MR Imaging Enables Measurement of Therapeutic Nanoparticle Uptake in Rat N1-S1 Liver Tumors after Nanoablation

作者:McDevitt Joseph L; Mouli Samdeep K; Tyler Patrick D; Li Weiguo; Nicolai Jodi; Procissi Daniele; Ragin Ann B; Wang Y Andrew; Lewandowski Robert J; Salem Riad; Larson Andrew C; Omary Reed A*
来源:Journal of Vascular and Interventional Radiology, 2014, 25(8): 1288-1294.
DOI:10.1016/j.jvir.2014.03.033

摘要

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. NI-Si 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-mu s pulse duration) was applied. Imaging of rats was performed to determine tumor R2* values after the procedure, and change in R2* (Delta R2*) 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 Delta R2* for each subject were assessed for correlation with linear regression, and mean [Fe] for each dosage group was compared with analysis of variance. Results: Delta R2* 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.