Evaluation of D-isomer of 18F-FBPA for oncology PET focusing on the differentiation of glioma and inflammation
نویسندگان
1 Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
2 Institute for Radiation Sciences, Osaka University, Osaka, Japan
3 Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
4 Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
5 Deparment of Radiology, Osaka University Hospital, Immunology Frontier Research Center, Osaka University, Osaka, Japan
6 Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
7 Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
8 Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
9 Laboratory of Biomolecular Dynamics, Department of Collaborative Research, Nara Medical University, Nara, Japan
10 Laboratory of Biomolecular Dynamics, Department of Collaborative Research, Nara Medical University, Nara, Japan
11 Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
12 Laboratory of Biomolecular Dynamics, Department of Collaborative Research, Nara Medical University, Nara, Japan
13 Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
14 Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
15 Deparment of Radiology, Osaka University Hospital, Immunology Frontier Research Center, Osaka University, Osaka, Japan
doi
10.22038/aojnmb.2020.47399.1321چکیده
Objective(s): L-4-borono-2-18F-fluoro-phenylalanine (L-[18F]FBPA), a substrate of L-type amino acid transporter 1 (LAT1), is a tumor-specific probe used in positron emission tomography (PET). On the other hand, it has not been examined whether another isomer D-[18F]FBPA accumulates specifically in the tumor. Here, we compared the accumulation of D-[18F]FBPA in C6 glioma and inflammation to evaluate the performance of D-[18F]FBPA as a tumor-specific probe. Methods: HEK293-LAT1 and HEK293-LAT2 cells were tested for [14C]-leucine or [14C]-alanine transport, and IC50 values of L- and D-FBPA were evaluated in both cell types. PET was conducted in rat xenograft model of C6 glioma with LAT1 expression and model of turpentine oil-induced subcutaneous inflammation (n=10 for both models). The concentrations of D-[18F]FBPA were compared between glioma and inflammatory lesion using standardized uptake value (SUV). Results: In contrast to L-FBPA, which inhibited substrate uptake in both HEK293-LAT1 and -LAT2 cells, D-FBPA showed no inhibitory effect on both cells, suggesting low transporter selectivity of D-[18F]FBPA against LAT1 and LAT2. Static PET analysis showed low accumulation of D-[18F]FBPA in C6 glioma and inflammatory lesion (SUVmax=0.80±0.16, 0.56±0.09, respectively). Although there was a statistical difference in SUVmax between these tissues, it was difficult to distinguish glioma from inflammation on the PET image due to its low uptake level. Therefore, it was suggested that D-[18F]FBPA is not a suitable tumor-specific probe for oncology PET in contrast to L-[18F]FBPA. Conclusion: This study demonstrated that D-[18F]FBPA is not a LAT1-specific PET probe and shows low uptake in C6 glioma, indicating its unsuitability as a tumor diagnosis PET probe.
