Targeted radionuclide therapy (TRT) is a nuclear medicine treatment. It involves administering radiopharmaceuticals to patients: radioligands.

These radioligands consist of:

• A radioactive isotope, either a beta or alpha emitter, capable of emitting radiation that destroys cancer cells.
• A vector or ligand, a molecule that recognises a target. This is often a receptor overexpressed by cancer cells or one with a specific affinity for the organ being targeted.

Once injected into the patient, the radioligand travels to, binds to and accumulates at its target. The isotope emits radiation that damages the DNA of cancer cells and destroys them. This targeted technique reduces damage to healthy tissue and is generally better tolerated by patients than chemotherapy.

At present, most radioligands with marketing authorisation use beta emitters, such as lutetium-177. However, beta particles travel several millimetres through tissue and deposit relatively little energy, which limits their effectiveness.

Beta-emitting radioligands therefore struggle to eradicate micrometastases and more aggressive tumours, often resulting in partial and short-lived treatment responses, with complete response rates below 15%.

An exceptionally powerful therapeutic approach: alpha therapy

In this context, alpha therapy represents a major therapeutic breakthrough.

Thanks to their very high linear energy transfer and a range of only a few dozen micrometres, alpha-emitting radioligands cause direct, lethal damage to tumour-cell DNA. They therefore offer unique potential for treating resistant tumours, tumours with highly aggressive biology and microscopic disease. Whereas some forms of radiation spread their energy over several millimetres, alpha particles act across a distance equivalent to only a few cells.

Despite the therapeutic promise of this innovative class of medicines, the development of alpha therapy is currently held back by a major structural barrier: the absence in Europe of integrated infrastructure covering the entire preclinical, clinical and translational continuum, while bringing together expertise in radiopharmacy, advanced dosimetry, radiobiology, radiation protection and access to patients.

A centre of excellence

The DART project at Gustave Roussy, led by Professors Désirée Deandreis and Éric Deutsch, is being conducted in collaboration with the Paris-Saclay Cancer Cluster (PSCC). Its aim is to provide industry partners with a preclinical, clinical, and translational centre of excellence designed to fast-track the development of alpha-emitting radioligands. It is built around three pillars:

• A certified preclinical infrastructure for proof-of-concept studies, specifically designed and equipped to conduct preclinical research with alpha-emitting radioisotopes in advanced mouse models, including syngeneic models and patient-derived xenografts (PDX). This infrastructure will combine regulatory compliance with access to Gustave Roussy’s unique expertise in immunology, DNA repair, omics and advanced dosimetry.
• An outstanding clinical facility dedicated to phase 0, I, II and III clinical trials, with substantial patient recruitment capacity at Europe’s leading cancer centre. The facility will include an extension of Gustave Roussy’s pharmacokinetics laboratory and radiopharmacy, together with a small-scale radiolabelling unit enabling radiopharmaceuticals to be labelled on site and clinical trials to begin more rapidly.
• An advanced translational research programme supported by an infrastructure integrating multimodal imaging, advanced dosimetry, artificial intelligence and molecular profiling. Its pioneering ambition is to develop integrated dosimetry at three levels, covering the tumour, healthy organs and the immune system, in order to elucidate the mechanisms of action, resistance and toxicity of alpha therapy alongside immune and molecular profiling of the patient and tumour tissue.

“DART is Europe’s first integrated ‘bench-to-bedside’ platform dedicated to alpha therapy. It has been designed to accelerate the development of this new treatment modality, from the preclinical stage through to clinical trials. It will also develop advanced dosimetry tools using artificial intelligence to personalise and optimise treatment,” explain Professor Désirée Deandreis, nuclear medicine physician and Deputy Head of Gustave Roussy’s Department of Imaging, and Professor Éric Deutsch, radiation oncologist and Medical Director of Gustave Roussy. “With DART, France and Europe will finally have a platform capable of turning alpha therapy into an accessible clinical reality by shortening the time between discovery and therapeutic application. Backed by an industrial ecosystem that is already mobilised, this public-private model positions Gustave Roussy and the PSCC as two key players in the future of oncology, where innovation translates directly into benefits for patients,” they conclude.