T1 and t2 of ferritin at different field strengths: effect on mri

Vymazal, Josef; Brooks, Rodney A.; Zak, Olga; McRill, C; Shen, Chuanan; Chiro, Giovanni Di

doi:10.1002/mrm.1910270218

Cited by 106 publications

(85 citation statements)

References 20 publications

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“…An advantage of using MRI reporter genes to introduce contrast agents is that longterm imaging is possible and the negative side effects of exogenous MR contrast agents are avoided. Ferritin, the ironstoring protein of mammals, can store up to 4,500 iron and has been accepted as a universal MRI reporter gene (7)(8)(9)(10)(11)(12)30). The presence of ferritin in organs influences the contrast of T 2 -weighted MRI at very low iron concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the ferritin gene has been used as an iron-accumulating reporter gene for evaluating the efficacy of gene and cell therapy by MRI (7)(8)(9)(10)(11)(12). Ferritin is an iron storage protein that can be ectopically expressed to augment endogenous iron uptake and produce signal changes in the surrounding environment that can be detected by MRI.…”

Section: Introductionmentioning

confidence: 99%

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In vivo Imaging of Tumor Transduced with Bimodal Lentiviral Vector Encoding Human Ferritin and Green Fluorescent Protein on a 1.5T Clinical Magnetic Resonance Scanner

et al. 2010

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A combination of reporter genes for magnetic resonance imaging (MRI) and optical imaging can provide an additional level of noninvasive and quantitative information about biological processes occurring in deep tissues. We developed a bimodal lentiviral vector to monitor deep tissue events using MRI to detect myc-tagged human ferritin heavy chain (myc-hFTH) expression and fluorescence imaging to detect green fluorescent protein (GFP) expression. The transgene construct was stably transfected into MCF-7 and F-98 cells. After transplantation of the cells expressing myc-hFTH and GFP into mice or rats, serial MRI and fluorescence imaging were performed with a human wrist coil on a 1.5T MR scanner and optical imaging analyzer for 4 weeks. No cellular toxicity due to overexpression of myc-hFTH and GFP was observed in MTT and trypan blue exclusion assays. Iron accumulation was observed in myc-hFTH cells and tumors by Prussian blue staining and iron binding assays. The myc-hFTH cells and tumors had significantly lower signal intensities in T 2 -weighted MRI than mock-transfected controls (P ≤ 0.05). This is direct evidence that myc-hFTH expression can be visualized noninvasively with a 1.5T clinical MR scanner. This study shows that MRI and fluorescence imaging of transplanted cells at molecular and cellular levels can be performed simultaneously using our bimodal lentiviral vector system. Our techniques can be used to monitor tumor growth, metastasis, and regression during cell and gene-based therapy in deep tissues. Cancer Res; 70(18); 7315-24. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivo Imaging of Tumor Transduced with Bimodal Lentiviral Vector Encoding Human Ferritin and Green Fluorescent Protein on a 1.5T Clinical Magnetic Resonance Scanner

et al. 2010

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“…The iron detection threshold at 1.5 T was established by Aoki et al (32) and quantified as 10 -15 mg/100 g. This does not, however, allow us to quantitatively determine the iron level with T 2 or T 2 *-weighted MRI since other factors also affect these parameters. It is known that the sensitivity of MRI to iron increases with magnetic field strength, since the T 2 signal is linearly dependent on the magnetic field strength (33). However, this relationship has never been investigated at strengths higher than 3 T (34) and, therefore, we cannot quantify the amount of iron in the thalamus.…”

Section: Iron and Amyloidmentioning

confidence: 96%

Noninvasive in vivo MRI detection of neuritic plaques associated with iron in APP[V717I] transgenic mice, a model for Alzheimer's disease

