Minerva Imaging reports the first-in-human PET imaging of Tissue Factor together with the Cluster for Molecular Imaging, University of Copenhagen and Rigshospitalet. The project was initiated as part of an Innovation Fund Denmark funded project and the development and preclinical evaluation was published in 2015 and 2016. The reporting of the clinical phase I data represents a major milestone and highlights the potential of using 18F-ASIS as a companion diagnostic to guide Tissue Factor directed therapies. 

Tissue factor (TF) is a transmembrane glycoprotein and is upregulated in many solid tumors. The expression is linked to tumor angiogenesis, tumor growth, metastasis, and correlates with a poor overall survival in multiple indications. Altogether this makes TF an emerging oncological target and the first antibody drug conjugate directed at TF was approved in 2021 by the FDA (1).

TF-targeted PET imaging has in preclinical models demonstrated its use for non-invasive quantitative measurements of TF expression in tumor tissue. We developed a 18F-labeled PET tracer based on active site inactivated factor VII (ASIS) that binds to TF with nanomolar affinity as reported by Erlandsson et al. 2015 (2).The subsequent preclinical evaluation was published by Nielsen et al. in 2016 demonstrating specific imaging of TF using 18F-ASIS in xenograft tumor-bearing mice (3). To demonstrate the safety, biodistribution, pharmacokinetics, and dosimetry of 18F -ASIS, a clinical phase I trial was initiated, and the first patient was enrolled early 2019 (4).  

The results, published by Loft et al. in Journal of Nuclear Medicine in 2022, represent the important first steps towards clinical implementation of 18F-ASIS PET imaging of TF expression (5). Administration was safe, no adverse events reported, and patient dosimetry calculations yielded a low radiation exposure. These first clinical data show a good correlation between PET tumor uptake and ex vivo expression of tissue factor of tumor biopsies. This highlights the potential of 18F-ASIS as a companion PET diagnostic tool for identification of patients eligible for tissue factor targeted therapies.  

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This overview reflects all the efforts to bring a new diagnostic from bench to bedside originating from a project funded by Innovation Fund Denmark.  

Reference: 
  1. Genmab/Seagen product page for TIVDAK
  2. Erlandsson et al. 2015 – Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)
  3. Nielsen et al. 2016 – Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site–Inhibited Factor VII
  4. Clinicaltrial.gov – 18F-ASIS PET/CT Imaging of Tissue Factor Expression In Patients With Primary and Metastastic Cancer
  5. Loft et al. 2022 – First-in-Human PET Imaging of Tissue Factor in Patients with Primary and Metastatic Cancers Using 18F-labeled Active-Site Inhibited Factor VII (18F-ASIS): Potential as Companion Diagnostic