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Synthesis of \u3csup\u3e99m\u3c/sup\u3eTc-EC-AMT as an imaging probe for amino acid transporter systems in breast cancer
Authors
Mohammad S. Ali
Mithu Chanda
+6 more
Saady Kohanim
Fan Lin Kong
Richard Mendez
Chanksok Oh
Ning Tsao
Yinhan Zhang
Publication date
1 August 2010
Publisher
'Ovid Technologies (Wolters Kluwer Health)'
Doi
Cite
Abstract
Objective: This study was to develop a 99mTc-labeled α-methyl tyrosine (AMT) using L,L-ethylenedicysteine (EC) as a chelator and to evaluate its potential in breast tumor imaging in rodents. METHODS: EC-AMT was synthesized by reacting EC and 3-bromopropyl AMT (N-BOC, ethyl ester) in ethanol/potassium carbonate solution. EC-AMT was labeled with Tc in the presence of tin (II) chloride. Rhenium-EC-AMT (Re-EC-AMT) was synthesized as a reference standard for 99mTc-EC-AMT. To assess the cellular uptake kinetics of 99mTc-EC-AMT, 13762 rat breast cancer cells were incubated with 99mTc-EC-AMT for 0-2h. To investigate the transport mechanism, the same cell line was used to conduct the competitive inhibition study using L-tyrosine. Tissue distribution of 99mTc-EC-AMT was determined in normal rats at 0.5-4h. Planar imaging of breast tumor-bearing rats was performed at 30 and 90min. The data were compared with those of 18F-2-fluoro-2-deoxy-glucose. Blocking uptake study using unlabeled AMT was conducted to investigate the transport mechanism of 99mTc-EC- AMT in vivo. Results: Structures of EC-AMT and Re-EC-AMT were confirmed by nuclear magnetic resonance, high performance liquid chromatography and mass spectra. In-vitro cellular uptake of 99mTc-EC-AMT in 13762 cells was increased as compared with that of 99mTc-EC and could be inhibited by L-tyrosine. Biodistribution in normal rats showed high in-vivo stability of 99mTc-EC-AMT. Planar scintigraphy at 30 and 90min showed that 99mTc-EC-AMT could clearly visualize tumors. 99mTc-EC-AMT uptake could be significantly blocked by unlabeled AMT in vivo. Conclusion: The results indicate that 99mTc-EC-AMT, a new amino acid transporter-based radiotracer, is suitable for breast tumor imaging. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
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Last time updated on 26/07/2022