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

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.

Promising Application of D-Amino Acids toward Clinical Therapy

“…Furthermore, D-AAs derived positron emission tomography (PET) radiotracers have demonstrated promising application in clinical diagnosis, including brain tumor, brain glioma tissue, and bacterial infection, etc. [157][158][159]. It has better specificity and absorption in tumor/infected tissue, as well as outperforming its L enantiomers [157][158][159].…”

“…[157][158][159]. It has better specificity and absorption in tumor/infected tissue, as well as outperforming its L enantiomers [157][158][159].…”

Recent Advances in 18F-Labeled Amino Acids Synthesis and Application

“…In another study, Tang and coworkers further explored the potential application of [ 18 F] 17 in evaluating glioma by comparing magnetic resonance imaging (MRI) and histopathology. The results showed that, compared with [ 18 F]FDG and [ 18 F] 1 , [ 18 F] 17 had the highest TNRs in the same orthotopic C6 glioma models, suggesting that the tracer may serve as a valuable tool in the diagnosis of gliomas [ 59 ].…”

Synthesis of Secondary Trifluoromethyl Boronic Esters through Visible Light Induced Decarboxylative Alkylation Reactions

“…As displayed in Table 2, for cyclic substrates, both secondary and tertiary alkyl groups, including cycloheptyl (4), various cyclohexyls (5-7), cyclopropyls (8)(9)(10)(11), adamantly (12) all underwent the reaction system smoothly to afford the coupling products in good to excellent yields. Of them, keto (7), -MeO (9), -Cl (10), -CF 2 (11), substituents were all well tolerated, as well as substrates derived from piperidine, tetrahydropyranyl and tetrahydrofuranyl (13)(14)(15). Moreover, no obvious bias toward reaction efficiency was observed in acyclic substrates which exhibited in either secondary (16, 17), primary (18,19) or benzyl (20) structures.…”

“…For instance, 18 F-trifluoroborate-derived tyrosine ( 18 F-FBY) has demonstrated exciting potential in clinical PET imaging. [9][10] Furthermore, both trifluoromethyl and boronic groups have been proved to be valuable functionalities in cold pharmaceuticals, [11][12] as well as in hot radiopharmaceuticals [13][14] (Figure 1a, 1 b). Interestingly, although "F&B couple" hold great promise in PET-BNCT radiotheranostics, efforts to fuse a CF 3 functionality into a boronic molecule to get fluorinated organoboronates were less devoted.…”