(18)F-Trifluoromethylated D-Cysteine as a Promising New PET Tracer for Glioma Imaging: Comparative Analysis With MRI and Histopathology in Orthotopic C6 Models

Comparing MRI and histopathology, this study aims to comprehensively explore the potential application of (18)F-trifluoromethylated D-cysteine (S-[(18)F]CF(3)-D-CYS) in evaluating glioma by using orthotopic C6 glioma models. Sprague–Dawley (SD) rats (n = 9) were implanted with C6 glioma cells. Tumor growth was monitored every week by multiparameter MRI [including dynamic contrast-enhanced MRI (DCE-MRI)], [(18)F]FDG, S-[(18)F]CF(3)-D-CYS, and [(18)F]FDOPA PET imaging. Repeated scans of the same rat with the two or three [(18)F]-labeled radiotracers were investigated. Initial regions of interest were manually delineated on T(2)WI and set on the same level of PET images, and tumor-to-normal brain uptake ratios (TNRs) were calculated to semiquantitatively assess the tracer accumulation in the tumor. The tumor volume in PET and histopathology was calculated. HE and Ki67 immunohistochemical staining were further performed. The correlations between the uptake of S-[(18)F]CF(3)-D-CYS and Ki67 were analyzed. Dynamic S-[(18)F]CF(3)-D-CYS PET imaging showed tumor uptake rapidly reached a peak, maintained plateau during 10–30 min after injection, then decreased slowly. Compared with [(18)F]FDG and [(18)F]FDOPA PET imaging, S-[(18)F]CF(3)-D-CYS PET demonstrated the highest TNRs (P < 0.05). There were no significant differences in the tumor volume measured on S-[(18)F]CF(3)-D-CYS PET or HE specimen. Furthermore, our results showed that the uptake of S-[(18)F]CF(3)-D-CYS was significantly positively correlated with tumor Ki67, and the poor accumulated S-[(18)F]CF(3)-D-CYS was consistent with tumor hemorrhage. There was no significant correlation between the S-[(18)F]CF(3)-D-CYS uptakes and the K(trans) values derived from DCE-MRI. In comparison with MRI and histopathology, S-[(18)F]CF(3)-D-CYS PET performs well in the diagnosis and evaluation of glioma. S-[(18)F]CF(3)-D-CYS PET may serve as a valuable tool in the clinical management of gliomas.