In the case of solid tumors such as prostate and breast cancer, it is the ability of cancer cells to invade the surrounding tissues and to form distant metastases that leads to progression and poor prognosis. Numerous studies have implicated the serine-protease urokinase-type plasminogen activator (uPA) and its receptor (uPAR) to be of special importance in cancer invasion and metastasis. In line with this, have high expression levels of uPAR in tumor tissues been shown to be strongly associated with metastatic disease and thorough studies by immunohistochemistry and in situ hybridization have revealed low expression levels of uPAR in normal homeostatic tissues compared with malignant cancer lesions. All these characteristics together makes uPAR a potential ideal target for cancer imaging for improved diagnose, risk-stratification and treatment monitoring.Skriv dit afsnit her.
PET imaging is the fastest growing medical technology in modern medicine. The introduction of PET imaging have truly revolutionized especially cancer medicine with the use of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) for cancer improved diagnostic, staining and treatment monitoring. Today more than 2 million FDG-PET scans are performed each year. However, in a number of large-volume cancer types such as prostate, breast and colorectal cancer, a clear clinical need still exist for innovative non-invasive imaging technologies for optimal diagnose, since FDG-PET do not work in these cancer types.
Curasight builds its novel uPAR PET imaging approach on a deep understanding of the uPAR system and it’s role in cancer, together with extensive experience with translational molecular imaging, which has been obtained through more than a decade of research at Rigshospitalet and Prof. Andreas Kjaer’s laboratory at the University of Copenhagen. Curasight now introduces new peptide-based PET imaging ligands targeting uPAR. By non-invasive imaging of uPAR expression, high-volume cancers such as prostate- breast and colorectal cancer where FDG-PET do not work, improved diagnose, risk-stratification and treatment monitoring will be possible.
See interview with our CSO, Prof. Andreas Kjaer talking about Curasight's technology at BioPharm-America, Sep. 2016.
Skovgaard D, Persson M, Brandt-Larsen M, Christensen C, Madsen J, Klausen TL, Holm S, Andreasen FL, Loft A, Berthelsen AK, Pappot H, Brasso K, Kroman N, Hoejgaard L, Kjaer A. Safety, dosimetry and tumor detection ability of 68Ga-NOTA-AE105 - a novel radioligand for uPAR PET imaging: first-in-humans study. J Nucl Med. 2016, Sep. 8. ahead of print.
Persson M, Nedergaard MK, Brandt-Larsen M, Skovgaard D, Jørgensen T, Michaelsen SR, Madsen J, Lassen U, Poulsen HS, Kjaer A. uPAR is a promising new imaging biomarker in glioblastoma. J Nucl Med. 2016; 57(2): 272-278.
Persson M, Skovgaard D, Brandt-Larsen M, Christensen C, Madsen J, Nielsen CH, Thurison T, Klausen TL, Holm S, Jacobsen AL, Berthelsen AK, Ploug M, Pappot H, Brasso K, Kroman N, Højgaard L, Kjaer A. First-in-human uPAR PET: imaging of cancer aggressiveness. Theranostics. 2015;5(12): 1303-1316
Persson M, El Ali H, Binderup T, Pfeifer A, Madsen J, Rasmussen P, Kjaer A. Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR Imaging. Nucl Med Biol2014;41(3):290-5.
Persson M, Hosseini M, Madsen J, Jørgensen T, Jensen K, Kjaer A, Ploug M. Improved PET imaging of uPAR expression using new 64Cu-labeled cross-bridged peptide ligands: Comparative in vitro and in vivo studies. Theranostics. 2013;3(9):618-632.
Persson M, Kjaer A. Urokinase-type plasminogen activator receptor (uPAR) as a promising new imaging target: potential clinical applications. Clin Physiol Funct Imaging. 2013;33(5);329-37.
Persson M, Liu H, Madsen J, Cheng Z, Kjaer A. First 18F-labeled ligand for PET imaging of uPAR: In vivo studies in human prostate cancer xenografts. Nucl Med Biol. 2013;40(5):618-24.
Persson M, Madsen J, Østergaard S, Ploug M, Kjaer A. New 68Ga-labelled uPAR peptide antagonists for PET imaging of invasive phenotype: in vivo comparison of DOTA and NODAGA conjugated AE105. Nucl Med Biol. 2012;39(4):560-9.
Persson M, Madsen J, Østergaard S, Jensen MM, Jørgensen JT, Juhl K, Lehmann C, Ploug M, Kjaer A. Quantitative PET Imaging of Human uPAR with 64Cu-DOTA-AE105: Implications for localizing Cancer Invasion. J Nucl Med. 2012;53(1):138-45.
Kriegbaum M, Persson M, Haldager L, Alpizar-Alpizar W, Jacobsen B, Gårdsvoll H, Kjær A, and Ploug M. Rational targeting of the urokinase receptor (uPAR): Development of antagonists and non-invasive imaging probes. Current Drug Targets. 2011;12(12):1711-28.