Targeting cancers with magnetism

The medical technology company Endomag uses magnetic fields and tiny magnetic particles to evaluate the progression of breast cancer. By developing a magnetic tracer and a detector that can find the tracer in the body, it has created technology that simplifies cancer diagnosis. The first products commercialised from this platform – the Sienna+ tracer and Sentimag detector – make it easier to confirm whether cancer has spread. The company’s first target for its technology was to improve the diagnosis of breast cancer. The medical community is now adopting Sienna+ and Sentimag for other cancers.

Magnetic nanoparticles

Endomag has had to overcome many challenges since 2007, when it span out of research being conducted at University College London and the University of Houston, Texas. One of its first tasks was to develop an instrument that could detect less than a tenth of a milligram of magnetic nanoparticles 3 cm deep in body tissue. Each nanoparticle has a diameter of around 60 nanometres, about one hundredth the size of a red blood cell. The nanoparticles consist of a small 5–10 nm core of superparamagnetic iron oxide, coated with sugar to make the nanoparticles biologically compatible. The particles have similar dimensions to viruses and are naturally filtered out, like foreign invaders, in the lymph nodes.

The original prototype magnetic detector, devised by Simon Hattersley at University College London and Audrius Brazdeikis at the University of Houston, relied on a superconducting quantum interference device sensor that requires cryogenic cooling to operate. Given the requirement for a flask of liquid nitrogen, the early prototypes were not practical or safe for use in an operating theatre. In 2009, Hattersley devised a way of using a room-temperature sensor to achieve similar sensitivity by using exacting tolerances in the probe’s induction coils. This required a novel sensor design alongside a specialised signal processing system and, by 2010, the team had developed the Sentimag – see Sentimag probe.

The Sentimag is the world’s most sensitive handheld sensor of magnetic susceptibility – a measure of the degree to which a material responds to a magnetic field. The challenge in developing Sentimag was to come up with a detector that could reliably distinguish the minute magnetic signature produced by the magnetic particles in the body as they responded to the magnetic fields radiated by the device.

Endomag’s diagnostic system for breast cancer relies on an injectable fluid, branded as Sienna+, that contains superparamagnetic iron oxide nanoparticles. These particles accumulate in the lymph nodes that are the first to receive drainage from a breast tumour – the ‘sentinel’ lymph nodes. The Sentimag then locates these nodes for removal so that clinicians can check for signs of the cancer spreading.

An important advantage of Sienna+ is that, unlike the conventional radioactive tracers used for detecting lymph nodes, it does not require nuclear medicine to administer the injection, or careful timing to match the half-life of the radioisotope to the surgeon’s availability. Moreover, Sienna+ has a three-year shelf-life, rather than the six-hour half-life of a radioactive tracer, so hospitals and clinics far from nuclear medicine facilities can carry out sentinel lymph node biopsy. After about 20 minutes from injection, the particles migrate to the sentinel lymph nodes. The surgeon then uses Sentimag, probing as one would use a metal detector, to locate and remove the sentinel lymph nodes that contain Sienna+.

Equipment for use in operating theatres has to be easy to use and robust. Endomag has made steady progress in the design of its electronic systems, leading to ever smaller equipment. The electronics engineering combines a specialised low-noise amplifier with adaptive signal processing in a design that evolved to match the changing specifications of the probe.

Approval process

This technology has pushed back barriers in many fields. It has raised questions such as; is the company a medical diagnostics business? Does it manufacture surgical devices? Could it even find therapeutic applications for its technologies? The answer is that the company operates in all three areas. This can make it hard for investors, the media and, sometimes, competition judges, to know how to categorise it. The company’s technology crosses boundaries in biology, chemistry and physics and several disciplines of engineering, materials science and electronics.

