Phase I Clinical Evaluation of Designed Ankyrin Repeat Protein [ 99m Tc]Tc(CO) 3 -(HE) 3 -Ec1 for Visualization of EpCAM-Expressing Lung Cancer.

Simple Summary: The presented article is devoted to the study of the safety, biodistribution and absorbed doses of a new radiopharmaceutical for diagnostics and evaluation of the treatment efficiency of tumors with hyperexpression of epithelial cell adhesion molecules by single-photon emission computed tomography. The results of the study showed the safety and tolerability of [99mTc]Tc(CO)3-(HE)3-Ec1 in patients with lung tumors. The absorbed dose values for [99mTc]Tc(CO)3-(HE)3-Ec1 SPECT are also within the acceptable limits. Also, [99mTc]Tc(CO)3-(HE)3-Ec1 SPECT showed primary diagnostic efficiency in visualizing tumors with EpCAM expression and regional metastases. The promising use of [99mTc]Tc(CO)3-(HE)3-Ec1 will allow the selection of patients for targeted immunotherapy of tumors and evaluation of the efficiency of such treatment. 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 99mTc-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 [99mTc]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 [99mTc]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 [99mTc]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 [99mTc]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 [99mTc]Tc(CO)3-(HE)3-Ec1 in the small and large intestines, pancreas and thyroid. According to the SPECT/CT, accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 in the lung tumor was found in all patients included in the study. Intensive accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 was also noted in regional metastases. [99mTc]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. [ABSTRACT FROM AUTHOR]