to highlight tumors and other malignancies. While instrumental in the clinical setting, the accuracy of [¹⁸F]FDG-PET is susceptible to metabolic changes introduced by radiation therapy. Specifically, radiation induces the formation of giant cells, whose metabolic characteristics and [¹⁸F]FDG uptake patterns are not fully understood. Through a novel single-cell gamma counting methodology, we characterized the [¹⁸F]FDG uptake of giant A549 and H1299 lung cancer cells that were induced by radiation, and found it to be considerably higher than that of their non-giant counterparts. This observation was further validated in tumor-bearing mice, which similarly demonstrated increased [¹⁸F]FDG uptake in radiation-induced giant cells. These findings underscore the metabolic implications of radiation-induced giant cells, as their enhanced [¹⁸F]FDG uptake could potentially obfuscate the interpretation of [¹⁸F]FDG-PET scans in patients who have recently undergone radiation therapy.