Combined Magnetomotive ultrasound, PET/CT, and MR imaging of 68Ga-labelled superparamagnetic iron oxide nanoparticles in rat sentinel lymph nodes in vivo

Abstract

Current methods for intra-surgical guidance to localize metastases at cancer surgery are based on radioactive tracers that cause logistical challenges. We propose the use of a novel ultrasound-based method, magnetomotive ultrasound (MMUS) imaging that employ a nanoparticle-based contrast agent that also may be used for pre-operative PET/MRI imaging. Since MMUS is radiation free, this eliminates the dependence between pre- and intra-operative imaging and the radiation exposure for the surgical staff. This study investigates a hypothetical clinical scenario of pre-operative PET imaging, combined with intra-operative MMUS imaging, implemented in a sentinel lymph node (SLN) rat model. At one-hour post injection of 68Ga-labelled magnetic nanoparticles, six animals were imaged with combined PET/CT. After two or four days, the same animals were imaged with MMUS. In addition, ex-vivo MRI was used to evaluate the amount of nanoparticles in each single SLN. All SLNs were detectable by PET. Four out of six SLNs could be detected with MMUS, and for these MMUS and MRI measurements were in close agreement. The MRI measurements revealed that the two SLNs undetectable with MMUS contained the lowest nanoparticle concentrations. This study shows that MMUS can complement standard pre-operative imaging by providing bedside real-time images with high spatial resolution.

Influence of Magnetic Nanoparticles on the Focused Ultrasound Hyperthermia

“…However small amount of magnetic nanoparticles alone is a weak contrast agent to ultrasound imaging. Nanoparticles are too small to backscatter ultrasound at a detectable level [ 45 ]. However, it is possible to use magnetic properties of nanoparticles for molecular imaging by using the motion of these particles when subjected to gradient magnetic field.…”

Contrast-enhanced magnetomotive ultrasound imaging (CE-MMUS) for colorectal cancer staging: Assessment of sensitivity and resolution to detect alterations in tissue stiffness

“…Excitation with a low frequency (4-16 Hz) electromagnet causes the SPIONS to oscillate, creating a low frequency tissue vibration that can be imaged using ultrasound (centre frequency 20-30 MHz). Despite the small amplitude of displacement involved (1-2 µm [4]), filtering for the known frequency of vibration provides a means of overcoming the diffraction limit of conventional ultrasound imaging such that tissues that have taken up SPIONs can be distinguished from their surroundings. Since the amplitude of tissue displacement will be influenced by stiffness, MMUS also has the potential to present diagnostic information.…”

Molecular Imaging with 68Ga Radio-Nanomaterials: Shedding Light on Nanoparticles

“…68 Ga-labeled SPIONs proved to be stable in human serum at 37 • C for 4 h. These SPIONs served as a dual probe for PET/MR imaging of Sentinel Lymph Nodes (SLN), the first node receiving lymphatic drainage from the primary tumor site, in rat models ( Figure 5). Evertsson et al [69] utilized Madru and coworkers' [70] 68 Ga-SPIONs as a contrast agent for magnetomotive ultrasound (MMUS); a novel ultrasound-based method for intra-surgical guidance to localize metastases during cancer surgery. In their study, 68 Ga-SPIONs served as a dual-imaging probe for pre-operative PET/MRI imaging followed by intra-operative MMUS imaging in a SLN rat model.…”

“…On the other hand, radioisotope desorption from nanoparticle surface is still the main drawback. Some examples in the literature have exploited this property to produce 68 Ge/ 68 Ga generators, to radiolabel nanoparticles with 69 Ge as well as to radiolabel iron oxide nanoparticles with several radioisotopes, including 68 Ga [8,[66][67][68][69][70].…”