Molecular imaging and targeted therapy of the aggressive phenotype: development of uPAR theranostics for cancer patients

Projektinformationen

uPET

ID Finanzhilfevereinbarung: 670261

DOI

10.3030/670261

Projekt abgeschlossen

EK-Unterschriftsdatum 7 September 2015

Startdatum 1 Oktober 2015

Enddatum 31 März 2021

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 2 072 000,00

EU-Beitrag

€ 2 072 000,00

Koordiniert durch

REGION HOVEDSTADEN
Denmark

Periodic Reporting for period 4 - uPET (Molecular imaging and targeted therapy of the aggressive phenotype: development of uPAR theranostics for cancer patients)

Berichtszeitraum: 2020-04-01 bis 2021-03-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

For practice of personalized medicine in cancer, non-invasive tools for diagnosing at the molecular level are needed. Molecular imaging methods are capable of this while at the same time circumventing sampling error as the whole tumor burden is evaluated.

Based on our recent breakthrough with the the first-ever clinical PET scan of uPAR, a proteolytic system known to be strongly associated with metastatic potential in most cancer forms, we sought to develop new tools for improving personalized medicine in cancer. We worked along lines that could improve surgery, improve therapy planning and finally uPAR-targeted radionuclide therapy. The ambition was to demonstrate that the new concept of uPAR-targeted technologies could fulfill significant unmet needs in prostate and other cancer types.

The aim of the project was to develop, evaluate and translate into patients, new and highly innovative molecular imaging methods with PET and optical imaging demonstrating the aggressiveness and metastatic potential of cancers. This was successfully achieved. Also work with radionuclide therapy in preclinical models was undertaken. Together, these methods will support practicing personalized medicine in cancer patients.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Most important achievements
• Development of uPAR-PET imaging for imaging of the aggressive cancer phenotype. We translated the technology into first-in-human use and have initiated several phase II clinical trials. Most notably, we have demonstrated in prostate cancer that we can use uPAR-PET/MR as a non-invasive biopsy, replacing random, invasive biopsies which are hampered by side effects as bleeding and infection. So far, more than 400 patients with various cancer types have been scanned with the technology.
• Development of uPAR-targeted optical imaging for delineation of tumors during surgery. Following an array of preclinical proof-of-concept studies demonstrating how uPAR optical imaging could assist in cancer surgery, we were ready to prepare for clinical use. The technology was out-licensed to a spin-out company, FluoGuide, that is currently undertaking a first-in-human phase I/IIa study. So far, 18 patients with brain cancer have successfully received the optical probe.
• Development of uPAR targeting radionuclide therapy for the invasive cancer phenotype. We have continued our work with uPAR-targeting radionuclide therapy using 177Lu as the radioisotope (beta-emitter with range of 1 mm). Here, we have focused on development of a next-generation ligand and successfully synthesized a new ligand that has demonstrated improved binding to uPAR compared to our starting molecule. We will continue this work in order to proceed into humans once a sufficiently high uptake and retention in the tumors have been observed.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Novel concepts of using uPAR targeting for PET imaging, radionuclide therapy and optical imaging. We expect the technologies to be translated into human testing during the project.

uPAR optical imaging