Zelchan, Roman, Chernov, Vladimir, Medvedeva, Anna, Rybina, Anastasia, Bragina, Olga, Mishina, Elizaveta, Larkina, Mariia, Varvashenya, Ruslan, Fominykh, Anastasia, Schulga, Alexey, Konovalova, Elena, Vorobyeva, Anzhelika, Orlova, Anna, Tashireva, Liubov, Deyev, Sergey M., Tolmachev, Vladimir, Zelchan, Roman, Chernov, Vladimir, Medvedeva, Anna, Rybina, Anastasia, Bragina, Olga, Mishina, Elizaveta, Larkina, Mariia, Varvashenya, Ruslan, Fominykh, Anastasia, Schulga, Alexey, Konovalova, Elena, Vorobyeva, Anzhelika, Orlova, Anna, Tashireva, Liubov, Deyev, Sergey M., and Tolmachev, Vladimir
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 Tc-99m-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 [Tc-99m]Tc(CO)(3)-(HE)(3)-Ec1 in patients with primary lung cancer. Twelve lung cancer patients were injected with 300.7 +/- 103.2 MBq of [Tc-99m]Tc(CO)(3)-(HE)(3)-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 [Tc-99m]Tc(CO)(3)-(HE)(3)-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 [Tc-99m]Tc(CO)(3)-(HE)(3)-Ec1. The highest absorbed doses were in the kidneys, liver, pancreas, thyroid, gallbladder wall, and adrenals. There was also a relatively high accumulation of [Tc-99m]Tc(CO)(3)-(HE)(3)-Ec1 in the small and large intestines, pancreas and thyroid. According to the SPECT/CT, accumulation of [Tc-99m]Tc(CO)(3)-(HE)(3)-Ec1 in the lung tumor was found in all patients included in the study. Intensive accumulation of [Tc-99m]Tc(CO)(3)-(HE)(3)-Ec1 was also noted in regional metastases. [Tc-99m]Tc(CO)(3)-(HE)(3)-Ec1 can potentially be considered a diagnostic tracer for imaging EpCAM expression in lung cancer patients and other tumors with overexpression of EpCAM.