Theranostics refers to the practice of pairing a diagnostic test and therapy that both bind to the same target. For example, a molecule targeting a protein cancer cell could carry with it a radioactive isotope that shows up on a scan to diagnose the disease, and then another radioactive isotope designed to destroy the cancer cell. Theranostics has the potential to be used as a safe, personalised treatment for a range of diseases, including cancer, but there are barriers to its wider application.
Focus on tough-to-treat prostate cancer cases
ILLUMINATE is a new IHI project that focuses on Lutetium-177-PSMA (Lu-177-PSMA), which is used to treat prostate cancer that has spread to other organs and become resistant to treatments such as hormone therapy. Prostate cancer cells, including those found outside the prostate, have high levels of a protein called prostate-specific membrane antigen (PSMA) on their surface. Lu-177-PSMA includes a tracer that sticks to PSMA, so that the radioactive Lutetium-177 is effectively delivered directly to the cancer cells.
Lu-177-PSMA helps a majority of patients who take it to live longer with their disease, although around 30% do not benefit from treatment. Furthermore, its success means that there might not be enough supply of Lutetium-177 to meet the demand.
A novel imaging technique to detect treatment response - fast
On the question of treatment response, ILLUMINATE will turn to an imaging technique called metabolic magnetic resonance imaging (MeMRI). As the name suggest, this is a type of MRI scan that is able to detect cell growth and energy processes in cells. It can therefore be used to identify, early on, patients whose cancer is more resistant to Lu-177-PSMA so that they can switch to alternative treatments.
ILLUMINATE hopes to further optimise MeMRI technology and associated decision-making tools so that it can be reliably used to predict treatment outcomes early on in the course of the treatment cycle. This will save patients from undergoing a treatment that ultimately will not help them. While ILLUMINATE focuses on advanced prostate cancer, in the longer term the project hopes its work on MeMRI will also pave the way for its use in earlier cancer stages and other cancer types.
“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,” said project coordinator Dennis Klomp of UMC Utrecht. “We are therefore grateful for the support of IHI and all project partners in rolling out the technology into a clinical trial”.
Keeping up with demand
Another focus of ILLUMINATE’s work is on ensuring there is enough Lu-177-PSMA to meet demand. The raw material used for its production, Ytterbium-176, is scarce and, in addition, only a handful of suppliers worldwide have the facilities to manufacture Lu-177, and their yields are typically low. ILLUMINATE aims to improve the different steps in the Lutetium-177 production process, and develop a new process for the recycling of Ytterbium-176.
“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,” said project lead Karlijn van der Schilden of NRG PALLAS. “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.”
Finally, the project team will work closely with patients, healthcare professionals and regulators to ensure the uptake of its results in the longer term.
The IHI theranostics portfolio
ILLUMINATE is one of three theranostics projects launched under IHI call 5, the other two being ACCELERATE.EU and Thera4Care.