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

• Published in: Journal of vascular and interventional radiology Vol. 25; no. 8; pp. 1288 - 1294
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2014
• Subjects: 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; Radiology; Rats, Sprague-Dawley; Time Factors; SPIO; IO; ΔR2; HCC; ICP-MS; DOX; Fe; inductively coupled plasma mass spectrometry; change in R2; iron oxide; superparamagnetic iron oxide; iron; doxorubicin hydrochloride; hepatocellular carcinoma
• ISSN: 1051-0443; 1535-7732; 1535-7732
• DOI: 10.1016/j.jvir.2014.03.033

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