title: Biodistribution of a 153 Gd-folate dendrimer, generation = 4, in mice with folate-receptor positive and negative ovarian tumor xenografts.
abstract: OBJECTIVE
  An important characteristic of targeted contrast agents is how they are tolerated in a biologic environment and their localization in the surrounding tissues in addition to target tissue. We evaluate the biodistribution of a gadolinium Gd 153-folate-dendrimer in high affinity folate-receptor (hFR) positive and negative ovarian tumor xenografts.
  
  
  METHODS
  The 153Gd-folate-dendrimer chelate was prepared by exchanging 153Gd with nonradioactive gadolinium for 1 week, followed by extensive filtration. Athymic mice with hFR-positive (n = 3) and negative tumors (n = 3) were injected intravenously and counted using a whole-body counting system with a 80 to 150 keV counting window.
  
  
  RESULTS
  The hFR-positive tumors accumulate 3.6% +/- 2.8% injected dose/g, whereas only background counts were found in hFR-negative tumors. The folate-dendrimer's tumor-to-blood ratio of 12.6, in hFR-positive tumors, was approximately 5.7 to 17.0 fold better than those obtained with monoclonal antibodies targeted to the folate receptor.
  
  
  CONCLUSIONS
  Biodistribution studies confirm previous MRI findings and show that the accumulation of the folate-dendrimer requires the expression of the hFR.
authors.affiliation: Beckman Institute, Urbana, Illinois 61801, USA.
authors.forename: Sheela D
authors.initials: SD
authors.lastname: Konda
authors.forename: Steven
authors.initials: S
authors.lastname: Wang
authors.forename: Martin
authors.initials: M
authors.lastname: Brechbiel
authors.forename: Erik C
authors.initials: EC
authors.lastname: Wiener
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002614:Chelating Agents; D003287:Contrast Media / Q000378:metabolism*; D050091:Dendrimers; D004305:Dose-Response Relationship, Drug; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D019786:Gadolinium DTPA / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011073:Polyamines; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D002614:Chelating Agents; D003287:Contrast Media; D050091:Dendrimers; D058973:Folate Receptors, GPI-Anchored; C104700:PAMAM Starburst; D011073:Polyamines; D011956:Receptors, Cell Surface; D005492:Folic Acid; D019786:Gadolinium DTPA