Phase I Clinical Evaluation of Designed Ankyrin Repeat Protein [99mTc]Tc(CO)3-(HE)3-Ec1 for Visualization of EpCAM-Expressing Lung Cancer
A high level of EpCAM overexpression in lung cancer makes this protein a promising target for targeted therapy. Radionuclide visualization of EpCAM expression would facilitate the selection of patients potentially benefiting from such treatment. Single-photon computed tomography (SPECT) using <sup>99m</sup>Tc-labeled engineered scaffold protein DARPin Ec1 has shown its effectiveness in imaging tumors with overexpression of EpCAM in preclinical studies, providing high contrast just a few hours after injection. This first-in-human study aimed to evaluate the safety and distribution of [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-(HE)<sub>3</sub>-Ec1 in patients with primary lung cancer. Twelve lung cancer patients were injected with 300.7 ± 103.2 MBq of [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-(HE)<sub>3</sub>-Ec1. Whole-body planar imaging (at 2, 4, 6 and 24 h after injection) and SPECT/CT of the lung (at 2, 4, and 6 h) were performed. The patients' vital signs and possible side effects were monitored up to 7 days after injection. The patients tolerated the injection of [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-(HE)<sub>3</sub>-Ec1 well, and their somatic condition remained normal during the entire follow-up period. There were no abnormalities in blood and urine tests after injection of [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-(HE)<sub>3</sub>-Ec1. The highest absorbed doses were in the kidneys, liver, pancreas, thyroid, gallbladder wall, and adrenals. There was also a relatively high accumulation of [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-(HE)<sub>3</sub>-Ec1 in the small and large intestines, pancreas and thyroid. According to the SPECT/CT, accumulation of [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-(HE)<sub>3</sub>-Ec1 in the lung tumor was found in all patients included in the study. Intensive accumulation of [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-(HE)<sub>3</sub>-Ec1 was also noted in regional metastases. [<sup>99m</sup>Tc]Tc(CO)<sub>3</sub>-(HE)<sub>3</sub>-Ec1 can potentially be considered a diagnostic tracer for imaging EpCAM expression in lung cancer patients and other tumors with overexpression of EpCAM.
Authors
- А. A. Medvedeva (ORCID: https://orcid.org/0000-0003-2113-6436)
- Anzhelika Vorobyeva (ORCID: https://orcid.org/0000-0002-4778-3909)
- Л. А. Таширева (ORCID: https://orcid.org/0000-0003-2061-8417)
- Anna Orlova (ORCID: https://orcid.org/0000-0001-6120-2683)
- Anastasia Rybina
- Alexey Schulga (ORCID: https://orcid.org/0000-0003-3425-0828)
- A.S. Fominykh (ORCID: https://orcid.org/0009-0000-0645-8918)
- Sergey M. Deyev (ORCID: https://orcid.org/0000-0002-3952-0631)
- Е. В. Коновалова (ORCID: https://orcid.org/0000-0002-4187-376X)
- В. И. Чернов (ORCID: https://orcid.org/0000-0002-5524-9546)
- Vladimir Tolmachev (ORCID: https://orcid.org/0000-0002-6122-1734)
- Ruslan Varvashenya (ORCID: https://orcid.org/0009-0002-4282-3198)
- Olga Bragina (ORCID: https://orcid.org/0000-0001-5281-7758)
- M. S. Larkina (ORCID: https://orcid.org/0000-0003-1176-2441)
- Roman Zelchan
- Elizaveta Mishina
Institutions
- Uppsala University (SE)
- Russian Academy of Sciences (RU)
- National Research Tomsk State University (RU)
- Siberian State Medical University (RU)
- Tomsk Polytechnic University (RU)
- Institute of Bioorganic Chemistry (RU)
- Tomsk National Research Medical Center (RU)
Publication Details
- Journal
- Cancers
- Published
- 2024-08-10
- DOI
- https://doi.org/10.3390/cancers16162815
- Citations
- 12
- Primary Topic
- Medical Imaging Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 4.85
Funders
- Ministry of Science and Higher Education of the Russian Federation