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

作者：Kalber Tammy L^*; Kamaly Nazila; So Po Wah; Pugh John A; Bunch Josephine; McLeod Cameron W; Jorgensen Michael R; Miller Andrew D; Bell Jimmy D

来源：Molecular Imaging and Biology, 2011, 13(4): 653-662.

DOI：10.1007/s11307-010-0400-3

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

This study aims to develop a low molecular weight folate receptor (FR) contrast agent for MR tumor imaging.
Gadolinium-tetraazacyclododecane tetraacetic acid (Gd.DOTA) was conjugated to folic 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 resonance imaging (MRI) tumor enhancement over 14 h, utilizing an overexpressing alpha-FR cell line (IGROV-1), compared to an alpha-FR-negative cell line (OVCAR-3). Gd.DOTA.Folate localization ex vivo was verified by laser ablation ICP-MS.
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 R (1) 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.
These data support the use of FR-targeted small molecular weight MRI contrast agents for tumor imaging in vivo.

• 出版日期2011-8