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Basic Science Investigations |
-Methyltyrosine After Preloading with Amino Acids: An In Vivo Animal Imaging Study
1 Division of Nuclear Medicine, Academic Hospital, Free University Brussels, Brussels, Belgium
3-123I-Iodo-L-
-methyltyrosine (3-IMT) is an amino acid analog used for tumor imaging. Specific accumulation is mediated mainly by the system L amino acid transport system. System L activity is known to increase when cells are loaded with amino acids. The aim of our study was to measure the effects of amino acid preload on 123I-3-IMT tumor uptake and image contrast in a rat tumor model using in vivo dynamic imaging. Methods: Rhabdomyosarcoma (R1M) tumor-bearing rats underwent 2 dynamic 123I-3-IMT studies on separate days: 1 baseline study and 1 after intraperitoneal injection (0.25 mmol/kg) of a single amino acid (arginine, proline, glutamate, asparagine, tryptophan, or phenylalanine) administered 30 min before intravenous injection of 18.5 MBq 123I-3-IMT. A 99mTc-labeled human serum albumin study was performed on each rat for the calculation of the blood-pool activity inside the tumor. Time-activity curves were generated for tumor, contralateral background region, kidney, heart, and total body. Tumor uptake was corrected for blood-pool and background activity. Image contrast was calculated as the ratio between tumor and background activity. The rate (K1) of tracer entering the tumor was obtained using Patlak analysis. A displacement study was performed on a separate group of rats, in which a high dose of phenylalanine was administered 40 min after 123I-3-IMT injection. Results: 123I-3-IMT accumulation in tumor reached a plateau 10 min after injection. Tumor uptake on the baseline scans correlated well with tumor size (r = 0.92). After preloading, tumor uptake and contrast increased in all conditions: arginine, +26% and +26%; proline, +15% and +13%; glutamate, +14% and +9%; asparagine, +19% and +15%; tryptophan, +36% and 11%; phenylalanine, +22% and + 13%. K1 values also increased. Administration of an afterload with phenylalanine induced a significant displacement of 123I-3-IMT tumor accumulation. Conclusion: Prior amino acid administration increases 123I-3-IMT tumor accumulation and image contrast. This effect can be explained by the increased antiporter activity of the amino acid transport system L in preloaded conditions. Our results indicate that the fasted state might not be the optimal metabolic condition to study tumor accumulation of L-transported tracers such as 123I-3-IMT. Amino acid administration before 123I-3-IMT injection could improve tumor uptake and image contrast.
Key Words: 3-123I-iodo-L--methyltyrosine • tumor imaging • system L • amino acid preload
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