Nature defined cancer, with unsettling poetry, the “disease that spans the breadth of human experience” [1]. As much as we can elaborate, the gist of this thinking is that only a few human experiences are as all-encompassing as cancer. For patients and their loved ones, this is abundantly evident. Doctors, of course, are no onlookers: a patient’s body under general anaesthesia is a further chapter in a surgeon’s perpetual showdown. And in the operating room, technological innovations overcoming the existing constraints are, quite literally, vital.
One major issue in cancer surgery is that surgeons have no way of telling if a tissue is cancerous or not while they are operating. Although the thick mass of the main tumour can be identified visually and with the aid of scans, the edge and details elude the surgical eye. Doctors can be more or less conservative, yet they have no technology providing an accurate picture of the tumour mass. And what is worse is that, within cancer surgery, a more conservative choice might result in partial removal of the tumour, while a less conservative operation could irreversibly impair essential physiological functions. Furthermore, if surgeons suspect that a certain area is cancerous, they have to do a biopsy and take it to histological analysis. This process, however, takes time, which is a crucial resource during an operation. Anything that adds time to a procedure is not welcome. Also, a biopsy makes the recovery time longer and the procedure more traumatic.
In the early 2000s, as a junior faculty member at the Department of Radiology of the Massachusetts General Hospital, David Tuch had first-hand experience with these issues.
I would often get approached by other clinical departments asking for particular imaging solutions. I noticed that the surgeons would frequently come to us and say ‘Why don’t we have a way to detect cancer directly during surgery?’. At that time there was a huge clinical need for any company that could figure out how to do it. I looked into it and realised that the reason why there was no solution was that it’s incredibly hard: it has to be accurate, fast, cost-effective, and compatible with the clinical workflow. Dozens of companies and technologies over the years had been thrown at this problem, all failing spectacularly. Dr David Tuch, Founder & Executive Chairman – Lightpoint Medical
Not quite a rosy picture. It was only more than a decade later that David, mindful of this unsolved problem as well as of the more recent technical advancements, designed the first prototype of a specialised probe for accurate cancer imaging. In 2012, after years spent searching for this technology, Lightpoint was born.
You could easily get lost among the technical challenges that Lightpoint had to face during the early years. It would not be futile, at this point, to delve into the controversies of the old VC saw that “ideas are cheap, implementation is everything”. Be that as it may, David’s endeavour to pursue his vision against all odds is a superb blend of inventiveness and execution, besides being a staggering model of perseverance.
The result of this endeavour is the SENSEI® gamma probe, the first regulatory approved probe of its kind. The principle behind this solution is the same as in PET scans. A radiopharmaceutical, comprised of a radioactive compound linked to a targeting molecule, is injected into the patient’s bloodstream and binds to a target protein on the cancer cell. The emission of positrons from the compound generates gamma radiation, which is then detected by the PET scan. Selective accumulation of the radioactive compound in the cancerous tissue, therefore, allows for localisation of the tumour mass. SENSEI® is a gamma probe that detects the radiopharmaceutical in the same fashion, with the advantage of being as small as an AA battery. The miniaturised probe can easily be inserted into a surgical port and moved around the surgical cavity by using minimally invasive tools like graspers. The extreme manoeuvrability of this probe is ensured not only by its size but also by the flexible tether to which it is connected. This feature has undoubted advantages in operations for colorectal and prostate cancer since the pelvic anatomy is very restrictive. A conventional, rigid laparoscopic probe would never provide the manoeuvrability required in narrow anatomic regions.
Compatibility with minimally invasive surgery, unprecedented manoeuvrability, peerless detection accuracy: to put it simply, there is no competition in terms of standard of care. While the SENSEI® probe is designed to identify cancer spreading in lymph nodes, Lightpoint is now facing the next steps in its growth as a highly innovative company. The next development of a surface probe will feature even higher manoeuvrability and a wider range of applications. Neurovascular bundle preservation is a key challenge in this regard. During prostate cancer surgery, when the prostate is removed, these bundles are often cut as a precaution in case there is any additional cancer. Therefore, patients undergoing surgery suffer from incontinence, erectile dysfunctions and infertility, while doctors have no way of knowing whether the excised tissue is cancerous before the pathology report. Lightpoint’s next surface probe will detect cancer involvement in the nerve bundle so that surgeons can spare the bundles and preserve the patient’s physiological functions.
Further improvements also involve the pharmaceutical side of the technology. The strategic collaboration recently signed between Lightpoint and Telix is a major step towards even higher surgical precision, achieved by molecular-specific imaging agents. Imaging accuracy is an all-important parameter when it comes to coping with different types of cancer. The fact that not all tumours have the same metabolism determines the strategy employed to target the cancer cells. Fluorodeoxyglucose is the most common type of radiotracer, and its efficacy lies in the high uptake of glucose from cancerous tissues. However, prostate cancer is a notable example of why we are not dealing with a one-size-fits-all approach. Its reduced metabolic activity translates into a relatively low utilisation of glucose and, therefore, reduced effectiveness of FDG signalling.
There are several strategies aiming to address this issue by developing specialised compounds. In particular, prostate-specific membrane antigen ligands employing Technetium as radiolabel (for instance, 99mTc-PSMA) will significantly increase the accuracy in the detection and mapping of prostate cancer [2]. The collaboration between Lightpoint and Telix aims at leveraging the potential of these compounds to bring unprecedented precision into the operating room.
This agreement is part of a wider strategic shift for Lightpoint. In June this year, the company appointed Graeme Smith as new CEO, with David Tuch taking up the executive chair role. In David’s words, Graeme is a medical device industry veteran. His experience in the sector, from startups to larger companies, spans 32 years over which Graeme brought several companies to an exit. In all cases, the strategy was to lead the company to the best market position to succeed. This allowed him to appreciate what is attractive for larger companies about these technologies. Now, Lightpoint represents a formidable challenge and a just as extraordinary opportunity:
We are right at the hotspot. Robotic surgery is the in-thing at the moment, companies are investing millions to develop their robotic offerings. The number of robotic surgeries is increasing dramatically and will continue to do so. With SENSEI® we are in the perfect position to take advantage of this explosion. Graeme Smith, CEO – Lightpoint Medical
Lightpoint is building a strong network: distribution contracts are being discussed in 22 countries, with agreements already signed in Portugal, Spain, South Korea, Italy and Australia. This stage of the expansion will be crucial to building the clinical data so that distributors have the collateral to market the product.
While navigating these challenges, Graeme bears in mind this morsel of entrepreneurial wisdom and good governance: to ensure that the company is ready for an exit, it must be built as if there is no exit. Sure, we know that the ways of a company are unfathomable. But Lightpoint is here to stay and brighten the future of cancer surgery and patients’ hopes.
[1]The global challenge of cancer. Nature Cancer 1, 1-2 [2020].
[2] Tateishi, Ukihide: Prostate-specific membrane antigen (PSMA)–ligand positron emission tomography and radioligand therapy (RLT) of prostate cancer. Japanese Journal of Clinical Oncology 50(4): 349–356 [2020].