Vanhoutte¹,

Dewachter

Borghgraef

et al. 2005

Magnetic Resonance in Med

127

109

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Alzheimer's disease (AD) is characterized by a progressive decline of cognitive function, while the neuropathologic features include the occurrence of neurofibrillary tangles, neuritic plaques, decreased synaptic density, and loss of neurons. Neuritic plaques consist of extracellular ␤-amyloid (A␤) deposits surrounded by dystrophic neuritis (1). The plaques are neurotoxic and induce inflammatory responses. According to the amyloid cascade hypothesis, the increased amyloid deposition results in the onset and progression of AD (2,3,4,5) and therefore amyloid plaques became crucial as a target for many therapeutic approaches (6,7).Despite the impact of in vivo imaging techniques in daily clinical practice and also in neuroscience, typical Alzheimer plaques were never visualized in vivo in patients. To diagnose AD and to differentiate from other dementias, the detection of at least one typical hallmark, i.e., amyloid plaques or neurofibrillary tangles, appears essential. To date, accumulations of amyloid in AD patients have been observed only postmortem. Recently, however, significant progress has been made visualizing AD plaques using transgenic mouse models for AD. Skovronsky et al. (8) reported in vivo labeling of amyloid plaques in transgenic mice using a radiolabeled ligand but detection was still performed postmortem with fluorescence microscopy. Another attempt to demonstrate plaques postmortem used MRI and was based on injection of a specific derivative of the amyloid peptide with a high molecular specificity for amyloid as a label, i.e., putrescine-gadolinium-A␤ (9). Finally, Wadghiri et al. (10) used systemic injection of monocrystalline iron oxide nanoparticles or gadolinium (Gd) labeled A␤ 1-40 peptide with a high affinity for A␤ and were able to detect ex vivo but also in vivo amyloid plaques in the affected mouse brains. In this approach, the main obstacle for amyloid labeling remains the blood brain barrier and its transient opening using mannitol must be considered quite invasive. Another drawback may be the authentication of amyloid plaques and the exclusion of the involvement of blood vessels embedded with contrast agent, which requires subsequent histology of the brain.The first MRI study that demonstrated amyloid plaques without any exogenous labeling was performed by Benveniste et al. in 1999 (11). Three dimensional T 2 * images of postmortem human AD brain samples, acquired in more than 2.7 hr, revealed dark spots in the brain correlating with histologic amyloid staining. Recently, using T 2 MR contrast, identification of plaque-like structures in the cortex and hippocampus of fixed mouse brain was reported by Zhang et al. (12). However, the authors did not explain the source of the MR contrast in relation to the physiologic processes related with plaque formation and the evidence was only confirmed by the subsequent co registration of plaques by histology. Analogous to this finding, Helpern et al. (13) demonstrated a reduced T 2 value in the cortex and hippocampus in vivo in an AD mouse model,...

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“…Because 1/T 2 in ferritin solution increases linearly withˆeld strength, the use of MR imaging scanners with ever higher magneticˆelds is of particular interest. 57 Koretsky's group has also proposed that aggregation of ferritin by binding to cytoskeletal elements may increase 1/T 2 , which would be a way to improve sensitivity. 58 So far, most eŠorts in in vivo reporter gene MR imaging have centered on animal studies to providè`p roof-of-principle'' evidence, and there is little information on clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

Molecular MR Imaging of Cancer Gene Therapy: Ferritin Transgene Reporter Takes the Stage

2010

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Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic e‹cacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation-mediated cancer gene therapy using the ferritin reporter gene.

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T1 and t2 of ferritin at different field strengths: effect on mri

Cited by 106 publications

References 20 publications

In vivo Imaging of Tumor Transduced with Bimodal Lentiviral Vector Encoding Human Ferritin and Green Fluorescent Protein on a 1.5T Clinical Magnetic Resonance Scanner

In vivo Imaging of Tumor Transduced with Bimodal Lentiviral Vector Encoding Human Ferritin and Green Fluorescent Protein on a 1.5T Clinical Magnetic Resonance Scanner

Noninvasive in vivo MRI detection of neuritic plaques associated with iron in APP[V717I] transgenic mice, a model for Alzheimer's disease

Molecular MR Imaging of Cancer Gene Therapy: Ferritin Transgene Reporter Takes the Stage

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