RT Journal Article
SR Electronic
T1 First-in-Humans PET Imaging of Tissue Factor in Patients with Primary and Metastatic Cancers Using <sup>18</sup>F-labeled Active-Site Inhibited Factor VII (<sup>18</sup>F-ASIS): Potential as Companion Diagnostic
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1871
OP 1879
DO 10.2967/jnumed.122.264068
VO 63
IS 12
A1 Loft, Mathias
A1 Christensen, Camilla
A1 Clausen, Malene M.
A1 Carlsen, Esben A.
A1 Hansen, Carsten P.
A1 Kroman, Niels
A1 Langer, Seppo W.
A1 Høgdall, Claus
A1 Madsen, Jacob
A1 Gillings, Nic
A1 Nielsen, Carsten H.
A1 Klausen, Thomas L.
A1 Holm, Søren
A1 Loft, Annika
A1 Berthelsen, Anne K.
A1 Kjaer, Andreas
YR 2022
UL http://jnm.snmjournals.org/content/63/12/1871.abstract
AB 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 18F-radiolabeled active-site inhibited versions of the TF natural ligand coagulation factor VII (18F-ASIS) has in preclinical models convincingly demonstrated its use for noninvasive quantitative measurements of TF expression in tumor tissue. 18F-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 18F-ASIS PET imaging. The mean and SD of administered 18F-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 18F-ASIS. Secondary objectives included quantitative measurements of SUVs in tumor tissue with PET and evaluation of the correlation (Pearson correlation) between tumor SUVmax and ex vivo TF expression in tumor tissue. Results: Administration of 18F-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 18F-ASIS. Mean 18F-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 18F-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 SUVmax and ex vivo TF expression (r = 0.84, P = 0.08, n = 5). Conclusion: 18F-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 18F-ASIS PET imaging of TF expression.