Increased tumor uptake of 3-(123)I-Iodo-L-alpha-methyltyrosine after preloading with amino acids: an in vivo animal imaging study.
3-(123)I-Iodo-L-alpha-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 (123)I-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 (123)I-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 (123)I-3-IMT. A (99m)Tc-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 (K(1)) 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 (123)I-3-IMT injection.


RESULTS
(123)I-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%. K(1) values also increased. Administration of an afterload with phenylalanine induced a significant displacement of (123)I-3-IMT tumor accumulation.


CONCLUSIONS
Prior amino acid administration increases (123)I-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 (123)I-3-IMT. Amino acid administration before (123)I-3-IMT injection could improve tumor uptake and image contrast.
Lahoutte
Tony
T
Division of Nuclear Medicine, Academic Hospital, Free University Brussels, Brussels, Belgium. tony.lahoutte@az.vub.ac.be
Caveliers
Vicky
V
Franken
Philippe R
PR
Bossuyt
Axel
A
Mertens
John
J
Everaert
Hendrik
H
D000596:Amino Acids / Q000493:pharmacokinetics; D000818:Animals; D007457:Iodine Radioisotopes; D008297:Male; D008781:Methyltyrosines / Q000493:pharmacokinetics*; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D013668:Technetium Tc 99m Aggregated Albumin
D000596:Amino Acids; D007457:Iodine Radioisotopes; D008781:Methyltyrosines; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; C030855:3-iodo-alpha-methyltyrosine