MR imaging enables measurement of therapeutic nanoparticle uptake in rat N1-S1 liver tumors after nanoablation

J Vasc Interv Radiol. 2014 Aug;25(8):1288-94. doi: 10.1016/j.jvir.2014.03.033. Epub 2014 May 20.

Abstract

Purpose: To test the hypothesis that magnetic resonance (MR) imaging can quantify intratumoral superparamagnetic iron oxide (SPIO) nanoparticle uptake after nanoablation.

Materials and methods: SPIO nanoparticles functionalized with doxorubicin were synthesized. N1-S1 hepatomas were successfully induced in 17 Sprague-Dawley rats distributed into three dosage groups. Baseline tumor R2* values (the reciprocal of T2*) were determined using 7-tesla (T) MR imaging. After intravenous injection of SPIO nanoparticles, reversible electroporation (1,300 V/cm, 8 pulses, 100-μs pulse duration) was applied. Imaging of rats was performed to determine tumor R2* values after the procedure, and change in R2* (ΔR2*) was calculated. Inductively coupled plasma mass spectrometry was used to determine intratumoral iron (Fe) concentration after the procedure, which served as a proxy for SPIO nanoparticle uptake. Mean tumor Fe concentration [Fe] and ΔR2* for each subject were assessed for correlation with linear regression, and mean [Fe] for each dosage group was compared with analysis of variance.

Results: ΔR2* significantly correlated with tumor SPIO nanoparticle uptake after nanoablation (r = 0.50, P = .039). On average, each 0.1-ms(-1) increase in R2* corresponded to a 0.1394-mM increase in [Fe]. There was no significant difference in mean SPIO nanoparticle uptake among dosage groups (P = .57).

Conclusions: Intratumoral SPIO nanoparticle uptake after nanoablation can be successfully quantified noninvasively with 7-T MR imaging. Imaging can be used as a method to estimate localized drug delivery after nanoablation.

MeSH terms

  • Ablation Techniques*
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Chemistry, Pharmaceutical
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Doxorubicin / metabolism
  • Drug Carriers*
  • Electrochemotherapy
  • Ferrosoferric Oxide / chemistry
  • Ferrosoferric Oxide / metabolism*
  • Injections, Intravenous
  • Linear Models
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Magnetic Resonance Imaging*
  • Magnetite Nanoparticles*
  • Male
  • Mass Spectrometry
  • Nanomedicine / methods*
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Magnetite Nanoparticles
  • Doxorubicin
  • Ferrosoferric Oxide