title: Development of tyrosine-based radiotracer 99mTc-N4-Tyrosine for breast cancer imaging.
abstract: The purpose of this study was to develop an efficient way to synthesize (99m)Tc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-tyrosine ((99m)Tc-N4-Tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Precursor N4-Tyrosine was synthesized using a 5-step procedure, and its total synthesis yield was 38%. It was successfully labeled with (99m)Tc with high radiochemical purity (>95%). Cellular uptake of (99m)Tc-N4-Tyrosine was much higher than that of (99m)Tc-N4 and the clinical gold standard (18)F-2-deoxy-2-fluoro-glucose ((18)F-FDG) in rat breast tumor cells in vitro. Tissue uptake and dosimetry estimation in normal rats revealed that (99m)Tc-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that although (99m)Tc-N4-Tyrosine appeared to be inferior to (18)F-FDG in distinguishing breast tumor tissue from chemical-induced inflammatory tissue, it had high tumor-to-muscle uptake ratios and could detect breast tumors clearly by planar scintigraphic imaging. (99m)Tc-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging.
authors.affiliation: Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. kongfanlin2007@gmail.com
authors.forename: Fan-Lin
authors.initials: FL
authors.lastname: Kong
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Ali
authors.forename: Alex
authors.initials: A
authors.lastname: Rollo
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Smith
authors.forename: Yinhan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dong-Fang
authors.initials: DF
authors.lastname: Yu
authors.forename: David J
authors.initials: DJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011829:Radiation Dosage; D011849:Radioactive Tracers; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D015609:Organotechnetium Compounds; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; C045773:technetium Tc 99m cyclam; D019788:Fluorodeoxyglucose F18; D014443:Tyrosine