PT - JOURNAL ARTICLE AU - Kong, FanLin AU - Ali, Mohammad AU - Mendez, Richard AU - Yu, Dong-Fang AU - Yang, David TI - Synthesis and evaluation of <sup>99m</sup>Tc-N4-tyrosine for breast cancer imaging DP - 2012 May 01 TA - Journal of Nuclear Medicine PG - 1669--1669 VI - 53 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/53/supplement_1/1669.short 4100 - http://jnm.snmjournals.org/content/53/supplement_1/1669.full SO - J Nucl Med2012 May 01; 53 AB - 1669 Objectives This study was aimed to develop an efficient approach to synthesize 99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-tyrosine (99mTc-N4-tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Methods Precursor N4-tyrosine was synthesized by reacting N-BOC O-bromopropyl tyrosine methyl ester with N4-oxalate, followed by deprotection. Its structure was confirmed by NMR, HPLC and mass spectra. To assess the cellular uptake kinetics, the %uptake of 99mTc-N4-tyrosine was measured and compared with that of 99mTc-N4 and the clinical gold standard 18F-FDG in the rat breast cancer cell line 13762 at 0-4 h. Tissue distribution of 99mTc-N4-tyrosine was determined in normal rats up to 4 h after injection. To investigate whether 99mTc-N4-tyrosine can differentiate tumor from inflammation, tumor-to-inflammation ratios were determined in the rats carrying both tumor and turpentine-induced inflammation. Planar imaging of 99mTc-N4-tyrosine in tumor-bearing rats was performed at 0.5-4 h after injection. Results The total synthesis yield of N4-tyrosine was 38%. It was successfully labeled with 99mTc in a high radiochemical purity &gt;95% (by TLC and HPLC). Cellular uptake of 99mTc-N4-tyrosine was much higher than that of 99mTc-N4 and 18F-FDG in rat breast tumor cells. Tissue uptake and dosimetry estimation in normal rats revealed that 99mTc-N4-tyrosine could be safely administered to humans. Planar imaging in breast tumor-bearing rats showed that 99mTc-N4-tyrosine had high tumor-to-muscle uptake ratios and could clearly detect breast tumors. In addition, 99mTc-N4-tyrosine had more accumulation in breast tumor tissues than in chemical-induced inflammatory tissues. Conclusions We have successfully established a procedure for efficient synthesis of 99mTc-N4-tyrosine. Our in vitro and in vivo data collectively suggest that 99mTc-N4-tyrosine has great potential in breast tumor diagnostic imaging given its high tumor uptake