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

doi:10.1007/s11307-010-0400-3

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 journal › Journal article › Research › peer-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 language	English
Journal	Molecular Imaging and Biology
Pages (from-to)	653-662
ISSN	1536-1632
DOIs	https://doi.org/10.1007/s11307-010-0400-3
Publication status	Published - 2010
Externally published	Yes

Keywords

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

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10.1007/s11307-010-0400-3

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@article{1a049b82a34d420fbfb51e7818d31a6c,

title = "A Low Molecular Weight Folate Receptor Targeted Contrast Agent for Magnetic Resonance Tumor Imaging",

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.",

keywords = "Folate receptor targeting, Folate, MRI contrast agents, Low molecular weight contrast agents, Tumor MRI, Tumor imaging, Gadolinium contrast agents",

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

year = "2010",

doi = "10.1007/s11307-010-0400-3",

language = "English",

pages = "653--662",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer New York",

}

TY - JOUR

T1 - A Low Molecular Weight Folate Receptor Targeted Contrast Agent for Magnetic Resonance Tumor Imaging

AU - Kalber, T. L.

AU - Kamaly, Nazila

AU - So, Po-Wah

AU - Pugh, John A.

AU - Bunch, Josephine

AU - McLeod, Cameron W.

AU - Jorgensen, Michael R.

AU - Miller, Andrew D.

AU - Bell, Jimmy D.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Folate receptor targeting

KW - Folate

KW - MRI contrast agents

KW - Low molecular weight contrast agents

KW - Tumor MRI

KW - Tumor imaging

KW - Gadolinium contrast agents

U2 - 10.1007/s11307-010-0400-3

DO - 10.1007/s11307-010-0400-3

M3 - Journal article

SN - 1536-1632

SP - 653

EP - 662

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

ER -

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

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