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

Kalber, Tammy L.; Kamaly, Nazila; So, Po‐Wah; Pugh, John; Bunch, Josephine; McLeod, Cameron W.; Jorgensen, Matthew R.; Miller, Andrew D.; Bell, Jimmy D.

doi:10.1007/s11307-010-0400-3

Cited by 31 publications

(27 citation statements)

References 33 publications

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“…14,15 The distribution of Pt, Se, 14 Gd, and Lu 18 has also been mapped following in vivo administration of respective metal containing compounds.…”

mentioning

confidence: 99%

Combined Elemental and Biomolecular Mass Spectrometry Imaging for Probing the Inventory of Tissue at a Micrometer Scale

Matusch¹,

Fenn

Depboylu³

et al. 2012

Anal. Chem.

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Several complementary mass spectrometric imaging techniques allow mapping of various analytes within biological tissue sections. Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) quantitatively detects elements and isotopes with very high sensitivity and a particularly high dynamical range. Matrix-assisted laser desorption/ionization ion mobility mass spectrometry (MALDI-IM-MS) allows a pixel-by-pixel classification and identification of biomolecules.In order to dispose of the healthy hemisphere as an internal calibrant in addition to routinely used external standards, adjacent brain sections of mice with a unilateral 6-OHDA lesion of the medial forebrain bundle were chosen as exemplary samples. We demonstrate a comprehensive way of data acquisition and analysis by coregistering mass spectrometric data on photomicrographs as common reference space and thus providing trimodal spatial information. Registering subsequent planar element maps yielded continuous 3-dimensional data sets. Furthermore, we introduce a correction of MSI data for variable slice thickness applicable to all MSI techniques. In the present case, we observed increased concentrations of iron, manganese, and copper in the lesioned substantia nigra while monounsaturated lipid levels were decreased in the identical region of interest. Our techniques provide new insights into the intricate spatial relationship of morphology and chemistry within tissue.

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“…14,15 The distribution of Pt, Se, 14 Gd, and Lu 18 has also been mapped following in vivo administration of respective metal containing compounds.…”

mentioning

confidence: 99%

Combined Elemental and Biomolecular Mass Spectrometry Imaging for Probing the Inventory of Tissue at a Micrometer Scale

Matusch¹,

Fenn

Depboylu³

et al. 2012

Anal. Chem.

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“…A range of other 'targeted' contrast agents are under development for both MRI and ultrasound imaging. [33][34][35] While there are numerous studies that have used DCE-MRI to obtain tumor information based on vascular differences, 36,37 our results suggest that targeted contrast agents that interact directly with tissues could yield significant functional information if combined with dynamic contrast approaches.…”

Section: Discussionmentioning

confidence: 75%

Dynamic contrast-enhanced optical imaging of in vivo organ function

et al. 2012

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Abstract. Conventional approaches to optical small animal molecular imaging suffer from poor resolution, limited sensitivity, and unreliable quantitation, often reducing their utility in practice. We previously demonstrated that the in vivo dynamics of an injected contrast agent could be exploited to provide high-contrast anatomical registration, owing to the temporal differences in each organ's response to the circulating fluorophore. This study extends this approach to explore whether dynamic contrast-enhanced optical imaging (DyCE) can allow noninvasive, in vivo assessment of organ function by quantifying the differing cellular uptake or wash-out dynamics of an agent in healthy and damaged organs. Specifically, we used DyCE to visualize and measure the organ-specific uptake dynamics of indocyanine green before and after induction of transient liver damage. DyCE imaging was performed longitudinally over nine days, and blood samples collected at each imaging session were analyzed for alanine aminotransferase (ALT), a liver enzyme assessed clinically as a measure of liver damage. We show that changes in DyCE-derived dynamics of liver and kidney dye uptake caused by liver damage correlate linearly with ALT concentrations, with an r 2 value of 0.91. Our results demonstrate that DyCE can provide quantitative, in vivo, longitudinal measures of organ function with inexpensive and simple data acquisition.

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“…Folate-conjugated monomeric contrast agent 6 (Fig. 2) has a low relaxivity of 1.28 mM −1 s −1 (4.7 T and aqueous solution) [29]. In vitro studies of 6 with human folate-receptor-positive ovarian carcinoma (IGROV-1) cell lines did not produce signal enhancement; however, inductively coupled plasma-mass spectrometry results with competitive binding experiments confirmed the uptake of 6 by the cells.…”

Section: The Conjugation Strategymentioning

confidence: 99%

Strategies for Target-Specific Contrast Agents for Magnetic Resonance Imaging

Vithanarachchi¹,

Allen²

2012

CMI

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This review describes recent research efforts focused on increasing the specificity of contrast agents for proton magnetic resonance imaging (MRI). Contrast agents play an indispensable role in MRI by enhancing the inherent contrast of images; however, the non-specific nature of current clinical contrast agents limits their usefulness. This limitation can be addressed by conjugating contrast agents or contrast-agent-loaded carriers—including polymers, nanoparticles, dendrimers, and liposomes—to molecules that bind to biological sites of interest. An alternative approach to conjugation is synthetically mimicking biological structures with metal complexes that are also contrast agents. In this review, we describe the advantages and limitations of these two targeting strategies with respect to translation from in vitro to in vivo imaging while focusing on advances from the last ten years.

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

Abstract: These data support the use of FR-targeted small molecular weight MRI contrast agents for tumor imaging in vivo.

Cited by 31 publications

References 33 publications

Combined Elemental and Biomolecular Mass Spectrometry Imaging for Probing the Inventory of Tissue at a Micrometer Scale

Combined Elemental and Biomolecular Mass Spectrometry Imaging for Probing the Inventory of Tissue at a Micrometer Scale

Dynamic contrast-enhanced optical imaging of in vivo organ function

Strategies for Target-Specific Contrast Agents for Magnetic Resonance Imaging

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