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Cancer is the second leading cause of mortality in EU countries after cardiovascular diseases. Every year, 2.6 million people are diagnosed with the disease, which kills another 1.2 million people. Over 40 % of cancer cases are preventable, and mortality can also be reduced through earlier diagnosis and the provision of more timely and effective treatments.
Positron emission tomography (PET) scanners have been used to detect cancer and evaluate treatment effectiveness for decades, with next-generation systems such as total-body PET scanners promising to make this imaging technique even better in the coming years.
But not all improvements require new equipment. Thanks to funding under the uPET project, Andreas Kjaer’s team at the University of Copenhagen and Rigshospitalet have successfully developed the first-ever clinical scan of uPAR, a marker known to be strongly associated with metastatic potential in most cancer forms. Using this technique, standard PET scanners can now show how aggressive a cancer really is.
“This is an important step forward for therapy planning,” says Kjaer, professor and chief physician at the Rigshospitalet’s and University of Copenhagen’s Departments of Clinical Physiology and Nuclear Medicine and Biomedicine. “We have shown that uPAR-PET in many cases beats histological evaluation. It circumvents the risk of sampling error – where the tissue evaluated is not representative of the state of the disease – and doesn’t overlook any aspect of the cancer or metastases. We really get to see everything with whole-body PET imaging.”
A cross-cancer type solution
uPAR is not only a marker of aggressiveness. It is also involved in the process of invasion, which according to Kjaer probably contributes to its robustness in predicting overall survival and progression. Another advantage of uPAR-PET scanning is the fact that uPAR is expressed in around 80 % of solid tumours, which means it can be beneficial to many cancer patients independently of the cancer form they’re facing.
So far, the team has successfully applied this technique to breast, prostate, brain and head-and-neck cancer, as well as to neuroendocrine tumours. “We wanted to focus on prostate and breast cancer first because this was where the largest unmet medical needs could be found,” adds Kjaer. “In prostate cancer, we want to use uPAR-PET as a non-invasive biopsy for better risk stratification in localised disease. This is to avoid overtreatment in these patients in a context where an estimated 80 % of prostatectomies are being performed unnecessarily and 70 % of these patients face side-effects such as impotence and urinary incontinence. uPAR-PET will not only improve the lives of prostate cancer patients, but also be cost-effective,” Kjaer explains.
With uPAR-PET successfully tested on more than 400 patients, Kjaer and his team are now focusing on technology improvements. They are notably looking into uPAR-targeted radionuclide therapies, which will use uPAR binding to irradiate tumours locally with high precision. “We find uPAR to be a ‘smart target’ for this purpose. The more aggressive the cancer cells are, the more radionuclide will be bound to it. Concretely, this means that we get most radiation to the parts of the tumour that need it the most,” he remarks.
If the team’s research proves fruitful, uPAR-targeted radionuclide therapy could be a real game changer applicable to many types of cancer.