MR imaging enables measurement of therapeutic nanoparticle uptake in rat N1-S1 liver tumors after nanoablation.
OBJECTIVE
To test the hypothesis that magnetic resonance (MR) imaging can quantify intratumoral superparamagnetic iron oxide (SPIO) nanoparticle uptake after nanoablation.


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.
Department of Radiology, Northwestern University, Chicago, Illinois.
Joseph L
JL
McDevitt
Department of Radiology, Northwestern University, Chicago, Illinois.
Samdeep K
SK
Mouli
Department of Radiology, Northwestern University, Chicago, Illinois.
Patrick D
PD
Tyler
Department of Radiology, Northwestern University, Chicago, Illinois.
Weiguo
W
Li
Department of Radiology, Northwestern University, Chicago, Illinois.
Jodi
J
Nicolai
Department of Radiology, Northwestern University, Chicago, Illinois.
Daniele
D
Procissi
Department of Radiology, Northwestern University, Chicago, Illinois.
Ann B
AB
Ragin
Ocean Nanotech LLC, Springdale, Arizona.
Y Andrew
YA
Wang
Department of Radiology, Northwestern University, Chicago, Illinois; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
Robert J
RJ
Lewandowski
Department of Radiology, Northwestern University, Chicago, Illinois; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
Riad
R
Salem
Department of Radiology, Northwestern University, Chicago, Illinois; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois; Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.
Andrew C
AC
Larson
Department of Radiology and Radiological Sciences, Vanderbilt School of Medicine, 1611 21st Avenue South, CCC-1106 MCN, Nashville, TN 37232. Electronic address: reed.omary@vanderbilt.edu.
Reed A
RA
Omary
D055011:Ablation Techniques; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers; D053672:Electrochemotherapy; D052203:Ferrosoferric Oxide / Q000737:chemistry / Q000378:metabolism*; D007275:Injections, Intravenous; D016014:Linear Models; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D013058:Mass Spectrometry; D050997:Nanomedicine / Q000379:methods*; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D004317:Doxorubicin; D052203:Ferrosoferric Oxide