Evaluation of Iron Oxide Nanoparticles for Lymph Node Detection with Magnetomotive Ultrasound- A Pilot Study in Rats

Abstract

IntroductionThe inadequate detection of lymph node metastases by current imaging methods has led to overtreatment in rectal cancer. Magnetomotive ultrasound (MMUS) has the potential of being a more accurate diagnostic imaging method for lymph node metastases. This method is based on the detection of tissue movement that is induced by the vibration of iron oxide nanoparticles, caused by an external alternating magnetic field. This study investigated the suitability of the subcutaneous administration of two iron oxide nanoparticles--Ferrotran(R) and Magtrace(R)--and their distribution in lymph nodes, with regard to the possibility of identifying lymph node metastases in rectal cancer by MMUS. MethodsMale Sprague Dawley rats were injected subcutaneously with 10.7 mg Ferrotran(R) (n=9), 10.5 mg Magtrace(R) (n=9), or saline (n=3) dorsally at the root of the tail. On euthanization of the rats after 1, 5, and 24 hours, the proximal and distal lymph nodes were harvested and analyzed by histology [hematoxylin/eosin, Perls Prussian Blue (PPB)] and inductively coupled plasma-optical emission spectroscopy. The primary aim was to evaluate the distribution of the iron oxide nanoparticles throughout the lymphatic system; the general health of the rats after subcutaneous administration of these nanoparticles was also monitored. ResultsAt 1 hour after subcutaneous injection, Ferrotran(R) and Magtrace(R) accumulated in the proximal lymph nodes. After 24 hours, both particles had spread to distal lymph nodes, but only Ferrotran(R) reached the mesenteric and mandibular lymph nodes. In addition, Ferrotran(R) penetrated the lymph nodes more deeply than Magtrace(R) at 24 hours. No toxicity was observed with either nanoparticle. ConclusionAlthough both compounds disseminated well, Ferrotran(R) accumulated better and more rapidly in lymph nodes than Magtrace(R). Because accumulation and time are important parameters for imaging, our data indicate that Ferrotran(R) is a potentially more suitable particle for MMUS in clinical use.