Abstract
Comparing MRI and histopathology, this study aims to comprehensively explore the potential application of 18F-trifluoromethylated D-cysteine (S-[18F]CF3-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)], [18F]FDG, S-[18F]CF3-D-CYS, and [18F]FDOPA PET imaging. Repeated scans of the same rat with the two or three [18F]-labeled radiotracers were investigated. Initial regions of interest were manually delineated on T2WI 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-[18F]CF3-D-CYS and Ki67 were analyzed. Dynamic S-[18F]CF3-D-CYS PET imaging showed tumor uptake rapidly reached a peak, maintained plateau during 10–30 min after injection, then decreased slowly. Compared with [18F]FDG and [18F]FDOPA PET imaging, S-[18F]CF3-D-CYS PET demonstrated the highest TNRs (P < 0.05). There were no significant differences in the tumor volume measured on S-[18F]CF3-D-CYS PET or HE specimen. Furthermore, our results showed that the uptake of S-[18F]CF3-D-CYS was significantly positively correlated with tumor Ki67, and the poor accumulated S-[18F]CF3-D-CYS was consistent with tumor hemorrhage. There was no significant correlation between the S-[18F]CF3-D-CYS uptakes and the Ktrans values derived from DCE-MRI. In comparison with MRI and histopathology, S-[18F]CF3-D-CYS PET performs well in the diagnosis and evaluation of glioma. S-[18F]CF3-D-CYS PET may serve as a valuable tool in the clinical management of gliomas.
Highlights
Gliomas are the most common primary intracranial tumor with high mortality and poor prognosis
The dynamic TNR curve revealed that the mean TNRs of S[18F]CF3-D-CYS were constant from 10 to 30 min p.i., which indicated that the optimal acquisition time for static PET imaging was at 10–30 min after injections
Compared with [18F]FDG and [18F]FDOPA PET imaging, S[18F]CF3-D-CYS PET imaging had the highest TNRs, which was an advantage for tumor boundary delineation
Summary
Gliomas are the most common primary intracranial tumor with high mortality and poor prognosis. The high tumor heterogeneity and invasiveness present a considerable obstacle to the treatment of glioma, which was the reason for causing tumor recurrence and treatment resistance [1]. Seeking a non-invasive modality to the full extent of depicting the tumor invasion and demonstrating the tumor heterogeneity is proficient for glioma diagnosis and treatment design. MRI has been routinely and wildly used to evaluate gliomas. The conventional and advanced MRI sequences are still not good enough to identify the tumor boundary and to provide all needed pathophysiological information of gliomas [2, 3]. Beyond the MRI, PET provides additional insights into the pathophysiology of gliomas [4, 5]
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