evaluation of d-isomer of 18f-fbpa for oncology pet focusing on the differentiation of glioma and inflammation

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.