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Seven-Tesla Magnetic Resonance Imaging Accurately Quantifies Intratumoral Uptake of Therapeutic Nanoparticles in the McA Rat Model of Hepatocellular Carcinoma: Preclinical Study in a Rodent Model

Tyler, Patrick D. BA*‡; McDevitt, Joseph L. BA*‡; Sheu, Alexander Y. BS*‡; Nicolai, Jodi MS*; Procissi, Daniele PhD*; Ragin, Ann B. PhD*; Lewandowski, Robert J. MD; Salem, Riad MD; Larson, Andrew C. PhD*†§; Omary, Reed A. MD, MS

doi: 10.1097/RLI.0b013e3182a7e1b7
Original Articles

Objectives After inducing McA tumors in Sprague-Dawley rats (McA-SD), the following hypotheses were tested: first, that hypervascular McA tumors grown in Sprague-Dawley rats provide a suitable platform to investigate drug delivery; and second, that high-field MRI can be used to measure intratumoral uptake of DOX-SPIOs.

Materials and Methods McA cells were implanted into the livers of 18 Sprague-Dawley rats. In successfully inoculated animals, 220-μL DOX-SPIOs were delivered to tumors via the intravenous or intra-arterial route. Pretreatment and posttreatment T2*-weighted images were obtained using 7-T MRI, and change in R2* value (ΔR2*) was obtained from mean signal intensities of tumors in these images. Tumor iron concentration ([Fe]), an indicator of DOX-SPIO uptake, was measured using mass spectroscopy. The primary outcome variable was the Pearson correlation between ΔR2* and [Fe].

Results Tumors grew successfully in 13 of the 18 animals (72%). Mean (SD) maximum tumor diameter was 0.83 (0.25) cm. The results of phantom studies revealed a strong positive correlation between ΔR2* and [Fe], with r = 0.98 (P < 0.01). The results of in vivo drug uptake studies demonstrated a positive correlation between ΔR2* and [Fe], with r = 0.72 (P = 0.0004).

Conclusions The McA tumors grown in the Sprague-Dawley rats demonstrated uptake of nanoparticle-based therapeutic agents. Magnetic resonance imaging quantification of intratumoral uptake strongly correlated with iron concentrations in pathological specimens, suggesting that MRI may be used to quantify uptake of iron-oxide nanotherapeutics.

From the Departments of *Radiology, and †Biomedical Engineering, ‡Feinberg School of Medicine, and §Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; and ∥Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN.

Received for publication April 14, 2013; and accepted for publication, after revision, July 26, 2013.

Conflicts of interest and sources of funding: Supported by research grants NIH R01 CA159178 from the National Institutes of Health, Bethesda, MD (Drs Omary, Larson, and Lewandowski).

Supported by grant no. 3216863 from the American Cancer Society-Illinois Division, Chicago, IL (Dr Lewandowski).

Supported by the SIR Foundation Student Research Grant, Fairfax, VA (Patrick D. Tyler).

The authors report no conflicts of interest.

Presented at the Society of Interventional Radiology Annual Meeting, April 13–18, 2013.

Reprints: Reed A. Omary, MD, MS, Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, 1611 21st Ave S, CCC-1106 MCN, Nashville, TN 37232-2675. E-mail:

© 2014 by Lippincott Williams & Wilkins