¹⁸F-FSPG PET imaging for the evaluation of indeterminate pulmonary nodules

Background: ¹⁸F-fluorodeoxyglucose (FDG) PET/CT is recommended for evaluation of intermediate-risk indeterminate pulmonary nodules (IPNs). While highly sensitive, the specificity of FDG remains suboptimal for differentiating malignant from benign nodules, particularly in areas where fungal lung diseases are prevalent. Thus, a cancer-specific imaging probe is greatly needed. In this study, we tested the hypothesis that a PET radiotracer (S)-4-(3-[¹⁸F]-fluoropropyl)- L-glutamic acid (FSPG) improves the diagnostic accuracy of IPNs compared to ¹⁸FFDG PET/CT. Methods: This study was conducted at a major academic medical center and an affiliated VA medical center. Twenty-six patients with newly discovered IPNs 7-30mm diameter or newly diagnosed lung cancer completed serial PET/CT scans utilizing ¹⁸F-FDG and ¹⁸F-FSPG, without intervening treatment of the lesion. The scans were independently reviewed by two dualtrained diagnostic radiology and nuclear medicine physicians. Characteristics evaluated included quantitative SUVmax values of the pulmonary nodules and metastases. Results: A total of 17 out of 26 patients had cancer and 9 had benign lesions. ¹⁸F-FSPG was negative in 6 of 9 benign lesions compared to 7 of 9 with ¹⁸F-FDG. ¹⁸F-FSPG and ¹⁸F-FDG were positive in 14 of 17 and 12 of 17 malignant lesions, respectively. ¹⁸F-FSPG detected brain and intracardiac metastases missed by ¹⁸F-FDG PET in one case, while ¹⁸F-FDG detected a metastasis to the kidney missed by ¹⁸F-FSPG. Conclusion: In this pilot study, there was no significant difference in overall diagnostic accuracy between ¹⁸F-FSPG and ¹⁸F-FDG for the evaluation of IPNs and staging of lung cancer. Additional studies will be needed to determine the clinical utility of this tracer in the management of IPNs and lung cancer.