16 New horizons November 2014 Are holmium microspheres a next generation embolic for radioembolization? The CIRSE 2014 Excellence and Innovation Award was presented to the University Medical Centre of Utrecht team in The Netherlands where radioactive holmium-166 microspheres were developed. A spin-off company, Quirem Medical, seeks to commercially introduce these as QuiremSpheres in early 2015 for the treatment of liver cancer patients worldwide. Interventional News finds out more… T he team in Utrecht is led by Maurice van den Bosch (professor and head of Radiology), Marnix Lam (head of Nuclear Medicine), and associate professor Frank Nijsen, who is the inventor and project leader of the valorisation of the microspheres. What has your early research on radioactive holmium-166 poly L-lactic acid microspheres (Ho-166) shown? These microspheres were developed as an alternative to yttrium-90 (Y-90)-microspheres. Besides the high-energy betaradiation required for tumour destruction, these microspheres also emit low-energy gamma radiation, which can be used for quantitative SPECT imaging. Furthermore, the paramagnetic property of holmium allows for high-resolution MRI to be performed. The particles have been intensively tested for their stability, performance and imaging possibilities. Their biocompatibility and safety have been explored in laboratory animals and in a phase I clinical study in 15 patients, the results of which were published in Lancet Oncology. We have learned that Ho-166 radioembolisation is feasible and safe for the treatment of patients with unresectable and chemorefractory liver metastases and enables image-guided treatment. This year, the phase II efficacy study in patients with liver malignancies will be completed and two new studies are now open for recruitment. Presently, in vivo imaging and image-guided delivery of these holmium-loaded microspheres constitute the main points of our pre-clinical research. In the near future, these holmium microspheres will be able to be administered under real-time MRI. For the physician to see what he treats and to treat what he sees, it is imperative that he knows the precise doses and the exact distribution of the holmium particles, both in the liver and in the tumours, using either quantitative MRI or gamma scintigraphy. What potential advantages does radioembolization with Ho-166 offer over radioembolization with Y-90? Compared to the current radi- oembolization treatment using Y-90, the application of Ho-166 microspheres in the treatment of liver cancer brings several important benefits. Despite the efficacy of Y-90, the current radioembolization technique poses several shortcomings. One major disadvantage of radioembolization with Y-90 microspheres is that the microspheres are currently poorly visualised with medical imaging techniques. This hampers a good understanding of the relationship between dose and response of the tumour. Furthermore, the biodistribution during and after treatment cannot be observed in detail. Consequently, this can result in unsuccessful or suboptimal treatment. Similar to Y-90, holmium microspheres emit high-energy ßradiation that eradicates tumours. But, unlike Y-90, Ho-166 has the following benefits: It also emits γ-radiation. Gamma emission allows quantitative nuclear imaging and dosimetry, thereby preventing the over- and under-dosing. Moreover, it opens the possibility to monitor the patient during the treatment allowing the physician to adjust the Figure 1 L to R: Remmert de Roos, Marnix Lam, Jip Prince, Lenny Verkooijen, Frank Nijsen, Andor van den Hoven and Maurice van den Bosch treatment on-site to ensure that all tumours receive an optimal dose; Holmium is a paramagnetic element too, which allows visualisation with high resolution MRI. The application of this holmiumbased approach will thus revolutionise the treatment of cancer in all stages of the treatment: pretreatment planning and dosimetry; real-time monitoring during the actual treatment and monitoring efficacy after the treatment. Monitoring of the distribution enables interventionists to verify if lethal doses reach all cancer lesions in the liver. It enables the physician to adapt and optimise the treatment plan during the procedure and tailor it to the personal needs of the patient. To illustrate, figure 1 shows a patient’s liver with two metastatic tumours (tumour 1 and tumour 2). Tumour 1 is hit with the treatment dose (as shown by the holmium lighting up white for nuclear imaging and red for MRI) and will succumb to the radiation. However, the particles did not reach tumour 2. If left unseen (and untreated) this tumour will therefore keep growing and lead to patient mortality. Thus, the ability to visualise Ho-166 can improve treatment efficacy. s First, an assessment of the required dose must be made in the pre-treatment stage. As Y-90 cannot be detected using Single Photon Emission Computed Tomography (SPECT), a scout-dose of technetium is used instead. Unfortunately, the predictive value of technetium for Y-90 is known to be poor. In contrast Ho-166 can be detected using SPECT providing a major asset in dosimetry. Secondly, Ho-166 microspheres can be imaged by MRI after the treatment, resulting in high resolution maps of the microsphere distribution in the liver which gives powerful insight in the dose distribution to the tumours. This information is needed to decide on further treatment and thereby improve patient outcome. Finally, the half-life of holmium is shorter than that of yttrium (26.8 hours versus 64 hours). The short half-life of the holmium isotope means that the logistics need to be professionally organised to meet customer demand. However, the timely delivery of medical isotopes with a short half-life is already daily business for a large number of specialised transport companies. First dedicated UK support website for patients treated by radioembolization If interventional radiolosists need to direct patients to an online resource on radioembolization, here is a website that might prove useful… M y SIRT Story (http://www.mysirtstory.org.uk) is the first dedicated UK patient website to provide information and support to patients, and their families, about radioembolization or selective internal radiation therapy (SIRT). My SIRT Story has been developed in response to the recent decision by the NHS to make the treatment available to eligible patients in England and Scotland with liver cancer that has spread from the bowel or arisen in the bile ducts. My SIRT Story is a resource from the SIRT UK Network of clinicians and scientists that aims to share best practice, clinical experiences and patient information. It has been supported by Sirtex Medical and has been reviewed by the patient charity Beating Bowel Cancer to ensure that it provides patient-friendly information. Ricky Sharma, honorary consultant in Clinical Oncology at the Oxford University Hospitals NHS Trust and chair of the SIRT UK Network said, “It can be hard to take in all the information and to ask questions in a hospital consultation, especially when it is for a highly specialist cancer treatment like SIRT. This website is a great place for patients to find information and support in their own time. I am sure they will feel reassured by the stories and practical information offered.” Patient-friendly content about radioembolization My SIRT Story is an up-to-date patient resource that tells the stories of real people with liver cancer and their experiences with SIRT. The content has been developed to be as engaging as possible and contains short videos to help explain SIRT in an easily understandable way. It includes patient leaflets; patient stories; patient videos and a before, during and after procedure video that shows an actual SIRT procedure in progress.
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