RSNA 2016: Baby Steps for Theranostics in Imaging

The life sciences field is inching closer each year into the era of Theranostics. The word sounds fancy, but, fortunately, its definition is simple. Theranostics stands for the integration of therapeutics and diagnostics. The promise of theranostics is huge: every step forward in this direction is also a step into the future of medicine – a medicine that is more predictive, translational, personalized, and precise than the one we practice today.

Theranostics is an up-and-coming field that only few innovative pharmaceutical companies can claim to be fully active in today. With new generations of in vitro diagnostics, molecular therapeutics or biosensors coming of age, we are getting closer to having ‘smart’ drugs that can detect diseased cells, attach to these cells, and then destroy them, providing end-to-end treatments for oncology or neurology. This begs the question, what’s in it for medical imaging?

Cross-Pollination and Synergies Between Pharma and Imaging
The fact that the life sciences field is top-of-mind in the area of theranostics doesn’t mean there is no place for imaging in this field; on the contrary. In fact, the cross-pollination between imaging advances and these ‘smart’ drugs are already a reality in the research realm, where they are seen as two synergistic levers for theranostics.

- Image the smart drugs in action: The ongoing advances in molecular imaging, which today allow visualizing form and function at once and more precisely than ever before, are of tremendous help in the discovery and clinical trial phases for new drug developments.

- Make these drugs even smarter: Similarly, the advances in contrast agents for X-ray or magnetic resonance imaging, radiotracers in nuclear medicine, or microbubbles in ultrasound, are helping make the drugs smarter in how they can recognize and bind to their target cells.

It should come as no surprise that we start to hear the word “Theranostics” at the medical imaging tradeshows, such as RSNA, particularly on the part of nuclear imaging industry participants. Siemens Healthineers, for example, showed several imaging advances that are very relevant in the context of theranostics, including continued advances in SPECT quantification, and an extended spectrum of radiopharmaceuticals supported by its quantification software, beyond the four most widely used ones.

Diagnostic and Therapeutic Ultrasound
Ultrasound, the modality that never ceases to push its limits and reinvent itself, is one amazing testbed for diagnostic and therapy integration. The new generation of wireless transducers can be almost embedded into a big-iron modality’s gantry for image guidance. Another convergence is in the brand new range of therapeutic focused ultrasound systems from various vendors and in various applications, such as MR-guided focused ultrasound. In the end, the difference between the diagnostic and therapeutic families of ultrasound products is a matter of beamforming and wave strength. As with X-ray, one can already see the signs of the two getting into grey territory.

High-Energy and Low-Energy X-Ray: Ambiguously Separated Industries[[{"type":"media","view_mode":"media_crop","fid":"55252","attributes":{"alt":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","class":"media-image media-image-right","id":"media_crop_1165283876582","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6906","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 250px; width: 200px; border-width: 0px; border-style: solid; margin: 1px; float: right;","title":"Nadim Michel Daher, Industry Principal, Medical Imaging and Imaging Informatics, Frost & Sullivan","typeof":"foaf:Image"}}]]
On the X-ray industry side, the radiation therapy field on one hand, and diagnostic/interventional imaging on the other hand, each have its own set of industry giants. The manufacturers of linear accelerators – Varian, Elekta, Accuray, etc. – and their counterparts in imaging – GE Healthcare, Siemens Healthineers, Philips Healthcare, etc.- today address largely separate market opportunities, respectively for treatment and diagnosis, respectively.

Both groups work with X-ray beams, but in very different ways. The first group is tasked with delivering a high-energy X-ray beam that is so thin and so focused that it can destroy diseased tissue without any harm to healthy surrounding tissue. The second group’s systems deliver a low-energy X-ray beam that is so diffuse and even that it can image disease without over-radiating patients. Therefore, the components and engineering processes are very different across these two industries, however, collaboration and integration between the two has been going on for many decades, and has taken a whole new turn over the last five years.

Integrated MR-Linac for Real-Time Image-Guided Therapy
The current state of the art in radiation therapy relies on images acquired prior to the actual treatment, which are used at the treatment planning phase. This means they cannot take into account organ movement during treatment. This is obviously less than ideal for precision. Imaging comes in again post-treatment, for response assessment. This means patients undergo multiple different procedures, each with its own experts, equipment, cost, and workflow. In the context of value-based care, there is a strong rationale for marrying the core competencies of radiotherapy and imaging vendors into one, integrated system.

This is exactly the concept that ViewRay has developed with its MRIdian system, an industry-first, integrated MR-linac (0.35 Tesla) system that has been FDA-approved since 2012. Installed in four U.S., one Netherlands, and one Korean location as of 2016, the system has been in clinical use since 2014 and treats more than 15 patients a day at Washington University in Saint Louis. Two similar developments, which are still investigational, are underway at the Cross Cancer Institute in Canada and the University of Sydney in Australia. It is in this competitive landscape that Philips and Elekta have step foot, with a high-field (1.5 Tesla) integrated MR-linac system. This represents a true industry breakthrough.

Image-Guided Therapy as Theranostics 1.0
In 2012, the two vendors established a consortium led by Elekta, with Philips as the partner for MRI, and prototyped the system together with their clinical partner at the University Medical Center Utrecht (UMCU) in the Netherlands, where a second unit was installed in 2014. The MD Anderson Cancer Center in Houston installed their own in 2015. In what appears to be an exponential turn, a number of additional clinical consortium partners have initiated or completed their installation in 2016 across the Netherlands, the UK, Canada, and the U.S. The stars seem aligned for the Philips-Elekta partnership to be the beginning of a huge success story: the new installations and order backlog are on a roll; the body of clinical publications are building up in the global academic community.

Philips Healthcare still has a considerable amount of cash on hand since the spin-off of the Lighting division, and despite the $1.2 billion acquisition of Volcano therapeutics in the very end of 2014 – the integration of which is proving very successful.  My own personal prediction as an analyst is, the day Philips has clarity on the FDA timeline for the new MR-linac, Philips will move ahead to acquire Elekta.