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 99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-α-methyl tyrosine (99mTc-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 99mTc-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 99mTc-N4-AMT was significantly higher than that of 99mTc-N4. Planar imaging revealed that 99mTc-N4-AMT rendered greater tumor/muscle ratios than 99mTc-N4. Conclusions. N4-AMT could be synthesized with a considerably high yield. Our in vitro and in vivo data suggest that 99mTc-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.

Development of Tyrosine-Based RadiotracerTc99m-N4-Tyrosine for Breast Cancer Imaging

“…13 C- NMR results (D 2 O δ , ppm) were as follows: 162.88, 156.72, 130.76, 117.57, 115.25, 68.55, 57.29, 53.91, 51.56, 49.95, 49.17, 48.96, 48.24, 48.03, 46.80, 45.73, 45.35, 39.27, 24.90, 24.31, and 23.87. Because the starting material, N- t -butoxycarbonyl-L-tyrosine methyl ester, was commercially available, the synthetic yield of N4-Tyrosine in our study was much higher (38%) than that of its α -methyl derivative N4-AMT (14%), which was reported in a previous study [ 14 ].…”

“…High uptake was found in the kidneys, which was consistent with the planar scintigraphic imaging findings in the breast tumor-bearing rats (see Figure 5 ). This high kidney uptake may be a result of the low lipophilicity of 99m Tc-N4-Tyrosine, or it may be related to the biological characteristics of 99m Tc-labeled tyrosine because similar results were also observed in the previously developed tyrosine-based radiotracers 99m Tc-N4-AMT, 99m Tc-EC-AMT, and 99m Tc-EC-Tyrosine [ 14 , 15 ].…”

Synthesis and Biological Evaluation of O-[3-18F-fluoropropyl]-α-methyl Tyrosine in Mesothelioma-Bearing Rodents

“…N-t-butoxycarbonyl-O-[3-hydroxypropyl]- α -methyl tyrosine ethyl ester, which we used as the precursor compound for synthesis of 19 F-FPAMT and 18 F-FPAMT, was prepared as described previously [17]. Briefly, N-t-butoxycarbonyl-O-[3-hydroxypropyl]- α -methyl tyrosine ethyl ester (490 mg; 1.28 mmol) in anhydrous pyridine (32 mL) was cooled to 0°C.…”

Amino Acid Metabolism as a Target for Breast Cancer Imaging

“…20 99mTc-labeled tyrosine analogs have also been synthesized with high yield and distinguish breast malignancies from benign breast tissues. 49,50 Propanoic acid amino acid analogs, primarily dependent on system A transport, have been developed by the same group at Emory that synthesized 18 F-fluciclovine. 51 In preclinical studies, multiple propanoic acid derivatives demonstrated good tumor uptake in human-derived breast cancer cells, as well as in mouse tumor xenografts.…”