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 PD, McDevitt JL, Sheu AY, Nicolai J, Procissi D, Ragin AB, Lewandowski RJ, Salem R, Larson AC, Omary RA
Invest Radiol. 2014 49 (2): 87-92

PMID: 24089022 · DOI:10.1097/RLI.0b013e3182a7e1b7

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.

MeSH Terms (14)

Animals Antibiotics, Antineoplastic Dextrans Doxorubicin Humans Liver Neoplasms, Experimental Magnetic Resonance Imaging Magnetite Nanoparticles Male Nanoparticles Rats Rats, Sprague-Dawley Tissue Distribution Treatment Outcome

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