Like all new medical technologies and treatments, the company has to navigate an approvals process that is complicated by the different regulatory approaches in different countries. Endomag had the advantage of being regulated as a device rather than as a pharmaceutical. This significantly reduces the cost of obtaining regulatory approval. In 2011, Endomag achieved its first important regulatory landmark when it received approval for using nanoparticles as a ‘medical device’. It was the first company to receive consent for nanoparticles and to commercialise them widely in Europe. The company hopes to follow its European success on this front by becoming the first nanoparticle device to receive regulatory approval by the US Food and Drug Administration.

There used to be a common understanding of what constituted a drug, with its chemical effects on the body, and what a device, with its physical intervention. That dividing line is starting to blur. At the nanometre scale, it is hard to differentiate between physical and chemical interactions. As a result, regulators have to write new legislation to approve the medical uses of nanomaterials.

The Sienna+/Sentimag system has also received an Investigational Device Exemption (IDE) from the US Food and Drug Administration. This is the first stage in the regulatory process in the US and allowed the company to start a pivotal clinical trial in support of full regulatory approval. The trial, underway at six sites across the US, is expected to conclude by the end of 2015. Endomag anticipates that it will receive regulatory approval in 2017, opening the way for a US commercial launch. 

Business development

When it came to raising funds, despite this complicated picture, the company did find investors who understood its plans and were willing to invest over £7 million, so far, into the business. Fortunately, unlike many healthcare start-ups, Endomag does not have to rely solely on investors to fund its development as it already generates income from sales of Sienna+ and Sentimag. Since its first sales in 2012, the company has seen triple-digit growth. Selling to hospitals and clinics, it has already treated 10,000 breast cancer patients across Europe, the Middle East and Australia. In 2014, the company’s revenues exceeded £2.5 million.

Endomag is now applying its underlying technologies for other medical applications. Next year, it plans to launch Sentimark, another innovation in the treatment of breast cancer. This new product came about partly because surgeons were asking the company for help to locate tumours as well as lymph nodes. Advances in screening for breast cancer now detect tumours earlier, when they are just a centimetre or two across, too small for surgeons to simply feel them. As surgeons want to remove as little tissue as possible, they need to pinpoint tumours as accurately as possible – see Sentimark.

Endomag has managed to develop its technologies and to negotiate the regulation processes with a relatively small staff. It achieves this by outsourcing some of its activities, including marketing and manufacturing the Sienna+/ Sentimag system. Now, the company is determined to grow through product development, manufacturing and sales rather than through licensing its intellectual property.

It is now developing its underlying technology platform in ways that will allow it to treat as well as locate cancers. Nanoparticles are similar in scale to the mechanisms of cancer, so Endomag is looking to build on established approaches, and existing pharmaceuticals, to detect and treat tumours. For example, magnetic nanoparticles can heat cancer cells in a way that does not kill them or the healthy surrounding tissue, but that makes the tumour more susceptible to chemotherapy. Interrupting the tumour’s ‘machinery’ makes the drug more effective and could mean delivering lower doses of traditionally toxic chemicals.

The treatment of other cancers also requires better ways of confirming the potential spread of tumours. Endomag has general approval for sentinel lymph node biopsy, which implies that doctors and surgeons can use the technology for any cancer. However, the company itself has taken a conservative strategy and has restricted its marketing to breast cancer, where it has evidence to show that its approach works.

This has not stopped surgeons from using the technology to investigate other cancers. While this means that they have to seek ethical approval before they do anything, surgeons have already started to use the Sienna+/Sentimag system in the treatment of prostate cancer. As clinical evidence becomes available from these activities by inquisitive surgeons, so long as it obtains approval, Endomag will be in a position to market its products for new conditions.

Thanks to this ‘viral uptake’ of Endomag’s medical devices, the company is developing advanced laparoscopic and endoscopic probes for other types of cancer including melanoma, prostate, thyroid, colon and cervical cancer.

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🧲 Find out more - Endomag's website. 

🩺 Update - Since this article was published, Endomag has been adopted by 1000+ hospitals, used in 45+ countries and treated 450,000+ patients. 

This article has been adapted from "Targeting cancers", which originally appeared in the print edition of Ingenia 65 (December 2015).