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Development of (99m)Tc-EC-tyrosine for early detection of breast cancer tumor response to the anticancer drug melphalan.
- Source :
- Academic Radiology; Jan2013, Vol. 20 Issue 1, p41-51, 11p
- Publication Year :
- 2013
-
Abstract
- <bold>Rationale and Objectives: </bold>Radiolabeled tyrosine analogues that have been successfully used in tumor imaging accumulate in tumor cells via an upregulated L-type amino acid transporter system. The anticancer drug melphalan is an L-type amino acid transporter substrate. Therefore, radiolabeled tyrosine analogues may have great potential in evaluating treatment responses to melphalan. In this study, a (99m)Tc-labeled tyrosine analogue, (99m)Tc tyrosine using N,N'-ethylene-di-L-cysteine (EC) as a chelator, was developed and its potential for noninvasively assessing tumors' early response to melphalan determined.<bold>Materials and Methods: </bold>EC-tyrosine was synthesized in a three-step procedure and labeled with (99m)Tc. To assess cellular uptake kinetics, the percentage uptake of (99m)Tc-EC-tyrosine in the rat breast cancer cell line 13762 was measured. Planar imaging was performed in rats with 13762 cell-derived tumors. To determine the transport mechanisms of (99m)Tc-EC-tyrosine, a competitive inhibition study using L-tyrosine as an inhibitor was performed in vitro and in vivo. To assess tumors' response to melphalan, tumor-bearing rats were treated with different doses of melphalan, and planar imaging was performed 0 and 3 days after treatment. Immunohistochemical analyses were conducted to determine expressions of L-type amino acid transporter 1 and cellular proliferation marker Ki-67.<bold>Results: </bold>L-tyrosine significantly inhibited (99m)Tc-EC-tyrosine uptake in vitro and in vivo. Tumor volume decreased in a dose-dependent manner with melphalan, and tumor/muscle ratios of (99m)Tc-EC-tyrosine were significantly reduced in treated groups. Immunohistochemical data indicated that about 70% of tumor cells in the melphalan-treated groups underwent apoptosis, and the changes in tumor/muscle ratios reflected the decreased percentage of viable cells in treated tumors.<bold>Conclusions: </bold>These findings suggest that (99m)Tc-EC-tyrosine has great potential for monitoring tumor response to melphalan in breast tumor-bearing rats. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10766332
- Volume :
- 20
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Academic Radiology
- Publication Type :
- Academic Journal
- Accession number :
- 104402460
- Full Text :
- https://doi.org/10.1016/j.acra.2012.08.005