Early detection remains one of the greatest opportunities to increase survival of women with ovarian cancer.
We hypothesize that a novel technology known as nanomagnetic relaxometry could be used to accomplish this task by providing an alternative to transvaginal ultrasound (TVU) as a second-line diagnostic tool in patients with rising levels of cancer antigen 125 (CA125). The MRXII instrument (Senior Scientific LLC, Albuquerque, NM) uses an array of ultra-sensitive superconducting quantum interference devices (SQUIDs) to detect tumor-bound superparamagnetic nanoparticles (NPs). Tumor detection is accomplished by injecting biologically-targeted NPs, applying a brief magnetic pulse, and then detecting the resulting signal with the SQUID sensors.
Nanomagnetic relaxometry is a magnetic detection technology that relies on the use of targeting agents (antibodies) linked to specific proprietary superparamagnetic nanoparticles (PrecisionMRX™; Senior Scientific LLC, Albuquerque, NM). The targeted NPs are injected into a cell culture or mouse model and then a small magnetizing field (50 Gauss) is applied for 0.75 seconds before the field is turned off. The application of a brief magnetic field allows NPs specifically bound to biomarker-expressing cells to be measured using SQUIDs – sensors that are ultrasensitive for detection of low magnetic fields. Only bound NPs are detected by the SQUID sensors because, once the magnetic field is turned off, unbound NPs decay by Brownian motion within less than 1 millisecond, while biomarker‐bound NPs decay at a much slower rate (0.1 to 2 seconds) by the Néel mechanism. The signal detected by the SQUID sensors is then used to determine where the bound NPs were located.
Unlike current second-line ovarian cancer screening methods (e.g., TVU), which are imaging-based and rely on visualization of the shape and other physical properties of the tumor, MRX is similar to a blood test in that it detects the presence of cancer cells (along with their approximate location) using targeted NPs. The advantage of this technology is that it is up to 200 times more sensitive than current imaging technologies (based on unpublished data). In addition to the sensitivity advantages, it is also believed to be unparalleled in terms of specificity. Because the technology relies on NPs binding to specific cancer cells and is detecting molecular markers, only cancer will presumably be detected with this technology. Another advantage of nanomagnetic relaxometry compared to some imaging-based technologies is that it does not expose patients to potentially harmful ionizing radiation and, because this technology is considered to be safe for human use, we expect that human studies could begin within the next five years. Thus, nanomagnetic relaxometry holds promise for detecting ovarian cancer much earlier, which is crucial to increasing survivorship.
Preliminary results indicate that the in vitro detection limits (determined through cell titration studies) of MRX are on the order of 104 ovarian cancer cells. Additionally, the MRX technology has been able to successfully detect ovarian tumors in vivo.
Transmission Electron Microscopy (TEM)
A TEM image of an ovarian cancer cell covered with nanoparticles (Ocean NanoTech, LLC, Springdale, AR), which were incubated with the cells for 30 minutes. These nanoparticles were targeted to the cells using CA125 antibodies and on the order of 106 nanoparticles were bound to each cell. As this photo shows, the nanoparticles were not internalized and remained on the cell surface.