First-in-human uPAR PET: Imaging of Cancer Aggressiveness

Theranostics. 2015 Sep 13;5(12):1303-16. doi: 10.7150/thno.12956. eCollection 2015.


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.

Keywords: PET; clinical trial; uPAR.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / pathology
  • Copper Radioisotopes / administration & dosage
  • Copper Radioisotopes / metabolism
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • Heterocyclic Compounds, 1-Ring / administration & dosage
  • Heterocyclic Compounds, 1-Ring / metabolism
  • Humans
  • Male
  • Middle Aged
  • Molecular Imaging / methods*
  • Oligopeptides / administration & dosage
  • Oligopeptides / metabolism
  • Positron-Emission Tomography / methods*
  • Prognosis
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / pathology
  • Protein Binding
  • Receptors, Urokinase Plasminogen Activator / analysis*
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology


  • Copper Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Oligopeptides
  • Receptors, Urokinase Plasminogen Activator
  • beta-cyclohexylalanyl-phenylalanyl-seryl-arginyl-tyrosyl-leucyl-tryptophyl-serine
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid