In Vivo Manganese MR Imaging of Calcium Influx in Spontaneous Rat Pituitary Adenoma

Cross, Donna; Flexman, Jennifer A.; Anzai, Yoshimi; Sasaki, Takahiro; Treuting, Piper M.; Maravilla, K R; Minoshima, Shinsei

doi:10.3174/ajnr.a0693

Cited by 26 publications

(21 citation statements)

References 34 publications

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“…Free Mn 2+ ion is known to accumulate in tumors in vivo [25], [26], [27], [28], [29]. Previously, using MEMRI in a nude rat model, we demonstrated significant Mn 2+ uptake by C918 uveal melanoma xenografts relative to surrounding tissues and speculated that the tumor-specific Mn 2+ uptake may have been a result of high proliferation rates within the tumor [30].…”

Section: Introductionmentioning

confidence: 90%

Human Tumor Cell Proliferation Evaluated Using Manganese-Enhanced MRI

et al. 2012

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BackgroundTumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn2+ [measured with manganese-enhanced MRI (MEMRI)], is linked to proliferation rate in vitro.Methodology/Principal FindingsProliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl2 for one hour and then thoroughly washed. MEMRI R1 values (longitudinal relaxation rates), which have a positive linear relationship with Mn2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn2+-induced increases in R1 compared to cells not exposed to Mn2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R1 values and proliferation rate (p≤0.005), while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet.Conclusions/SignificanceThese data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.

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Section: Introductionmentioning

confidence: 90%

Human Tumor Cell Proliferation Evaluated Using Manganese-Enhanced MRI

et al. 2012

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“…First, it enters cells over several hours and leaves slowly (days to weeks depending on the tissue) so interpretation is not confounded by efflux or time concerns (Tofts et al, 2010). Second, activitydependent manganese entry into cells occurs primarily via LTCCs (Berkowitz et al, 2007b(Berkowitz et al, , 2009a(Berkowitz et al, , 2012aCarlson et al, 1994;Cross et al, 2007;Drapeau and Nachshen, 1984). Importantly, based on the absence of toxicity effects at the present dose of manganese, there is little evidence to suggest that manganese blocks the calcium channels and prevents calcium entry (for more detail see section 9) .…”

Section: Brief History Of Memrimentioning

confidence: 98%

“…In 1997, Alan Koretsky and his group demonstrated the potential value of using a non-toxic dose of the paramagnetic ion manganese as an intracellular MRI contrast agent whose accumulation occurred primarily in active neurons via voltage-gated LTCCs (Berkowitz et al, 2007b(Berkowitz et al, , 2009a(Berkowitz et al, , 2012aCarlson et al, 1994;Cross et al, 2007;Drapeau and Nachshen, 1984;Jacob, 1990;Lin and Koretsky, 1997;Tofts et al, 2010). LTCCs play essential roles modulating neuronal activity including neurotransmitter release, and have a privileged role in activity-dependent gene expression via the transcription factor cAMP response elementbinding protein (Mermelstein et al, 2000;Schmitz and Witkovsky, 1997).…”

Section: Brief History Of Memrimentioning

confidence: 98%

MRI of rod cell compartment-specific function in disease and treatment in vivo

Berkowitz

Bissig

Roberts

2016

Progress in Retinal and Eye Research

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Rod cell oxidative stress is a major pathogenic factor in retinal disease, such as diabetic retinopathy (DR) and retinitis pigmentosa (RP). Personalized, non-destructive, and targeted treatment for these diseases remains elusive since current imaging methods cannot analytically measure treatment efficacy against rod cell compartment-specific oxidative stress in vivo. Over the last decade, novel MRI-based approaches that address this technology gap have been developed. This review summarizes progress in the development of MRI since 2006 that enables earlier evaluation of the impact of disease on rod cell compartment-specific function and the efficacy of anti-oxidant treatment than is currently possible with other methods. Most of the new assays of rod cell compartment-specific function are based on endogenous contrast mechanisms, and this is expected to facilitate their translation into patients with DR and RP, and other oxidative stress-based retinal diseases.

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“…infusion of MnCl 2 . Manganese uptake in the pituitary gland of normal rats is inhibited by Ca 2+ channel blockers, showing dose-dependent inhibition by MRI (Cross et al, 2007). Therefore, Mn 2+ ions are able to substitute for Ca 2+ ions and act as a surrogate marker for neuronal activation within this region (Kuo et al, 2006;Kuo et al, 2005).…”

Section: Discussionmentioning

confidence: 98%