On 5 November, NRG PALLAS in Petten hosted the kick-off meeting for a groundbreaking initiative, "ILLUMINATE" (Increasing Lutetium Production While Leveraging Metabolic Imaging to Enhance Theranostics Effectiveness). This ambitious project unites an international consortium of leading academic and industrial experts, all committed to advancing the field of theranostics through innovations in lutetium production and metabolic imaging. Attendees at the meeting brought each other up to speed on their respective fields and set the stage for collaborative research, aiming to revolutionise treatment options by increasing the availability of lutetium and enhancing diagnostic precision and therapeutic efficacy in targeted therapies.

The collaborative research program aims to demonstrate the unique value of recently developed Metabolic Magnetic Resonance Imaging (MeMRI) visualising chemical processes in the body to significantly improve effective application of theranostics – an approach combining diagnosis, treatment, and continuous follow up of a condition. ILLUMINATE will provide the first clinical translation of MeMRI, with application to castrate resistant metastatic prostate cancer. Prostate cancer is the leading cause of death in a quarter of the world’s countries and is the most prevalent non-cutaneous cancer amongst men in Europe.

This project will pave the way for future expansion of the technology for use in earlier cancer stages and in other cancer types. In parallel, ILLUMINATE seeks to increase the overall availability of lutetium and develop more sustainable production methods.

ILLUMINATE is a four-and-a-half-year public-private partnership, funded by the Innovative Health Initiative (IHI), with representation from MedTech companies, research institutes, university hospitals and small- and medium-sized enterprises. The consortium is coordinated by UMC Utrecht, together with NRG PALLAS as a project lead. Other partners involved in the project are Euro-Bioimaging ERIC, Philips Medical Systems Nederland BV, Philips Gmbh Innovative Technologies, Synlab Sdn Spa, Consiglio Nazionale Delle Ricerche, University of Turin, Bracco Imaging Spa, Tesla Dynamic Coils BV, Wavetronica BV, Lund University, Amsterdam UMC, University Hospital Essen, and Lygature.

Using Lu-177-PSMA

Major advances in treating prostate cancer have been achieved using selective targeting of therapy with antibody-radioisotope combinations. Lutetium-177-Prostate-Specific Membrane Antigen (Lu-177-PSMA) is a highly promising targeted radioligand therapy recently approved for metastasised prostate cancer. It delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment, thus destroying the tumour cells. Lu-177-PSMA treatment is a so-called theranostics approach wherein imaging (PSMA PET/CT before, during and after treatment) and treatment itself are based on the same administered peptide, i.e. PSMA.

Supplementing standard clinical care with Lu-177 treatment has significantly prolonged the survival in prostate cancer patients. Despite the success of Lu-177-treatment, not all patients respond to it. Around 30% do not benefit from the treatment but do suffer from the side-effects such as nausea and fatigue (in already strongly debilitated individuals). Moreover, while theranostics provide for individualised treatment, challenges remain to successfully implement this approach in clinical practice. There is a lack of objective criteria for treatment selection and monitoring to optimise efficacy and safety. This hampers treatment accuracy.

MeMRI for assessing treatment response

Current approaches used to predict and monitor treatment efficacy in prostate cancer lack key features to assess treatment resistance or explain the underlying molecular mechanisms. MeMRI offers such capabilities. Recent studies have demonstrated that MeMRI can be used to rapidly and repeatedly assess heterogeneity in tumour persistence and treatment response. ILLUMINATE aims to demonstrate that this can improve treatment efficacy in prostate cancer through better dosing, preventing side effects, and quickly identifying patients who do not benefit from advanced treatment regimes.

“We have high expectations that MeMRI can aid in finding the best treatments for our patients as it can detect disturbed cell and energy metabolism directly after the first dose of treatment”, says project coordinator prof. Dennis Klomp, UMC Utrecht.

Increase future supply of Lu-177

The increased use of Lu-177-based therapies has resulted in an increased demand for this isotope and the raw material. Due to the large group of patients that can benefit from Lu-177 based treatments, it is foreseen that without appropriate development in Lu-177 production capacity, the demand for Lu-177 might exceed the supply. Moreover, the starting material is scarce and Europe is dependent on its supply from non-European countries. These hurdles pose serious challenges to the availability of radioisotope-based therapies within Europe in future.

“We are very proud that with our contribution to the ILLUMINATE project, we can increase the future supply of Lutetium-177 and decrease the dependency on supply of raw material. With the development of an up-scaled production process and recycling, we will ensure sustainable and reliable availability of Lutetium-177 chloride as starting material for Lu-177-based therapies in the future”, says project lead Karlijn van der Schilden, NRG PALLAS.