ILLUMINATE: Increasing lutetium production while leveraging metabolic imaging to enhance theranostics effectiveness

ILLUMINATE will provide the first clinical translation of metabolic-MRI, with application to castrate resistant metastatic prostate cancer. This 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). The consortium is coordinated by UMC Utrecht, together with NRG PALLAS as a project lead.  

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. 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 metastasized prostate cancer. Lu-177-PSMA treatment is a so-called theranostics approach wherein imaging and treatment itself are based on the same administered peptide, i.e. PSMA.  

Despite the success of Lu-177-treatment, not all patients respond to it but they do suffer from the side effects. To optimize efficacy and safety for patients, objective criteria are needed for treatment selection and monitoring. 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. Metabolic-MRI offers such capabilities. 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 metabolic-MRI 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. We are therefore grateful for the support of IHI and all project partners in rolling out the technology into a clinical study”, says project coordinator prof. Dennis Klomp, UMC Utrecht. 

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 radioisotopebased 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 self-sufficient production process, we will ensure sustainable and reliable availability of Lu-177-based therapies in the future. We are thankful to the IHI and to all project partners that assist in the development of new treatments and strive after improvement of efficacy with new technologies”, says project lead Karlijn van der Schilden, NRG PALLAS.  

Read the ILLUMINATE consortium press release here.