TY - JOUR
T1 - Safety, Dosimetry, and Tumor Detection Ability of 68Ga-NOTA-AE105
T2 - First-in-Human Study of a Novel Radioligand for uPAR PET Imaging
AU - Skovgaard Lund, Dorthe
AU - Persson, Morten
AU - Brandt-Larsen, Malene
AU - Christensen, Camilla
AU - Madsen, Jacob
AU - Klausen, Thomas Levin
AU - Holm, Søren
AU - Andersen, Flemming Littrup
AU - Loft, Annika
AU - Berthelsen, Anne Kiil
AU - Pappot, Helle
AU - Brasso, Klaus
AU - Kroman, Niels
AU - Højgaard, Liselotte
AU - Kjaer, Andreas
N1 - © 2017 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - The overexpression of urokinase-type plasminogen activator receptors (uPARs) represents an established biomarker for aggressiveness in most common malignant diseases, including breast cancer (BC), prostate cancer (PC), and urinary bladder cancer (UBC), and is therefore an important target for new cancer therapeutic and diagnostic strategies. In this study, uPAR PET imaging using a 68Ga-labeled version of the uPAR-targeting peptide (AE105) was investigated in a group of patients with BC, PC, and UBC. The aim of this first-in-human, phase I clinical trial was to investigate the safety and biodistribution in normal tissues and uptake in tumor lesions. Methods: Ten patients (6 PC, 2 BC, and 2 UBC) received a single intravenous dose of 68Ga-NOTAAE105 (154 6 59 MBq; range, 48-208 MBq). The biodistribution and radiation dosimetry were assessed by serial whole-body PET/CT scans (10 min, 1 h, and 2 h after injection). Safety assessment included measurements of vital signs with regular intervals during the imaging sessions and laboratory blood screening tests performed before and after injection. In a subgroup of patients, the in vivo stability of 68Ga-NOTA-AE105 was determined in collected blood and urine. PET images were visually analyzed for visible tumor uptake of 68Ga-NOTA-AE105, and SUVs were obtained from tumor lesions by manually drawing volumes of interest in the malignant tissue. Results: No adverse events or clinically detectable pharmacologic effects were found. The radioligand exhibited good in vivo stability and fast clearance from tissue compartments primarily by renal excretion. The effective dose was 0.015 mSv/MBq, leading to a radiation burden of 3 mSv when the clinical target dose of 200 MBq was used. In addition, radioligand accumulation was seen in primary tumor lesions as well as in metastases. Conclusion: This first-in-human, phase I clinical trial demonstrates the safe use and clinical potential of 68Ga- NOTA-AE105 as a new radioligand for uPAR PET imaging in cancer patients.
AB - The overexpression of urokinase-type plasminogen activator receptors (uPARs) represents an established biomarker for aggressiveness in most common malignant diseases, including breast cancer (BC), prostate cancer (PC), and urinary bladder cancer (UBC), and is therefore an important target for new cancer therapeutic and diagnostic strategies. In this study, uPAR PET imaging using a 68Ga-labeled version of the uPAR-targeting peptide (AE105) was investigated in a group of patients with BC, PC, and UBC. The aim of this first-in-human, phase I clinical trial was to investigate the safety and biodistribution in normal tissues and uptake in tumor lesions. Methods: Ten patients (6 PC, 2 BC, and 2 UBC) received a single intravenous dose of 68Ga-NOTAAE105 (154 6 59 MBq; range, 48-208 MBq). The biodistribution and radiation dosimetry were assessed by serial whole-body PET/CT scans (10 min, 1 h, and 2 h after injection). Safety assessment included measurements of vital signs with regular intervals during the imaging sessions and laboratory blood screening tests performed before and after injection. In a subgroup of patients, the in vivo stability of 68Ga-NOTA-AE105 was determined in collected blood and urine. PET images were visually analyzed for visible tumor uptake of 68Ga-NOTA-AE105, and SUVs were obtained from tumor lesions by manually drawing volumes of interest in the malignant tissue. Results: No adverse events or clinically detectable pharmacologic effects were found. The radioligand exhibited good in vivo stability and fast clearance from tissue compartments primarily by renal excretion. The effective dose was 0.015 mSv/MBq, leading to a radiation burden of 3 mSv when the clinical target dose of 200 MBq was used. In addition, radioligand accumulation was seen in primary tumor lesions as well as in metastases. Conclusion: This first-in-human, phase I clinical trial demonstrates the safe use and clinical potential of 68Ga- NOTA-AE105 as a new radioligand for uPAR PET imaging in cancer patients.
KW - Adult
KW - Aged
KW - Biomarkers, Tumor/metabolism
KW - Female
KW - Heterocyclic Compounds/pharmacokinetics
KW - Humans
KW - Male
KW - Metabolic Clearance Rate
KW - Middle Aged
KW - Molecular Imaging/methods
KW - Neoplasms/diagnostic imaging
KW - Oligopeptides/pharmacokinetics
KW - Organ Specificity
KW - Pilot Projects
KW - Positron-Emission Tomography/methods
KW - Radiation Dosage
KW - Radiation Exposure/analysis
KW - Radiopharmaceuticals/pharmacokinetics
KW - Receptors, Urokinase Plasminogen Activator/metabolism
KW - Reproducibility of Results
KW - Sensitivity and Specificity
KW - Tissue Distribution
KW - Whole-Body Counting
U2 - 10.2967/jnumed.116.178970
DO - 10.2967/jnumed.116.178970
M3 - Journal article
C2 - 27609788
SN - 0161-5505
VL - 58
SP - 379
EP - 386
JO - The Journal of Nuclear Medicine
JF - The Journal of Nuclear Medicine
IS - 3
ER -
