PhD Defense | Diana Melis | Radiolabelling strategies towards the development of Re-188 radiopharmaceuticals for targeted radionuclide therapy

Radiolabelling strategies towards the development of Re-188 radiopharmaceuticals for targeted radionuclide therapy

Cancer is a major global health issue and the second leading cause of death worldwide. Traditional treatments such as surgery, chemotherapy, and external beam radiation therapy, although effective, are non-selective and often cause significant side effects. As a result, cancer treatment is increasingly shifting towards more personalized, targeted therapies. One promising approach is targeted radionuclide therapy (TRNT), which delivers radiation directly to tumours using specific targeting agents, thereby minimizing damage to healthy tissues. Among the radionuclides evaluated for TRNT, rhenium-188 (¹⁸⁸Re) stands out due to its favourable nuclear and chemical properties. These include its high-energy β-particle emission (E_max = 2.12 MeV), its emission of a 155 keV γ photon for imaging, its short half-life of 16.9 hours, and its cost-effective production via a ¹⁸⁸W/¹⁸⁸Re generator. Despite these advantages, ¹⁸⁸Re presents significant challenges in radiolabelling, largely due to the difficulty to reduce it from its +7 oxidation state, and its complex instability over time. These challenges have limited the development of ¹⁸⁸Re-radiopharmaceuticals, underlining the need for radiolabelling optimization to fully unlock its potential in TRNT. This PhD thesis aims to explore various radiolabelling strategies to advance the development of ¹⁸⁸Re-radiopharmaceuticals. It focuses on a wide range of topics, from constructing an in-house ¹⁸⁸W/¹⁸⁸Re generator and synthesising suitable bifunctional chelators, to the use of bioorthogonal click chemistry for radiolabelling heat-sensitive biomolecules, and preclinical evaluation. Additionally, various different oxidation states of ¹⁸⁸Re are explored. Ultimately, the aim is to highlight the therapeutic potential of ¹⁸⁸Re and promote its broader use in clinical applications.

Promoter:

• Gasser Gilles (University of Chimie Paris Tech)

SCK CEN mentors:

• Maarten Ooms
• Tomas Opsomer