title: Effects of chelator modifications on (68)Ga-labeled [Tyr (3)]octreotide conjugates.
abstract: OBJECTIVE
  Somatostatin receptors (SSTR) have been reported as promising targets for imaging agents for cancer. Recently, (68)Ga-DOTATOC-based PET imaging has been used successfully for diagnosis and management of SSTR-expressing tumors. The purpose of this study was to evaluate the influence of chelator modifications and charge on (68)Ga-labeled peptide conjugates.
  
  
  METHODS
  We have synthesized a series of [Tyr(3)]octreotide conjugates that consisted of different NOTA-based chelators with two to five carboxylate moieties, and compared our results with (68)Ga-DOTATOC in both in vitro and in vivo studies.
  
  
  RESULTS
  With the exception of (68)Ga-1 (three carboxylates), the increased number of carboxylates on the NOTA-based chelators resulted in a reduced binding affinity and internalization. Additionally, the tumor uptake for (68)Ga-2 (four carboxylates) and (68)Ga-3 (five carboxylates) was reduced compared to that of (68)Ga-DOTATOC (three carboxylates) and (68)Ga-NO2ATOC (two carboxylates) and (68)Ga-1 (three carboxylates) at 2 h p.i. suggesting the presence of an optimal charge for this compound.
  
  
  CONCLUSIONS
  Chelator modifications can lead to the altered pharmacokinetics. These results may impact further design considerations for peptide-based imaging agents.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box.8225, 510 South Kingshighway Blvd, St. Louis, MO, 63110, USA.
authors.forename: Mai
authors.initials: M
authors.lastname: Lin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Lapi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry*; D004705:Endocytosis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D015282:Octreotide / Q000031:analogs & derivatives* / Q000737:chemistry; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000737:chemistry; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism; D013194:Staining and Labeling; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: C550726:68Ga-octreotide, DOTA(0)-Tyr(3)-; D002614:Chelating Agents; D009942:Organometallic Compounds; D017481:Receptors, Somatostatin; D015282:Octreotide