In vivo imaging of human breast cancer mouse model with high level expression of calcium sensing receptor at 3T

Baio, Gabriella; Fabbi, Marina; Emionite, Laura; Cilli, Michele; Salvi, Sandra; Ghedin, P.; Prato, Sabina; Carbotti, Grazia; Tagliafico, Alberto; Truini, Mauro; Neumaier, Carlo Emanuele

doi:10.1007/s00330-011-2285-1

Cited by 10 publications

(22 citation statements)

References 47 publications

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“…Treatments with Verapamil were also performed in order to evaluate the role of the Calcium-Sensing Receptor (CaSR) in the release of Mn 2+ ions out of the cancer cells19. This treatment enabled to retain Mn 2+ ions into the metastatic cells, shown by a 34.1% T1 value shortening (Table 1).…”

Section: Resultsmentioning

confidence: 99%

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In vivo MEMRI characterization of brain metastases using a 3D Look-Locker T1-mapping sequence

Castets

Koonjoo

Hertanu

et al. 2016

Sci Rep

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Although MEMRI (Manganese Enhanced MRI) informations were obtained on primary tumors in small animals, MEMRI data on metastases are lacking. Thus, our goal was to determine if 3D Look-Locker T1 mapping was an efficient method to evaluate Mn ions transport in brain metastases in vivo. The high spatial resolution in 3D (156 × 156 × 218 μm) of the sequence enabled to detect metastases of 0.3 mm3. In parallel, the T1 quantitation enabled to distinguish three populations of MDA-MB-231 derived brain metastases after MnCl2 intravenous injection: one with a healthy blood-tumor barrier that did not internalize Mn2+ ions, and two others, which T1 shortened drastically by 54.2% or 24%. Subsequent scans of the mice, enabled by the fast acquisition (23 min), demonstrated that these T1 reached back their pre-injection values in 24 h. Contrarily to metastases, the T1 of U87-MG glioma remained 26.2% shorter for one week. In vitro results supported the involvement of the Transient Receptor Potential channels and the Calcium-Sensing Receptor in the uptake and efflux of Mn2+ ions, respectively. This study highlights the ability of the 3D Look-Locker T1 mapping sequence to study heterogeneities (i) amongst brain metastases and (ii) between metastases and glioma regarding Mn transport.

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Section: Resultsmentioning

confidence: 99%

“…Some have noted a difference in manganese uptake between malignant and normal cells18. Baio et al 19. detected a high accumulation of Mn 2+ ions in breast cancer cells expressing high levels of the Calcium-Sensing Receptor (CaSR).…”

mentioning

confidence: 99%

In vivo MEMRI characterization of brain metastases using a 3D Look-Locker T1-mapping sequence

Castets

Koonjoo

Hertanu

et al. 2016

Sci Rep

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“…Unlike gadolinium, a paramagnetic lanthanide ion approved for clinical use, manganese is an endogenous constituent and behaves like a calcium ion analogue that often acts as a regulatory cofactor in a number of important enzymes and receptors [3]. Its unique biological properties have lent themselves to various applications in functional and molecular imaging, most notably in imaging the liver [4], brain function [5], myocardial viability [6], and, more recently, cancer cells [7], [8]. In virtually all applications, the standard protocol is a T 1 -weighted pulse sequence to obtain positive signal contrast in areas of Mn accumulation.…”

Section: Introductionmentioning

confidence: 99%

Ultrashort Echo Time for Improved Positive-Contrast Manganese-Enhanced MRI of Cancer

Nofiele

Cheng

2013

PLoS ONE

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ObjectiveManganese (Mn) is a positive magnetic resonance imaging (MRI) contrast agent that has been used to obtain physiological, biochemical, and molecular biological information. There is great interest to broaden its applications, but a major challenge is to increase detection sensitivity. Another challenge is distinguishing regions of Mn-related signal enhancement from background tissue with inherently similar contrast. To overcome these limitations, this study investigates the use of ultrashort echo time (UTE) and subtraction UTE (SubUTE) imaging for more sensitive and specific determination of Mn accumulation.Materials and MethodsSimulations were performed to investigate the feasibility of UTE and SubUTE for Mn-enhanced MRI and to optimize imaging parameters. Phantoms containing aqueous Mn solutions were imaged on a MRI scanner to validate simulations predictions. Breast cancer cells that are very aggressive (MDA-MB-231 and a more aggressive variant LM2) and a less aggressive cell line (MCF7) were labeled with Mn and imaged on MRI. All imaging was performed on a 3 Tesla scanner and compared UTE and SubUTE against conventional T 1-weighted spoiled gradient echo (SPGR) imaging.ResultsSimulations and phantom imaging demonstrated that UTE and SubUTE provided sustained and linearly increasing positive contrast over a wide range of Mn concentrations, whereas conventional SPGR displayed signal plateau and eventual decrease. Higher flip angles are optimal for imaging higher Mn concentrations. Breast cancer cell imaging demonstrated that UTE and SubUTE provided high sensitivity, with SubUTE providing background suppression for improved specificity and eliminating the need for a pre-contrast baseline image. The SubUTE sequence allowed the best distinction of aggressive breast cancer cells.ConclusionsUTE and SubUTE allow more sensitive and specific positive-contrast detection of Mn enhancement. This imaging capability can potentially open many new doors for Mn-enhanced MRI in vascular, cellular, and molecular imaging.

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“…Mn 2þ as a positive contrast agent in T 1 W MRI has long been used in many biologic applications for brain mapping (26), brain disease (12) (27), neuronal tract tracing (28), and cardiac functional studies (29). Although several factors influencing Mn 2þ uptake in cells have been reported such as voltage-gated Ca 2þ -channel activities (30)(31)(32)(33), NMDA (14) and calcium-sensing receptor (34) expression, astroglia (27) and microglia (35) activity/cellularity, activities of enzymes (e.g., manganese superoxide dismutase; refs. 36, 37) and metal transporters, the mechanisms involved in Mn 2þ uptake in tumor cells are not well known.…”

Section: Discussionmentioning

confidence: 99%

Manganese-Enhanced MRI Reveals Early-Phase Radiation-Induced Cell Alterations In Vivo

et al. 2013

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In vivo imaging of human breast cancer mouse model with high level expression of calcium sensing receptor at 3T

Cited by 10 publications

References 47 publications

In vivo MEMRI characterization of brain metastases using a 3D Look-Locker T1-mapping sequence

In vivo MEMRI characterization of brain metastases using a 3D Look-Locker T1-mapping sequence

Ultrashort Echo Time for Improved Positive-Contrast Manganese-Enhanced MRI of Cancer

Manganese-Enhanced MRI Reveals Early-Phase Radiation-Induced Cell Alterations In Vivo

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