Abstract
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Objectives: This study was aimed to develop a kit-based 99mTc α-methyl-D, L-tyrosine (AMT) using N4 (cyclam) as a chelator and evaluate its potential use for imaging mammary tumors.
Methods: N4-AMT precursor was synthesized by reacting trifloroacetylated N4 and N-t-butoxycarbonyl-O-3-tosylpropyl-AMT, followed by acidic and then basic hydrolysis. 99mTc N4-AMT was obtained in the presence of tin (II) chloride. To demonstrate whether an amino acid transporter was involved, in vitro cellular uptake of 99mTc N4-AMT (0.1 mg in 1 uCi/well) with or without blocking agents (0.5 or 1 mg/well of AMT) were performed in 13762 mammary adenocarcinoma cells (5*104 cells /well) at 0.5-1.5 hrs. Planar scintigraphic imaging with injection of 99mTc N4 or 99mTc N4-AMT were evaluated in ovarian tumor–bearing athymic nude mice and VX2 tumor-bearing rabbits (1mCi, iv) at 0.5-4 hrs.
Results: N4-AMT was confirmed by 1H, 13C-NMR and mass spectrometry. Radiochemical purity of 99mTc N4-AMT was > 96 %. Cellular uptake assays showed a significant increase in the 13762 cell line by 1.6% after 1.5 hr incubation with 99mTc N4-AMT. Blocking study with cold AMT (0.5 and 1.0 mg) at 90 min showed that the uptake rate decreased 22-68%, respectively. These findings support that 99mTc N4-AMT may utilize the tyrosine transport system to get into the cell. The tumors of nude mice and rabbit models were clearly visualized in planar scintigraphy by 99mTc N4-AMT but not 99mTc N4.
Conclusions: N4-AMT was successfully synthesized and easily radiolabeled by 99mTc. We conclude that an amino acid transporter-based 99mTc N4-AMT is a useful marker for tumor imaging.
- Society of Nuclear Medicine, Inc.