Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI

SIMPLE SUMMARY: Magnetic resonance imaging (MRI) is a non-invasive method and can be used to diagnose prostate cancer (PCa). Due to their high biological safety, iron oxide nanoparticles are becoming increasingly important as contrast agents for MRI. Macrophages are able to take up these iron particles, which leads to a loss of signal in T2- and T2*-weighted images during MRI. Macrophages play an important role in the development and progression of prostate cancer. In this article, ferumoxytol is visualized at two different PCa volumes on MRI in a xenograft mouse model. Ferumoxytol is a superparamagnetic iron oxide probe and was used here as a contrast agent. The in vivo data were correlated with histological data. When using ferumoxytol, we found that small tumors took up more ferumoxytol than larger tumor volumes. These results were obtained in vivo as well as ex vivo. ABSTRACT: Prostate cancer (PCa) is one of the most common cancers in men. For detection and diagnosis of PCa, non-invasive methods, including magnetic resonance imaging (MRI), can reduce the risk potential of surgical intervention. To explore the molecular characteristics of the tumor, we investigated the applicability of ferumoxytol in PCa in a xenograft mouse model in two different tumor volumes, 500 mm(3) and 1000 mm(3). Macrophages play a key role in tumor progression, and they are able to internalize iron-oxide particles, such as ferumoxytol. When evaluating T2*-weighted sequences on MRI, a significant decrease of signal intensity between pre- and post-contrast images for each tumor volume (n = 14; p < 0.001) was measured. We, furthermore, observed a higher signal loss for a tumor volume of 500 mm(3) than for 1000 mm(3). These findings were confirmed by histological examinations and laser ablation inductively coupled plasma-mass spectrometry. The 500 mm(3) tumors had 1.5% iron content (n = 14; σ = 1.1), while the 1000 mm(3) tumors contained only 0.4% iron (n = 14; σ = 0.2). In vivo MRI data demonstrated a correlation with the ex vivo data (R(2) = 0.75). The results of elemental analysis by inductively coupled plasma-mass spectrometry correlated strongly with the MRI data (R(2) = 0.83) (n = 4). Due to its long retention time in the blood, biodegradability, and low toxicity to patients, ferumoxytol has great potential as a contrast agent for visualization PCa.