Biodistribution of a 153 Gd-folate dendrimer, generation = 4, in mice with folate-receptor positive and negative ovarian tumor xenografts.
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.
Konda
Sheela D
SD
Beckman Institute, Urbana, Illinois 61801, USA.
Wang
Steven
S
Brechbiel
Martin
M
Wiener
Erik C
EC
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
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