Synthesis and evaluation of amino acid-based radiotracer 99mTc-N4-AMT for breast cancer imaging.

Abstract

PURPOSE:

This study was to develop an efficient synthesis of (99m)Tc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-α-methyl tyrosine ((99m)Tc-N4-AMT) and evaluate its potential in cancer imaging.

METHODS:

N4-AMT was synthesized by reacting N4-oxalate and 3-bromopropyl AMT (N-BOC, ethyl ester). In vitro cellular uptake kinetics of (99m)Tc-N4-AMT was assessed in rat mammary tumor cells. Tissue distribution of the radiotracer was determined in normal rats at 0.5-4 h, while planar imaging was performed in mammary tumor-bearing rats at 30-120 min.

RESULTS:

The total synthesis yield of N4-AMT was 14%. Cellular uptake of (99m)Tc-N4-AMT was significantly higher than that of (99m)Tc-N4. Planar imaging revealed that (99m)Tc-N4-AMT rendered greater tumor/muscle ratios than (99m)Tc-N4.

CONCLUSIONS:

N4-AMT could be synthesized with a considerably high yield. Our in vitro and in vivo data suggest that (99m)Tc-N4-AMT, a novel amino acid-based radiotracer, efficiently enters breast cancer cells, effectively distinguishes mammary tumors from normal tissues, and thus holds the promise for breast cancer imaging.

• Authors: Fan-Lin Kong, Mohammad S Ali, Yinhan Zhang, Chang-Sok Oh, Dong-Fang Yu, Mithu Chanda, David J Yang
• Journal: Journal of biomedicine & biotechnology (J Biomed Biotechnol) Vol. 2011 Pg. 276907 ( 2011) ISSN: 1110-7251 [Electronic] United States
• PMID: 21541217 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Organotechnetium Compounds
• Radiopharmaceuticals
• technetium 99m O-(3-(1,4,8,11-tetraazabicyclohexadecane)propyl)-alpha-methyl tyrosine
• alpha-Methyltyrosine

Topics

• Animals
• Breast Neoplasms (diagnostic imaging, pathology)
• Cell Line, Tumor
• Chromatography, High Pressure Liquid
• Female
• Organotechnetium Compounds (chemical synthesis, chemistry, pharmacokinetics)
• Radionuclide Imaging (methods)
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)
• Rats
• Rats, Inbred F344
• Tissue Distribution
• alpha-Methyltyrosine (chemical synthesis, chemistry, pharmacokinetics)