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.

Non-invasive radionuclide imaging of human epidermal growth factor receptor type 2 (HER2) expression in breast, gastroesophageal, and ovarian cancers may stratify patients for treatment using HER2-targeted therapeutics. Designed ankyrin repeat proteins (DARPins) are a promising type of targeting probe for radionuclide imaging. In clinical studies, the DARPin [^99mTc]Tc-(HE)₃-G3 labeled using a peptide-based chelator His-Glu-His-Glu-His-Glu ((HE)₃), provided clear imaging of HER2 expressing breast cancer 2–4 h after injection. The goal of this study was to evaluate if the use of cysteine-containing peptide-based chelators Glu-Glu-Glu-Cys (E₃C), Gly-Gly-Gly-Cys (G₃C), and Gly-Gly-Gly-Ser-Cys connected via a (Gly-Gly-Gly-Ser)₃-linker (designated as G3-(G₃S)₃C) would further improve the contrast of imaging using ^99mTc-labeled derivatives of G3. The labeling of the new variants of G3 provided a radiochemical yield of over 95%. Labeled G3 variants bound specifically to human HER2-expressing cancer cell lines with affinities in the range of 1.9–5 nM. Biodistribution of [^99mTc]Tc-G3-G₃C, [^99mTc]Tc-G3-(G₃S)₃C, and [^99mTc]Tc-G3-E₃C in mice was compared with the biodistribution of [^99mTc]Tc-(HE)₃-G3. It was found that the novel variants provide specific accumulation in HER2-expressing human xenografts and enable discrimination between tumors with high and low HER2 expression. However, [^99mTc]Tc-(HE)₃-G3 provided better contrast between tumors and the most frequent metastatic sites of HER2-expressing cancers and is therefore more suitable for clinical applications.

This review discusses a relatively new class of targeted molecules that is being actively studied for radionuclide diagnosis and treatment of malignancies. The full-size antibodies used so far have non-optimal pharmacological properties, slow distribution in the body, poor penetration into the tissue and kidney excretion, and high immunogenicity, which significantly complicates their use in clinical practice. Over the past decade, a new class of targeted molecules, called “non-immunoglobulin scaffolds” have become popular; they have all the requirements for optimal delivery of a radionuclide to tumor cells. Scaffolds usually are smaller in size in comparison with antibodies, but they are larger than peptides, and are characterized by high affinity and optimal biochemical, biophysical, biological, and economic features. The advantages of such proteins are their stable structure, good penetration into tissues, the possibility of additional functionalization and expression in the bacterial system, which ensures low production costs.The results of preclinical and clinical studies for diagnosis of malignancies using such proteins as affibody, adnectin, DARPins, etc., have demonstrated their high specificity, affinity, good tolerance and low immunogenicity.

В обзоре литературы представлены данные, касающиеся одного из перспективных направлений таргетной терапии в современной онкологии, получившего название «радиоиммунотерапия». Особое внимание уделяется изучению возможности клинического использования данного вида системного лечения для пациентов как с онкогематологическими заболеваниями, так и с солидными опухолями.

Purpose of the study: to present current data regarding challenges in treatment of castration-resistant prostate cancer (CRPC) and the relationship between CRPC and the expression of prostate-specific membrane antigen (psma).Material and Methods. The search for relevant sources was carried out in the Pubmed, elibrary, Medline databases. The review included 43 publications, most of which were published over the past 5 years.Results. Currently, prostate cancer (PC) is one of the most common cancers in men. Moreover, over time, most patients develop resistance to therapy, which significantly worsens the prognosis of the disease. Psma is one of the molecular markers of prostate cancer; a number of studies have demonstrated a direct correlation between the level of psma expression and the tumor grade, stage and aggressiveness. Numerous studies indicate that psma represents an excellent target for radionuclide therapy of prostate cancer. ⁶⁸Ga or ¹⁸F-psma Pet/Ct is the most common method for diagnosing PC. It should be noted that modern trends in the development of nuclear medicine are closely related to theranostics; therefore, the creation of highly specific theranostic pairs for diagnosis and subsequent therapy of malignant tumors is of great significance. The data obtained indicate that ¹⁷⁷lu demonstrates the most optimal radiation and physical characteristics for therapeutic radionuclides, while psma-617 is one of the most studied ligands for radionuclide therapy.Conclusion. Currently, there are several studies covering radionuclide therapy with various psmacompounds labeled with ¹⁷⁷lu. Radionuclide therapy with ¹⁷⁷lu-psma has been shown to be recommended for patients with metastatic CRPC, who have no benefits from alternative therapies or have contraindications to them.

Introduction. The purpose of this study was to evaluate the feasibility of using 99mTc-TG SPECT in the detection and staging of malignant lymphoma.Materials and methods.Fifteen patients with newly diagnosed malignant lymphoma underwent 99mTc-TG SPECT. Six patients had Hodgkin’s lymphoma and 9 patients had aggressive forms of non-Hodgkin’s lymphoma (NHL): diffuse large B-cell lymphoma (7 cases), B-cell follicular lymphoma (1 case), and lymphoma from B cells in the marginal zone (1 case). Stage IIA was diagnosed in 5 patients, stage IIB in 1, stage IIIA in 1, stage IVA in 4 and stage IVB in 4 patients.Results.Pathological 99mTc-TG uptake in lymph nodes was observed in 14 (93 %) of the 15 patients. In one patient, the enlarged submandibular lymph node (16 mm in size) detected by CT was not visualized by 99mTc-TG SPECT. This false-negative result was likely to be associated with increased accumulation of 99mTc-TG in the oropharyngeal region. There were difficulties in the visualization of paratracheal, para-aortic and paracardial lymph nodes. These difficulties were associated with a high blood background activity, which persisted even 4 hours after intravenous injection of 99mTc-TG. Software-based SPECT and CT image fusion allowed visualization of these lymph nodes. The pathological 99mTc-TG accumulation in axillary, supraclavicular, infraclavicular and cervical lymph nodes was observed most often. Extranodal involvement was seen in 9 patients. 99mTc-TG SPECT identified extranodal hypermetabolic lesions in 7 (78 %) of these patients. In one patient, hypermetabolic lesion in the lung detected by 99mTc-TG SPECT was not detected on CT image. CT identified bone marrow involvement in the pelvic and scapula in 1 patient. The use of 99mTc-TG SPECT allowed the visualization of hypermetabolic bone tissue lesions in this patient (Figure 4). In addition, in a patient with intact bone tissue on CT, 99mTc-TG SPECT detected hypermetabolic lesions in the iliac bone.Conclusion.99mTc-1-Thio-D-glucose demonstrated increased uptake in nodal and extranodal sites of lymphoma. The results indicate that SPECT with 99mTc-1-Thio-D-glucose is a feasible and useful tool in the detection and staging malignant lymphoma.