title: Detection of experimental myocardium infarction in rats by MRI using heat shock protein 70 conjugated superparamagnetic iron oxide nanoparticle.
abstract: Superparamagnetic iron-oxide based contrast agents can provide important diagnostic information regarding the assessment of cardiac inflammatory diseases. The aim of the study was to analyze whether nanoparticles conjugated to recombinant 70-kDa heat shock protein (Hsp70-SPION) can be applied for the detection of acute myocardium infarct by MRI. Cellular experiments demonstrated increased CD40-mediated uptake of Hsp70-SPIONs in comparison to non-conjugated SPIONs. Following induction of an acute infarct in rats by ligation of the left anterior descending artery SPIONs and Hsp70-SPION conjugates were injected intravenously on day 4. The animals underwent sequential MRI that showed the presence of the particles in the infarcted zone. Subsequent biodistribution analyses with the help of method on non-linear magnetic response indicated the preferential accumulation of the Hsp70-SPIONs in the heart tissue that was further confirmed with histological analyses. The study demonstrated that an acute infarct can be visualized by MRI using Hsp70-functionalized SPION conjugates.
  
  
  BACKGROUND
  Superparamagnetic iron oxides nanoparticles (SPIONs) have been studied extensively as a contrast agent for MRI. Their tissue specificity can be further enhanced by conjugation with various ligands. In this study, the authors conjugated superparamagnetic nanoparticles to 70-kDa heat shock protein (Hsp70-SPION) to investigate the feasibility for the detection of acute myocardium infarct. The positive findings would suggest that this approach might be used clinically in the future.
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), St. Petersburg, Russia; A.L. Polenov Russian Research Scientific Institute of Neurosurgery, St. Petersburg, Russia; Technische Universität München, Klinikum rechts der Isar, Radiation Oncology, Munich, Germany. Electronic address: shevtsov-max@mail.ru.
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Shevtsov
authors.affiliation: Research Institute of Highly Pure Biopreparations, St. Petersburg, Russia.
authors.forename: Boris P
authors.initials: BP
authors.lastname: Nikolaev
authors.affiliation: National Research Centre "Kurchatov Institute" B.P. Konstantinov Petersburg Nuclear Physics Institute, Gatchina, Russia.
authors.forename: Vyacheslav A
authors.initials: VA
authors.lastname: Ryzhov
authors.affiliation: Research Institute of Highly Pure Biopreparations, St. Petersburg, Russia.
authors.forename: Ludmila Y
authors.initials: LY
authors.lastname: Yakovleva
authors.affiliation: Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), St. Petersburg, Russia.
authors.forename: Anatolii V
authors.initials: AV
authors.lastname: Dobrodumov
authors.affiliation: Research Institute of Highly Pure Biopreparations, St. Petersburg, Russia.
authors.forename: Yaroslav Y
authors.initials: YY
authors.lastname: Marchenko
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), St. Petersburg, Russia.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Margulis
authors.affiliation: The Wharton School, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Emil
authors.initials: E
authors.lastname: Pitkin
authors.affiliation: I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS), St. Petersburg, Russia.
authors.forename: Anastasiy L
authors.initials: AL
authors.lastname: Mikhrina
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), St. Petersburg, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Guzhova
authors.affiliation: Technische Universität München, Klinikum rechts der Isar, Radiation Oncology, Munich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D005290:Ferric Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000032:analysis / Q000737:chemistry*; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging*; D009206:Myocardium / Q000473:pathology; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D018840:HSP70 Heat-Shock Proteins; D058185:Magnetite Nanoparticles; C000499:ferric oxide
keywords: CD40; Hsp70; Magnetic resonance imaging; Myocardial infarction; Superparamagnetic nanoparticles