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

• Main Authors: Nobuto Hirai, Tadashi Watabe, Shushi Nagamori, Pattama Wiriyasermkul, Yoko Tanaka, Victor Romanov, Sadahiro Naka, Yasukazu Kanai, Yuwei Liu, Naoki Tani, Tatsuya Sakai, Mitsuaki Tatsumi, Eku Shimosegawa, Yoshikatsu Kanai, Jun Hatazawa
• Format: Article
• Language: English
• Published: Mashhad University of Medical Sciences 2020-07-01
• Series: Asia Oceania Journal of Nuclear Medicine and Biology
• Subjects: fbpa; small animal pet; lat1; c6 glioma; inflammation
• Online Access: http://aojnmb.mums.ac.ir/article_15933_dacd8d3c15f596d6ced75e02b3188e1a.pdf

<strong><em><strong><em>Objective(s):</em></strong> </em></strong>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.<br /> <strong><em>Methods:</em></strong> 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).<br /> <strong><em>Results:</em></strong> 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 (SUV_max=0.80±0.16, 0.56±0.09, respectively). Although there was a statistical difference in SUV_max 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.<br /> <strong><em>Conclusion:</em></strong> 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.