title: First-in-human uPAR PET: Imaging of Cancer Aggressiveness.
abstract: A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with (64)Cu for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of (64)Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment with laboratory blood screening tests was performed before and after PET ligand injection. In a subgroup of the patients, the in vivo stability of our targeted PET ligand was determined in collected blood and urine. No adverse or clinically detectable side effects in any of the 10 patients were found. The ligand exhibited good in vivo stability and fast clearance from plasma and tissue compartments by renal excretion. In addition, high uptake in both primary tumor lesions and lymph node metastases was seen and paralleled high uPAR expression in excised tumor tissue. Overall, this first-in-human study therefore provides promising evidence for safe use of (64)Cu-DOTA-AE105 for uPAR PET imaging in cancer patients.
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Persson
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark. ; 2. Department of Physiology and Nuclear Medicine, University hospital of Copenhagen, Gentofte, Denmark.
authors.forename: Dorthe
authors.initials: D
authors.lastname: Skovgaard
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Malene
authors.initials: M
authors.lastname: Brandt-Larsen
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Christensen
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Carsten H
authors.initials: CH
authors.lastname: Nielsen
authors.affiliation: 3. Finsen Laboratory, Rigshospitalet, Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tine
authors.initials: T
authors.lastname: Thurison
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Thomas Levin
authors.initials: TL
authors.lastname: Klausen
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Holm
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Annika
authors.initials: A
authors.lastname: Loft
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Anne Kiil
authors.initials: AK
authors.lastname: Berthelsen
authors.affiliation: 3. Finsen Laboratory, Rigshospitalet, Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Ploug
authors.affiliation: 4. Department of Oncology, Finsen Centre, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Pappot
authors.affiliation: 5. Copenhagen Prostate Cancer Center, Department of Urology, Abdominal Centre, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brasso
authors.affiliation: 6. Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Kroman
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Højgaard
authors.affiliation: 1. Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D009842:Oligopeptides / Q000008:administration & dosage / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D011485:Protein Binding; D055293:Receptors, Urokinase Plasminogen Activator / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology
chemical_list: D003301:Copper Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D055293:Receptors, Urokinase Plasminogen Activator; C000609091:beta-cyclohexylalanyl-phenylalanyl-seryl-arginyl-tyrosyl-leucyl-tryptophyl-serine; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
keywords: PET; clinical trial; uPAR