First-in-Humans PET Imaging of Tissue Factor in Patients with Primary and Metastatic Cancers Using 18 F-labeled Active-Site Inhibited Factor VII ( 18 F-ASIS): Potential as Companion Diagnostic.

Autor: Loft M; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of 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, Denmark., Clausen MM; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark.; Department of Oncology, Copenhagen University Hospital - Rigshospitalet, 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, Denmark., Hansen CP; Department of Surgery, Copenhagen University Hospital - Rigshospitalet, Denmark., Kroman N; Department of Breast Surgery, Copenhagen University Hospital - Rigshospitalet, Denmark., Langer SW; Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Denmark.; Department of Clinical Medicine, University of Copenhagen, Denmark., Høgdall C; Department of Gynecology, Copenhagen University Hospital - Rigshospitalet, Denmark and., Madsen J; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark., Gillings N; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark., Nielsen CH; Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Denmark.; Minerva Imaging ApS, 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, 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, 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, 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, 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, Denmark; akjaer@sund.ku.dk.
Jazyk: angličtina
Zdroj: Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2022 Dec; Vol. 63 (12), pp. 1871-1879. Date of Electronic Publication: 2022 May 19.
DOI: 10.2967/jnumed.122.264068
Abstrakt: Tissue factor (TF) expression in cancers correlates with poor prognosis. Recently, the first TF-targeted therapy was approved by the U.S. Food and Drug Administration for cervical cancer. To unfold the potential of TF-targeted therapies, correct stratification and selection of patients eligible for treatments may become important for optimization of patient outcomes. TF-targeted PET imaging based on 18 F-radiolabeled active-site inhibited versions of the TF natural ligand coagulation factor VII ( 18 F-ASIS) has in preclinical models convincingly demonstrated its use for noninvasive quantitative measurements of TF expression in tumor tissue. 18 F-ASIS PET imaging thus has the potential to act as a diagnostic companion for TF-targeted therapies in the clinical setting. Methods: In this first-in-humans trial, we included 10 cancer patients (4 pancreatic, 3 breast, 2 lung, and 1 cervical cancer) for 18 F-ASIS PET imaging. The mean and SD of administered 18 F-ASIS activity was 157 ± 35 MBq (range, 93-198 MBq). PET/CT was performed after 1, 2, and 4 h. The primary objectives were to establish the safety, biodistribution, pharmacokinetics, and dosimetry of 18 F-ASIS. Secondary objectives included quantitative measurements of SUVs in tumor tissue with PET and evaluation of the correlation (Pearson correlation) between tumor SUV max and ex vivo TF expression in tumor tissue. Results: Administration of 18 F-ASIS was safe, and no adverse events were observed. No clinically significant changes in vital signs, electrocardiograms, or blood parameters were observed after injection of 18 F-ASIS. Mean 18 F-ASIS plasma half-life was 3.2 ± 0.6 h, and the radiotracer was predominantly excreted in the urine. For injection activity of 200 MBq of 18 F-ASIS, effective whole-body dose was 4 mSv and no prohibitive organ-specific absorbed doses were found. Heterogeneous radiotracer uptake was observed across patients and within tumors. We found a trend of a positive correlation between tumor SUV max and ex vivo TF expression ( r = 0.84, P = 0.08, n = 5). Conclusion: 18 F-ASIS can be safely administered to cancer patients for PET imaging of TF expression in tumors. The trial marks the first test of a TF-targeted PET radiotracer in humans (first-in-class). The findings represent important first steps toward clinical implementation of 18 F-ASIS PET imaging of TF expression.
(© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze: MEDLINE
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