Development of a tumor-targeting MR contrast agent using the high-affinity folate receptor: work in progress.
OBJECTIVE
Macromolecular contrast agents enhance tumors by means of active or passive targeting. Active targeting requires surface receptors. Many tumors of epithelial origin express the high-affinity folate receptor (hFR), including ovarian tumors. The objective of this research was to enhance tumors that express hFR using macromolecular contrast agents conjugated to folic acid.


METHODS
The authors prepared a folate-conjugated dendrimer polychelate by attaching folic acid to a fourth-generation ammonia-core polyamidoamine dendrimer. The remaining amines were reacted with 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriamine pentaacetic acid. Relaxivity measurements (r1 and r2) and MRI were conducted at 4.7 T.


RESULTS
The dendrimer r2 exceeded that of Gd-HP-DO3A by 8.2 times at 4.7 T. It increased the tumor percentage contrast enhancement, 24 hours after injection, of T2-weighted images by 33%.


CONCLUSIONS
This new agent accumulates in tumors expressing hFR. These results do not differentiate between active and passive targeting mechanisms. Receptor-negative tumors suggest a mechanism other than a nonspecific blood pool effect.
Konda
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SD
Biomedical Magnetic Resonance Laboratory, College of Medicine, and the Beckman Institute, University of Illinois, Urbana-Champaign, USA.
Aref
M
M
Brechbiel
M
M
Wiener
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EC
D000818:Animals; D002352:Carrier Proteins; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics; D010051:Ovarian Neoplasms / Q000175:diagnosis*; D011956:Receptors, Cell Surface
D002352:Carrier Proteins; D003287:Contrast Media; D058973:Folate Receptors, GPI-Anchored; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D011956:Receptors, Cell Surface; C062402:gadoteridol; D005492:Folic Acid; D005682:Gadolinium