Functionalized magnetonanoparticles for MRI diagnosis and localization in epilepsy.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Akhtari
Massoud
M
Jane & Terry Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA. Akhtarim@ucla.edu
Bragin
Anatol
A
Cohen
Mark
M
Moats
Rex
R
Brenker
Frank
F
Lynch
Mattew D
MD
Vinters
Harry V
HV
Engel
Jerome
J
D000208:Acute Disease; D000818:Animals; D001812:Blood-Brain Barrier; D002908:Chronic Disease; D003720:Densitometry; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis*; D005904:Glial Fibrillary Acidic Protein; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D015225:Magnetoencephalography; D053768:Metal Nanoparticles; D051381:Rats; D014364:Tryptophan / Q000031:analogs & derivatives
D005904:Glial Fibrillary Acidic Protein; C028129:tryptophan methyl ester; D014364:Tryptophan