Functionalized magnetonanoparticles for MRI diagnosis and localization in epilepsy

Jane & Terry Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Epilepsia (Impact Factor: 4.57). 06/2008; 49(8):1419-30. DOI: 10.1111/j.1528-1167.2008.01615.x
Source: PubMed


The development of nonradioactive and targeted magnetonanoparticles (MNP) capable of crossing the blood-brain barrier (BBB) and of concentrating in the epileptogenic tissues of acute and chronic animal models of temporal lobe epilepsy to render these tissues visible on magnetic resonance imaging (MRI).
Nonradioactive alpha methyl tryptophan (AMT) was covalently attached to MNP composed of iron oxide and dextran. A rodent model of temporal lobe epilepsy was prepared by injecting kainic acid into the right hippocampus. AMT-MNP or plain MNP was injected in the tail-vein of two animals during the acute stage 3 days after status epilepticus, and AMT-MNP in five animals during the chronic stage. MRIs were obtained before and after particle injection in all animals. Intracranial EEGs were obtained in all chronic animals after completion of MRI studies.
AMT-MNP crossed the BBB and intraparenchymal uptake was visible on MRI. In the acute condition, AMT-MNP appeared to localize to both hippocampi, whereas plain MNP only identified unilateral, presumably inflammatory, changes. In the chronic condition, AMT-MNP uptake correlated with the occurrence of spontaneous seizures, and the location of uptake appeared to agree with bilateral or unilateral epileptogenicity confirmed by subsequent intracranial EEG.
Nonradioactive AMT-MNP can cross the BBB and may accurately localize epileptogenic cerebral regions. The MNP-MRI approach is potentially applicable to the use of any bioactive molecules as ligands for imaging normal and abnormal localized cerebral functions, accurately, safely, and inexpensively.

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    • "Functionalized MNPs consisting of a paramagnetic iron oxide core surrounded by a dextran coating were developed and conjugated with alpha-methyl-tryptophan (AMT), a putative surrogate marker of epileptogenic tissue (Akhtari et al., 2008). These particles were given intravenously to rats injected intrahippocampally with kainic acid, immediately after status epilepticus, and weeks to months later. "
    Epilepsia 02/2010; 51 Suppl 1(s1):83-6. DOI:10.1111/j.1528-1167.2009.02456.x · 4.57 Impact Factor
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    • "AMT is preferentially taken up in epileptogenic foci and reflects increased serotonin production or induction of the kynurenine pathway (Juhasz et al, 2004). In acute studies, AMT USPIOs injected 3 days after kainic acid-induced status epilepticus localized to bilateral hippocampi, whereas plain USPIOs were only observed unilateral to the lesion, presumably because of inflammation (Akhtari et al, 2008). In chronic studies, the authors correlated AMT USPIO uptake with the occurrence of spontaneous seizures; MRI-localization of the USPIOs agreed with electroencephalography. "
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    ABSTRACT: Superparamagnetic iron oxide nanoparticles have diverse diagnostic and potential therapeutic applications in the central nervous system (CNS). They are useful as magnetic resonance imaging (MRI) contrast agents to evaluate: areas of blood-brain barrier (BBB) dysfunction related to tumors and other neuroinflammatory pathologies, the cerebrovasculature using perfusion-weighted MRI sequences, and in vivo cellular tracking in CNS disease or injury. Novel, targeted, nanoparticle synthesis strategies will allow for a rapidly expanding range of applications in patients with brain tumors, cerebral ischemia or stroke, carotid atherosclerosis, multiple sclerosis, traumatic brain injury, and epilepsy. These strategies may ultimately improve disease detection, therapeutic monitoring, and treatment efficacy especially in the context of antiangiogenic chemotherapy and antiinflammatory medications. The purpose of this review is to outline the current status of superparamagnetic iron oxide nanoparticles in the context of biomedical nanotechnology as they apply to diagnostic MRI and potential therapeutic applications in neurooncology and other CNS inflammatory conditions.
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    • "The last issue considered for this review was that of August 2008. In it, Akhtari et al. (2008) reported the development of nonradioactive and targeted magnetonanoparticles , composed of iron oxide and dextran, capable of crossing the blood–brain barrier and of concentrating in the epileptogenic tissues of acute and chronic animal models of temporal lobe epilepsy to render these tissues visible on MRI. "
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