Pilot study of ¹⁸F-FSPG vs¹⁸F-FDG PET imaging for response assessment in cancer

Objectives: ¹⁸F-FDG PET/CT is widely used for therapeutic response assessment in many cancers, although the change can vary greatly depending on the type of treatment (chemotherapy vs. immunotherapy or radiotherapy). ¹⁸F-labeled FSPG, an L-glutamate derivative, has shown to be a promising radiotracer for PET imaging of the amino acid antiporter system xC- that is involved in detoxification processes and balancing oxidative stress. This prospective pilot study is the first to evaluate the utility of ¹⁸F-FSPG PET for response assessment following therapy, in comparison to ¹⁸F-FDG.

Methods: Seven patients were enrolled in this study, including three renal cell cancer (RCC) patients treated with an investigational glutaminase inhibitor and four non-small cell lung cancer (NSCLC) patients treated with external beam radiation therapy. ¹⁸F-FDG and ¹⁸F-FSPG scans were taken within 1 month of each other, once at baseline and again after treatment. Maximum standardized uptake value (SUV) and bidimensional size were measured for up to six of the hottest lesions on each scan.

Results: A variety of treatment responses were seen. Two patients with favorable response to therapy showed similar response on ¹⁸F-FDG and ¹⁸F-FSPG scans. Of two patients who had worsening disease, one showed discordant findings with decreasing ¹⁸F-FDG but increasing ¹⁸F-FSPG uptake, while the other showed progression on both ¹⁸F-FDG and ¹⁸F-FSPG, although more new lesions were identified on the latter. Another patient had stable disease, which was demonstrated as such on ¹⁸F-FDG, but had no uptake with ¹⁸F-FSPG. Two patients have not yet had their post-treatment FSPG scans. Notably, one has multiple known hepatic metastases that were not ¹⁸F-FDG-avid or ¹⁸F-FSPG-avid.

Conclusion: This pilot study shows some similarities as well as discordance in response assessment between ¹⁸F-FDG and ¹⁸F-FSPG likely relative to their alternative mechanisms of uptake. Additional studies are needed to better understand these differences and their clinical utility. Research Support:

• Download figure
• Open in new tab
• Download powerpoint