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In the University of Warwick and King’s College London, the FIELD-LAB of NRG has found its first international partners. Despite the significant barriers created by both the COVID-pandemic and Brexit, researchers and scientists on both sides of the Channel managed to get things started and hope to present exciting new findings in due time. Dr Cinzia Imberti, Sir Henry Wellcome Postdoctoral Fellow, University of Warwick, UK and Nora Klaassen, project manager R&D at Field-Lab, Petten, the Netherlands, shed some light on how this collaboration started and its hopes for the future.
Imberti first explains the joint involvement of both the University of Warwick and King’s College London. “Although employed by the University of Warwick, I perform the radionuclide work in the lab at King’s College due to the availability of the facilities.” Nevertheless, this is familiar ground for Imberti, as she completed her PhD in radionuclide imaging at King’s College London. This was followed by a fellowship at the University of Warwick, investigating the mechanism of action of platinum agents, focusing specifically on smarter platinum drugs. “These are completely inactive until they are exposed to light as a result of which they photodecompose, releasing toxic molecules which act as anti-cancer agents”, Imberti says. “These agents allow for very precise treatment in early-stage cancer, by using light to switch on their anti-cancer activity only at the tumour site, minimising side effects in healthy organs.”
With her robust background in radionuclide imaging, Imberti was brought into contact with FIELD-LAB to investigate the possibilities of collaboration on her platinum research. “This proved to be interesting for King’s College London too, as they are trying to find new ways to understand cancer biology with imaging and in particular resistance to cisplatin. In fact, this project has two arms: the first on new photoactivatable platinum agents and the second on the mechanism of action and resistance of established agents such as cisplatin.” Imberti then visited FIELD-LAB in January 2020, and her project was considered to be feasible. She recalls: “It became clear that, in order for our collaboration to be fruitful, we would have to become a partner of FIELD-LAB, which we did.”
Imberti and her team started working and were supplied with the material to do so by FIELD-LAB. Klaassen recalls the logistic challenges which accompanied this: “The first shipment was done in November 2020, and the second in January 2021, when the Brexit had just come into force. This led to some important logistic changes such as a separate clearance of the nuclear shipment and transporting through the Channel Tunnel in one go as is compulsory when transporting nuclear product.” As if this was not enough of a challenge, the British variation of the coronavirus also reared its head in January, leading to enormous build-ups of traffic jams on both sides of the Channel. Nevertheless, it all worked out as it should be with the nuclear material deliveries made in time. “All in all, our logistic department spent a lot of time in getting everything ready”, Klaassen remembers.
“These agents allow for very precise treatment in early-stage cancer."
The first part of her extensive research was assessing whether the photactivatable compound could be made radioactive. “This in itself was challenging due to the rather long synthesis of the compound and the short half-life of radioactive platinum, meaning that the radioactivity would be gone in a few days. There were concerns about self-activation too, as the compound is light-activatable and radiation is a form of light. However, the compound itself has shown to be stable. Recently, we managed to inject the compound in an animal for the first time and observe the distribution of the compound in the body. The compound was considered safe as it did not seem to negatively impact the animal. These findings provide the foundation to investigate the same compound when it is injected in tumour models to see in which timeframe the compound actually gets into the tumour. This is an important piece of information, as we have to know when exactly to shine a light on the tumour to activate the compound.” The other line of research Imberti is working on involves cisplatin. As it is a clinically approved drug, Imberti and her colleagues were able to work in animal models straightaway. “We know that some tumours are sensitive to cisplatin and respond whilst others are not. In a group of animals sensitive to cisplatin and a group of animals which are not sensitive, we are investigating whether there are any differences in the distribution of platinum in the body when both groups have been injected with radioactive cisplatin. Although very preliminary, it looks like there may indeed be some differences.” Other future lines of interest are the role of copper in conjunction with cisplatin. “Cisplatin is thought to use the same entry into the cancer cells as copper. Thus, we wondered: can radioactive copper accumulation in the tumour predict cisplatin accumulation (or lack of) and sensitivity? This touches upon a very fundamental research question on the mechanism of cisplatin accumulation in cancer, which has not yet been fully understood.”
They are trying to find new ways to understand cancer biology with imaging and in particular resistance to cisplatin."
The current collaboration between FIELD-LAB and King’s College London/University of Warwick is interesting for a number of reasons, Klaassen explains. “First of all, it is very encouraging for everyone involved if you are able to contribute to the wellbeing of cancer patients”, she says. “Also, having an international partner is generally considered to be a positive feature, and we strive to expand our number of international collaborators significantly. By doing so, we generate more brand awareness for FIELD-LAB and our activities. Furthermore, this collaboration enables us to create and expand intellectual property together, serving as a financial source and generating income. In this case, it may mean that research leads to a product or a method which can be marketed. FIELD-LAB will have added to that as well as it has been developed by using material supplied by us.”
Imberti finds it intriguing that although cisplatin has been available in the clinic since 1978 and its mechanism of action is fairly well understood, certain aspects are yet to be elucidated, such as how cisplatin enters the cells. “Therefore, it is an exciting field to work in, especially as until very recently, we did not have the possibilities to do proper whole body imaging. The amount of radioactivity per gram cisplatin was not sufficient to generate good quality images. It has been a game changer to be able to produce this type of cisplatin in a form that is useful for Single Photon Emission Computed Tomography imaging. We can now really track cisplatin in the body and see how it changes over time.”
Apart from taking part in this particular European collaboration, FIELD-LAB also aims to provide opportunities for its partners to share ideas and insights between them. A good example is the connection between King’s College London/University of Warwick and the Dutch VU Medical Center (VUmc) and the Antonie van Leeuwenhoek (AvL) hospital, both in Amsterdam. VUmc/AvL are working on CISSPECT, a promising imaging agent to predict the effectivity of cisplatin treatment and to prevent severe kidney toxicity. By using CISSPECT, the uptake of cisplatin in the tumour can be measured and patients for cisplatin chemotherapy can be selected, as well as assessing the concentration of cisplatin in the kidneys. As such, CISSPECT can improve cisplatin treatment and prevent patients suffering side effects such as kidney failure, loss of hearing, nausea and tiredness. Klaassen explains that during a recent partner meeting, the two consortia were eager to hear from each other experiences. “Every six months, we organise a dedicated meeting for our partners to share their scientific results and progress. During this Skype meeting, King’s College London/University of Warwick and VUmc/AvL met for the first time and shared information about their projects. By doing so, they can help each other.” Imberti adds that her two sponsors, Professor Peter Stadler and Professor Phil Blower, possess the expertise in platinum chemistry and in radionuclide imaging which will both be useful for other partners in FIELD-LAB, who are working in similar lines of research. “The beauty of FIELD-LAB lies in providing a form of open European collaboration, by offering all partners valuable information and knowledge”, Imberti concludes.
“The beauty of FIELD-LAB lies in providing a form of open European collaboration, by offering all partners valuable information and knowledge”