Evaluation of D-isomer of 18F-FBPA for oncology PET focusing on the differentiation of glioma and inflammation

Document Type: Original Article

Authors

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 Laboratory of Biomolecular Dynamics, Department of Collaborative Research, Nara Medical University, Nara, Japan

5 Deparment of Radiology, Osaka University Hospital, Immunology Frontier Research Center, Osaka University, Osaka, Japan

6 Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan

7 Research Center for Nuclear Physics, Osaka University, Osaka, Japan

Abstract

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.

Keywords


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