title: 99mTc(CO)3-DTMA bombesin conjugates having high affinity for the GRP receptor.
abstract: BACKGROUND
  Targeted diagnosis of specific human cancer types continues to be of significant interest in nuclear medicine. 99mTc is ideally suited as a diagnostic radiometal for in vivo tumor targeting due to its ideal physical characteristics and diverse labeling chemistries in numerous oxidation states.
  
  
  METHODS
  In this study, we report a synthetic approach toward design of a new tridentate amine ligand for the organometallic aqua-ion [99mTc(H2O)3(CO)3]+. The new chelating ligand framework, 2-(N,N'-Bis(tert-butoxycarbonyl)diethylenetriamine) acetic acid (DTMA), was synthesized from a diethylenetriamine precursor and fully characterized by mass spectrometry and nuclear magnetic resonance spectroscopy (1H and 13C). DTMA was conjugated to H2N-(X)-BBN(7-14)NH2, where X=an amino acid or aliphatic pharmacokinetic modifier and BBN=bombesin peptide, by means of solid phase peptide synthesis. DTMA-(X)-BBN(7-14)NH2 conjugates were purified by reversed-phase high-performance chromatography and characterized by electrospray-ionization mass spectrometry.
  
  
  RESULTS
  The new conjugates were radiolabeled with [99mTc(H2O)3(CO)3]+ produced via Isolink radiolabeling kits to produce [99mTc(CO)3-DTMA-(X)-BBN(7-14)NH2]. Radiolabeled conjugates were purified by reversed-phase high-performance chromatography. Effective receptor binding behavior was evaluated in vitro and in vivo.
  
  
  CONCLUSIONS
  [99mTc(CO)3-DTMA-(X)-BBN(7-14)NH2] conjugates displayed very high affinity for the gastrin releasing peptide receptor in vitro and in vivo. Therefore, these conjugates hold some propensity to be investigated as molecular imaging agents that specifically target human cancers uniquely expressing the gastrin releasing peptide receptor subtypes.
authors: Research Division, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.
authors: Stephanie R
authors: SR
authors: Lane
authors: Bhadrasetty
authors: B
authors: Veerendra
authors: Tammy L
authors: TL
authors: Rold
authors: Gary L
authors: GL
authors: Sieckman
authors: Timothy J
authors: TJ
authors: Hoffman
authors: Silvia S
authors: SS
authors: Jurisson
authors: Charles J
authors: CJ
authors: Smith
mesh_terms: D000085:Acetates / Q000378:metabolism* / Q000493:pharmacokinetics*; D019342:Acetic Acid / Q000737:chemistry; D000818:Animals; D001667:Binding, Competitive; D001839:Bombesin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002414:Cations, Monovalent / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011073:Polyamines / Q000737:chemistry* / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D018004:Receptors, Bombesin / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000085:Acetates; D002352:Carrier Proteins; D002414:Cations, Monovalent; D002614:Chelating Agents; D015609:Organotechnetium Compounds; D011073:Polyamines; D019275:Radiopharmaceuticals; D018004:Receptors, Bombesin; C005391:diethylenetriamine; D013667:Technetium; D001839:Bombesin; D019342:Acetic Acid