First-in-Human Study of [ 68 Ga]Ga-NODAGA-E[c(RGDyK)] 2 PET for Integrin α v β 3 Imaging in Patients with Breast Cancer and Neuroendocrine Neoplasms: Safety, Dosimetry and Tumor Imaging Ability.

Autor: Clausen MM; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; Department of Oncology, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Carlsen EA; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Christensen C; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Madsen J; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Brandt-Larsen M; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Klausen TL; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Holm S; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Loft A; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Berthelsen AK; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Kroman N; Department of Breast Surgery, Copenhagen University Hospital-Herlev/Gentofte Hospital, 2730 Herlev, Denmark., Knigge U; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark.; Departments of Clinical Endocrinology and Surgical Gastroenterology, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark., Kjaer A; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.; ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Diagnostics (Basel, Switzerland) [Diagnostics (Basel)] 2022 Mar 30; Vol. 12 (4). Date of Electronic Publication: 2022 Mar 30.
DOI: 10.3390/diagnostics12040851
Abstrakt: Arginine-Glycine-Aspartate (RGD)-recognizing cell surface integrins are involved in tumor growth, invasiveness/metastases, and angiogenesis, and are therefore an attractive treatment target in cancers. The subtype integrin α v β 3 is upregulated on endothelial cells during angiogenesis and on tumor cells. In vivo assessment of integrin α v β 3 is possible with positron emission tomography (PET). Preclinical data on radiochemical properties, tumor uptake and radiation exposure identified [ 68 Ga]Ga-NODAGA-E[c(RGDyK)] 2 as a promising candidate for clinical translation. In this first-in-human phase I study, we evaluate [ 68 Ga]Ga-NODAGA-E[c(RGDyK)] 2 PET in patients with neuroendocrine neoplasms (NEN) and breast cancer (BC). The aim was to investigate safety, biodistribution and dosimetry as well as tracer uptake in tumor lesions. A total of 10 patients (5 breast cancer, 5 neuroendocrine neoplasm) received a single intravenous dose of approximately 200 MBq [ 68 Ga]Ga-NODAGA-E[c(RGDyK)] 2 . Biodistribution profile and dosimetry were assessed by whole-body PET/CT performed at 10 min, 1 h and 2 h after injection. Safety assessment with vital parameters, electrocardiograms and blood tests were performed before and after injection. In vivo stability of [ 68 Ga]Ga-NODAGA-E[c(RGDyK)] 2 was determined by analysis of blood and urine. PET images were analyzed for tracer uptake in tumors and background organs. No adverse events or pharmacologic effects were observed in the 10 patients. [ 68 Ga]Ga-NODAGA-E[c(RGDyK)] 2 exhibited good in vivo stability and fast clearance, primarily by renal excretion. The effective dose was 0.022 mSv/MBq, equaling a radiation exposure of 4.4 mSv at an injected activity of 200 MBq. The tracer demonstrated stable tumor retention and good image contrast. In conclusion, this first-in-human phase I trial demonstrated safe use of [ 68 Ga]Ga-NODAGA-E[c(RGDyK)] 2 for integrin α v β 3 imaging in cancer patients, low radiation exposure and favorable uptake in tumors. Further studies are warranted to establish whether [ 68 Ga]Ga-NODAGA-E[c(RGDyK)] 2 may become a tool for early identification of patients eligible for treatments targeting integrin α v β 3 and for risk stratification of patients.
Databáze: MEDLINE
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