Bringing molecular specificity to MRI could change the way cancer is diagnosed. We’re proud of the first-of-its-kind technology behind MagSense®, but breakthrough technology alone does not guarantee success. It also has to make sense for the businesses and clinicians around it.
In this three-part series, 10 Things to Know About MagSense, we break down the fundamentals essential to understanding the key factors that could drive the MagSense technology to clinical and commercial success. Whether you’re an investor, a prospective strategic partner, member of the medical community or an individual seeking to understand our technology better, we hope you find it useful.
This first installment focuses on market fit, exploring how MRI manufacturers, contrast media companies and radiopharmaceutical developers each stand to benefit from MagSense.
MRI Manufacturers Will Likely Embrace MagSense
MRI has long been the gold standard of medical imaging, providing exquisite tissue contrast and the ability to detect subtle changes in anatomy. However, despite this high sensitivity, MRI still lacks the ability to concretely determine if an abnormality is actually cancer, or if it may be a mimic or other benign artifact. The holy grail for MRI has been to introduce molecular specificity, meaning that a high-confidence diagnosis could be made from imaging alone. As such, MRI manufacturers are fighting a two-front battle to gain market share in cancer diagnosis. Cheaper, faster alternatives such as CT and Ultrasound, while not providing the image quality or diagnostic value of MRI, are gaining share as hospitals become increasingly cost and workflow conscious. Similarly, PET imaging, which relies on molecularly targeted radiotracers, is gaining adoption due to its higher specificity. This is despite the fact that PET is multiples more expensive than MRI, requires special handling through nuclear pharmacies and exposes patients to harmful radiation (more on PET imaging later). Molecular MRI such as MagsSense offers MRI manufacturers access to a tool that is highly sensitive and specific, but without the cost, workflow constraints and radiation exposure of PET.
A review of the current state of advanced MRI highlights this problem. Over the last few decades there have been tremendous improvements in imaging hardware and software. Techniques like multiparametric MRI (mpMRI) and biparametric MRI (bpMRI) combine functional MRI (fMRI) with conventional MRI to try to better characterize suspicious lesions. For example, mpMRI uses a combination of three imaging methods – standard T2-weighted imaging for anatomical information, diffusion weighted imaging (DWI) for improved assessment of water content, and dynamic contrast enhanced (DCE) imaging for assessing blood flow. Because cancers are typically denser than healthy tissue, a DWI image assesses the density of a suspicious lesion while the DCE image looks for abnormal blood flow that is typically associated with cancers. But these techniques are still an indirect assessment of the tissue, and studies continue to report high false positive and false negative results even with advanced techniques like mpMRI. As a result, medical imaging is used as an “aid in the diagnosis” because it can’t truly confirm if the tissue being imaged is cancer. From a clinical care perspective, this means more complicated and costly MRI procedures are being applied without necessarily improving the diagnostic utility of MRI. But, by combining the molecular targeting of the MagSense imaging agent with the high resolution and quantitative imaging techniques available on today’s MRI systems, we might expect to achieve better positive and negative predictive outcomes.
Better outcomes from mMRI would increase demand and usage of MRI systems and transform the value proposition for the MRI manufacturers.
Contrast Media Companies Need Innovation
MRI contrast media companies are facing a challenge. Currently, the product portfolios of these companies are largely driven by Gadolinium-Based Contrast Agents (GBCAs), which, after decades on the market, are facing increased competition and lower margins. As a result, R&D pipelines are generating consistently diminishing returns. In order to gain market share and increase profitability, GBCA manufacturers need to find new products that add value and can be sold within their already established MRI sales channels.
The first GBCAs were introduced in 1988. These compounds are made of small paramagnetic metal chelates that produce a brightening of an MRI scan, hence the term “contrast enhanced MRI” (CE-MRI). When administered intravenously, GBCAs circulate with the blood and improve the visibility of arterial blood flow. The use of GBCAs for blood-based imaging is by far the lion’s share of the GBCA business. But because of their small size, GBCAs also perfuse into the intravascular and extracellular fluid spaces where the chelated metal interacts with the adjacent water molecules in tissue. But like the new MRI techniques described above, this use of GBCAs provides an indirect assessment of the tissue. They might increase the visibility and definition of a lesion, but they still don’t reveal any molecular basis of the tissue.
