論文 - 詳細
| RRC ID | 59683 |
|---|---|
| 著者 | Aoki M, Watabe T, Nagamori S, Naka S, Ikeda H, Kongpracha P, Horitsugi G, Kanai Y, Shimosegawa E, Kanai Y, Hatazawa J. |
| タイトル | Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2. |
| ジャーナル | Ann Nucl Med |
| Abstract |
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-2-18F-fluoro-phenylalanine (18F-FBPA) and L-3-18F-alpha-methyl tyrosine (18F-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 18F-FAMT or 18F-FBPA (scan duration = 70 min) following 15O-water PET (scan duration = 10 min). The PET data were subjected to kinetic analyses, and the K1, k2, and total distribution volume (Vt) were calculated using the one-tissue compartment model. The accumulation of the LAT1 tracers was expressed in terms of their Vt. Tumor blood flow (TBF) was represented by the K1 value in 15O-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 Vt values of both 18F-FBPA and 18F-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 Vt value of either 18F-FBPA or 18F-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 18F-FBPA and 18F-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. |
| 巻・号 | 33(6) |
| ページ | 394-403 |
| 公開日 | 2019-6-1 |
| DOI | 10.1007/s12149-019-01346-9 |
| PII | 10.1007/s12149-019-01346-9 |
| PMID | 30820863 |
| MeSH | Animals Blood Circulation* Boron Compounds / metabolism Boron Compounds / pharmacokinetics Cell Line, Tumor Cell Transformation, Neoplastic* Glioma / blood supply Glioma / diagnostic imaging Glioma / metabolism Glioma / pathology* Humans Large Neutral Amino Acid-Transporter 1 / metabolism* Male Pancreatic Neoplasms / blood supply Pancreatic Neoplasms / diagnostic imaging Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology* Phenylalanine / analogs & derivatives Phenylalanine / metabolism Phenylalanine / pharmacokinetics Positron-Emission Tomography* Radioactive Tracers Radiopharmaceuticals / metabolism Radiopharmaceuticals / pharmacokinetics* Rats Tissue Distribution Tyrosine / analogs & derivatives Tyrosine / metabolism Tyrosine / pharmacokinetics |
| IF | 1.648 |
| 引用数 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | RGC-6(RCB2783) |