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Tiny molecules, major success

Imaging & Image Guided Medicine

Looking back, Bert Wolterbeek is proud of what the Medical Delta ‘3Binding’ project has achieved. “Even though the project has ended, its relevance is multiplying,” he says. In 3Binding, clinicians, physicists, chemists and industrial partners joined forces to bring medical innovations to life – from understanding patient needs to developing nanoscale solutions – and with a keen eye to taking the end-results into production. At the heart of the programme: tiny molecules with room to spare.

Lighting up a tumour

The 3Binding concept was to load hollow organic molecules with a radioactive element for injection into the bloodstream of a patient. The molecules are functionalised with protein fragments that selectively bind to, for example, a tumour. In this way, the tumour is “lit up” by radioactive molecules. The radiation is used to provide a signal to an outside detector, revealing the location of the tumour with better accuracy than with common imaging modalities. “The bonus is that the radiation also kills the cancer cells, providing a radiotherapy treatment that starts immediately after injection of the molecules.” Visions of simple, fast, all-in-one cancer diagnosis and treatment lie ahead.

Clinical applications

Except for the application area of oncology (tracing and irradiating tumours), the 3Binding team also looked at cardiology (seeking out non-functional areas in the heart) and arthrosclerosis (providing an early warning of artery wall thickening). “In some of these areas, we managed to reach the pre-clinical stage,” says Wolterbeek, “in others not quite yet.” In particular, designing a molecule to target arthrosclerosis proved to be like looking for a needle in a haystack. “But we’re getting closer,” says Wolterbeek. “We’ve now identified families of molecules that might do the trick, but clinical innovations take a long time to reach the stage where they can be safely applied to patients. We can’t leap; we need to take it step by step.”

The innovative system will be used for pre-clinical research, for example to shed light on the effect of novel therapeutics in the treatment of Parkinson’s disease.

Combination of modalities

“Nonetheless, we have achieved wonderful results,” says Wolterbeek. One of these results is the combination of two complementary radiation imaging modalities: PET and SPECT. Both imaging modalities register the signal of radioactive “tracers” as they move through the body. However, each modality requires a different tracer, and each tracer visualizes a different process in the body. So why combine these modalities? Freek Beekman, responsible for this part of 3Binding, explains: “Consider dopamine; a chemical messenger that helps in the transmission of signals in the brain. While SPECT tracers reveal dopamine transport in the brain, PET tracers visualize the effect of a specific medicine. The combination of the two imaging systems allows us to study all relevant processes in the brain at once.” After being developed as part of the 3Binding project, the resulting machine was brought to the market by industrial partner MILabs. Over the past few years, the system has been installed worldwide at leading institutes such as Johns Hopkins University in the USA and the National Institute of Radiological Sciences in Japan. Here, the innovative system will be used for pre-clinical research, for example to shed light on the effect of novel therapeutics in the treatment of Parkinson’s disease.

Follow-up

Other breakthroughs that emerged from 3Binding include promising hollow molecule/radioisotope combinations, chemical approaches towards crafting the goal-seeking parts of the molecular complex, and procedures to test their ability to bind exclusively to a part of the body. “These are all further ingredients towards our final goal,” says Wolterbeek. “Follow-up projects are already underway.” For example, as part of the 3Binding project, radionuclide therapy using nano-carriers was explored. Here, Wolterbeek’s hollow molecules bring their radioactive payload to a tumour, where they emit alpha particles that kill cancer cells. The results obtained from this part of the 3Binding project helped start two new projects, one involving TU Delft and Erasmus MC, and the other TU Delft and the VU Medical Centre in Amsterdam, both projects bringing the 3Binding results a step nearer to the clinic.

3Binding has not just generated results; it has proven to be a flywheel for many more results still to come

Flywheel

Looking beyond the direct research results, Wolterbeek emphasises the key impact of 3Binding: it highlighted the potential of a multidisciplinary collaboration covering the full innovation chain. The 3Binding partnership has spawned new collaborative projects, featuring subsets of 3Binding collaborators, including an international programme mimicking the 3Binding philosophy. “For example, these follow-up projects, replace the organic molecules by inorganic counterparts offering different functionalities, or focus on a different type of radioisotope.” The collaborative spirit of 3Binding has really taken hold of Wolterbeek. Even his most recent endeavour, the Dutch Isotope Valley (DIVA), features partners that cover the innovation chain, from R&D to large-scale production. Clearly, 3Binding has not just generated results: it has proven to be a flywheel for many more results still to come.

Interview by: DBAR tekst & redactie