Adding molecular specificity to GBCAs will be more than a little challenging for contrast media companies – it’s a matter of physics. That’s because gadolinium has a relatively low magnetic relaxivity (5-80 (mMs)-1) compared to the iron oxide (200-300 (mMs)-1) in our MagSense agents. If you try to attach a gadolinium molecule to a targeting ligand, like an antibody, it doesn’t have sufficient relaxivity to affect the image. You’d have to find a way to bundle a bunch of gadolinium molecules to the target ligand to get a sufficient change in MRI signal. That would make the chemistry and manufacturability complicated. Furthermore, GBCAs have come under regulatory restrictions due to toxicity concerns, both nephrotoxicity (kidney) and neurotoxicity (brain). While improvements have been made in the design of GBCA compounds to address the toxicity concerns, the use of metal chelates for imaging is likely to continue to face regulatory headwinds.
MagSense technology solves the technical challenges of adding molecular specificity to an imaging agent and eliminates the toxicity concerns because the iron particles can be administered in low concentrations and are metabolized in the liver where the iron is repurposed to ferritin. Additionally, a portfolio of imaging agents for oncology applications would be additive to and not competing with the use of GBCAs for vascular and general-purpose imaging.
For companies in the contrast media space, our MagSense technology offers an innovation (molecular specificity) that can’t easily be replicated with what’s in their current portfolios.
MagSense® is Complementary to Radiopharmaceuticals
Radiopharmaceuticals have evolved significantly since their first introduction, from starting primarily as diagnostic agents to now including targeted therapeutic applications. While this evolution has expanded the market size for radiopharmaceuticals, the technology still faces several barriers to widespread adoption and growth: poor image resolution, high costs of both development and deployment, specialized workflow and handling considerations, and safety concerns regarding radiation exposure. MagSense could alleviate these concerns, becoming an ideal complement to radiopharmaceutical therapies.
Today, the primary business model of radiopharmaceutical companies is the development of therapies employing radioisotopes for the treatment of disease – i.e. a radiopharmaceutical. To minimize the exposure of the radiation, the radioisotopes are often paired with a targeting molecule to deliver the radiation directly to the diseased tissue.
However, monitoring treatment efficacy requires both confirmation that the therapeutic is reaching its intended target and that subsequently the tumor is responding to the treatment. To do this, the targeting molecules used to deliver the radiation for treatment can be paired with a different radioisotope as a “radiotracer” that is detectable by Positron Emission Tomography (PET). This is best exemplified by the recent introduction of PSMA-PET. By pairing the Prostate Specific Membrane Antigen (PSMA) to a radiotracer, an imaging-based companion diagnostic market has begun to emerge.
PET imaging has virtually no background noise and is a very sensitive detection method. This makes it a good technique for finding small or distant metastases. But PET imaging has poor resolution. This combination of high sensitivity but poor resolution has, thus far, limited the diagnostic utility of PET imaging. To overcome the problem of poor resolution, PET scans can be paired with another imaging modality such as CT or SPECT, to provide clinically useful context. But in doing so, they increase the overall cost for the diagnostic procedure and expose the patient to further radiation.
While there has been significant growth in the use of PET imaging over the past several years, there are commercial and clinical challenges that are likely to hamper the global adoption of radiotracers for imaging. Because PET tracers use short half-life radioisotopes, the PET tracer must be made at a nearby cyclotron and administered to the patient immediately after. This limits the market based on the cost and availability of the required infrastructure to support PET imaging. Additionally, the use of PET tracers exposes both patients and clinical staff to radiation. Given these limitations, and the hazards associated with use of radioactivity, the clinical utility of PET imaging is not likely to go mainstream for primary diagnostic imaging purposes.
MagSense offers a potential solution to this problem, as any targeting molecule that can be used for PET imaging can also be used for mMRI with MagSense. While PET imaging is good at detecting distant metastases, MagSense, paired with the high resolution and clarity of MRI, may be a superior tool for primary tumor diagnosis and therapeutic monitoring. Additionally, MagSense imaging agents, as you’ll learn in the next installment, don’t have the same clinical, commercial or safety limitations as PET tracers. MagSense uses existing MRI infrastructure, can be stored and distributed through standard hospital pharmacies and achieves the imaging objective without any exposure to radiation. Thus, MagSense potentially offers a superior primary diagnostic tool to support the use of radiopharmaceutical therapies.
MagSense imaging would be complementary to the radiopharmaceutical industry, offering a safer, more ubiquitous companion diagnostic imaging method for the market.
What This Means for the Imaging Ecosystem
For MRI manufacturers, MagSense offers a path to greater clinical value. For contrast media companies, it brings an innovation their current portfolios can’t easily replicate. And for radiopharmaceutical developers, it opens a complementary route to molecular imaging without the limits of PET. Together, these points show how MagSense is positioned to strengthen the imaging market rather than compete with it.
In our next release of the 10 Things to Know About MagSense series, we’ll turn to commercial readiness, looking at the size of the market, how MagSense fits existing clinical supply chains and why its health economics and pricing could make it attractive for providers.
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