MR imaging of ovarian tumors using folate-receptor-targeted contrast agents.
BACKGROUND
Because of its over-expression in many human tumors, the folate receptor (FR) is a promising target for tumor-specific imaging.


OBJECTIVE
To evaluate the uptake of FR-targeted gadolinium (P866) and iron-oxide (P1048) agents in an ovarian tumor model.


METHODS
FR-positive ovarian cancer cells (IGROV-1) were incubated with FR-targeted agents (P866 or P1048) in the absence or presence of competing free folate. Intracellular gadolinium or iron-oxide concentrations were measured. MR imaging of implanted ovarian tumors in rats was performed following injection of FR-targeted (P866 and P1048) and nontargeted (P1001 and P904) agents. Changes in longitudinal and transverse relaxation rates (DeltaR1 and DeltaR2), which were proportional to the contrast agent concentration in the tumors, were compared between tumors injected with FR-targeted and nontargeted agents.


RESULTS
IGROV-1 cells showed uptake of P866 and P1048, which decreased with competing free folate. The DeltaR1 values were higher at 1 h following injection of P866 than following injection of P1001 (P < 0.05), indicating a higher amount of contrast agent retained in the tumor following P866 injection. There was a trend for higher DeltaR2 values at 48 h following injection of P1048 than following injection of P904, but it was not statistically significant (P = 0.09).


CONCLUSIONS
Specific accumulation of the FR-targeted gadolinium agent P866 was suggested in an FR-positive ovarian tumor model, demonstrating the possibility of combining the specificity of receptor targeting with the improved anatomic resolution of MR imaging. This could improve diagnosis and treatment of FR-positive tumors.
Wang
Zhen J
ZJ
Department of Radiology, University of California San Francisco, 505 Parnassus Ave., San Francisco, CA 94143-0628, USA. jane.wang@radiology.ucsf.edu
Boddington
Sophie
S
Wendland
Michael
M
Meier
Reinhard
R
Corot
Claire
C
Daldrup-Link
Heike
H
D000818:Animals; D002352:Carrier Proteins; D003287:Contrast Media / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D005290:Ferric Compounds; D058973:Folate Receptors, GPI-Anchored; D005682:Gadolinium; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology; D010053:Ovary / Q000473:pathology*; D051381:Rats; D011923:Rats, Nude; D011956:Receptors, Cell Surface; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D002352:Carrier Proteins; D003287:Contrast Media; D005290:Ferric Compounds; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; C000499:ferric oxide; D005682:Gadolinium