Evaluation of D-isomer of 18F-FBPA for oncology PET focusing on the differentiation of glioma and inflammation.
Evaluation of D-isomer of 18F-FBPA for oncology PET focusing on the differentiation of glioma and inflammation.
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DOI：
10.22038/aojnmb.2020.47399.1321
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发表时间：
2020-01-01
影响因子：
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通讯作者：
Hatazawa, Jun
中科院分区：
文献类型：
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作者：
Hirai, Nobuto;Watabe, Tadashi;Hatazawa, Jun
目的：L-[18 F]FBPA（L-4-borono-2-18F-fluoro-phenylalanine）是L-型氨基酸转运蛋白1（LAT 1）的底物，是一种肿瘤特异性正电子发射断层扫描（PET）探针。另一方面，尚未检查另一种异构体D-[18 F]FBPA是否在肿瘤中特异性积聚。在这里，我们比较了D-[18 F]FBPA在C6胶质瘤和炎症中的积累，以评估D-[18 F]FBPA作为肿瘤特异性probase.METHODS的性能：HEK 293-LAT 1和HEK 293-LAT 2细胞进行[14 C]-亮氨酸或[14 C]-丙氨酸转运测试，并在两种细胞类型中评估L-和D-FBPA的IC 50值。在具有LAT 1表达的C6胶质瘤的大鼠异种移植模型和松节油诱导的皮下炎症模型中进行PET（两种模型n=10）。结果：与L-FBPA相比，D-FBPA对HEK 293-LAT 1和-LAT 2细胞的底物摄取均具有抑制作用，但对两种细胞均无抑制作用，提示D-FBPA对LAT 1和LAT 2的转运选择性较低。静态PET分析显示D-[18F]FBPA在C6胶质瘤和炎性病变中的低蓄积（SUVmax分别为0.80±0.16，0.56±0.09）。尽管这些组织之间的SUVmax存在统计学差异，但由于其摄取水平低，因此难以在PET图像上区分胶质瘤和炎症。结论：D-[18 F] FBPA不是一种肿瘤特异性PET探针，在C6胶质瘤中的摄取较低，不适合作为肿瘤诊断的PET探针。
OBJECTIVES: 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.