title: Synthesis and evaluation of amino acid-based radiotracer 99mTc-N4-AMT for breast cancer imaging.
abstract: OBJECTIVE
  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.affiliation: Department of Experimental Diagnostic Imaging, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. fanlin.kong@mdanderson.org
authors.forename: Fan-Lin
authors.initials: FL
authors.lastname: Kong
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Ali
authors.forename: Yinhan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chang-Sok
authors.initials: CS
authors.lastname: Oh
authors.forename: Dong-Fang
authors.initials: DF
authors.lastname: Yu
authors.forename: Mithu
authors.initials: M
authors.lastname: Chanda
authors.forename: David J
authors.initials: DJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D019805:alpha-Methyltyrosine / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C560570:technetium 99m O-(3-(1,4,8,11-tetraazabicyclohexadecane)propyl)-alpha-methyl tyrosine; D019805:alpha-Methyltyrosine