A Low Molecular Weight Folate Receptor Targeted Contrast Agent for Magnetic Resonance Tumor Imaging

T. L. Kalber, Nazila Kamaly, Po-Wah So, John A. Pugh, Josephine Bunch, Cameron W. McLeod, Michael R. Jorgensen, Andrew D. Miller, Jimmy D. Bell

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Purpose: This study aims to develop a low molecular weight folate receptor (FR) contrast agent for MR tumor imaging.
Procedures: Gadolinium-tetraazacyclododecane tetraacetic acid (Gd.DOTA) was conjugated tofolic acid to create Gd.DOTA.Folate. The efficacy of Gd.DOTA.Folate to bind FR was evaluated in vitro by inductively coupled mass spectrometry (ICP-MS) and in vivo by magnetic resonanceimaging (MRI) tumor enhancement over 14 h, utilizing an overexpressing α-FR cell line (IGROV-1), compared to an α-FR-negative cell line (OVCAR-3). Gd.DOTA.Folate localization ex vivo was verified by laser ablation ICP-MS.
Results: ICP-MS confirmed Gd.DOTA.Folate uptake by IGROV-1 cells and competitive binding with free folic acid inhibited binding. IGROV-1 tumors showed an increase in R1 at 2 h, which increased significantly over 14 h post-Gd.DOTA.Folate with clear enhancement on MR images. This was not observed in controls.
Conclusion: These data support the use of FR-targeted small molecular weight MRI contrast agents for tumor imaging in vivo.
Original languageEnglish
JournalMolecular Imaging and Biology
Pages (from-to)653-662
ISSN1536-1632
DOIs
Publication statusPublished - 2010
Externally publishedYes

Keywords

  • Folate receptor targeting
  • Folate
  • MRI contrast agents
  • Low molecular weight contrast agents
  • Tumor MRI
  • Tumor imaging
  • Gadolinium contrast agents

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