Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2

Objective L-type amino acid transporter 1 (LAT1) is strongly expressed on the cell membrane in various types of human cancer cells, while being minimally expressed in normal or inflammatory tissues. Therefore, LAT1-targeting PET tracers have been developed for cancer-specific imaging. The purpose of this study was to study the distribution of two LAT1-targeting PET tracers, L-4-borono-2- 18 F-fluoro-phenylalanine ( 18 F-FBPA) and L-3- 18 F-alpha-methyl tyrosine ( 18 F-FAMT), in relation to the tumor blood flow, using rat xenograft models. Methods Rat tumor xenograft models of C6 glioma ( n = 4; tumors = 8) and MIA PaCa-2 (pancreatic cancer) ( n = 4; tumors = 6) were used. The expressions of LAT1 and CD98hc were evaluated by both immunofluorescence staining and western blot analysis. Dynamic PET was performed after injection of 18 F-FAMT or 18 F-FBPA (scan duration = 70 min) following 15 O-water PET (scan duration = 10 min). The PET data were subjected to kinetic analyses, and the K 1 , k 2 , and total distribution volume ( V t ) were calculated using the one-tissue compartment model. The accumulation of the LAT1 tracers was expressed in terms of their V t . Tumor blood flow (TBF) was represented by the K 1 value in 15 O-water PET. Results LAT1/CD98hc expression was confirmed in both xenografts by immunofluorescence staining. Western blot analysis showed higher functional expression of LAT1 in the C6 glioma cells as compared to the MIA PaCa-2 cells (C6 glioma/MIA PaCa-2 relative expression ratio = 1.70). The V t values of both 18 F-FBPA and 18 F-FAMT were significantly higher in the C6 glioma xenografts than in the MIA PaCa-2 xenografts (C6 glioma: 2.27 ± 0.35 and 2.03 ± 0.23, respectively; MIA PaCa-2: 1.28 ± 0.26 and 1.35 ± 0.15, respectively). Meanwhile, there was no significant correlation of the V t value of either 18 F-FBPA or 18 F-FAMT with the TBF, in either the C6 glioma or the MIA PaCa-2 xenografts. Conclusions This study revealed that total distribution volumes of the LAT1-targeting PET tracers 18 F-FBPA and 18 F-FAMT were independent of the tumor blood flow and might reflect the functional expression levels of LAT1 in the C6 glioma and MIA PaCa-2 xenograft models.