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.

Similar to [¹⁸F]-FDG, [^99mTc]Tc-1-thio-D-glucose ([^99mTc]Tc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of [^99mTc]Tc-TG. Twelve lymphoma patients were injected with 729 ± 102 MBq [^99mTc]Tc-TG. Whole-body planar imaging was performed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients, SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. [^99mTc]Tc-TG injections were well-tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone marrow, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. [^99mTc]Tc-TG SPECT/CT revealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal lesions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using [^99mTc]Tc-TG. Potentially, [^99mTc]Tc-TG can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.

Aim. To study interconnections between epicardial adipose tissue thickness (EATt), parameters of glucose metabolism/insulin, C-reactive protein (hsCRP), serum adipokines and severity of coronary artery disease (CAD) depending on the presence of diabetes mellitus type 2 (DM 2); to determine significant markers of CAD severity in patients with DM 2. Materials and methods. The study involved 106 patients with CAD (m/f 64/42, 60.96.8 years), including patients with DM 2 (group 1, n=35) and non-diabetic patients (group 2, n=71). Severity of CAD was evaluated according to angiography data with calculation of Gensini Score (GS). EATt was assessed via echocardiography. Serum levels of glucose/insulin metabolism parameters, lipid fractions, hsCRP and adipokines were evaluated. Clinical parameters, including GS, did not differ between groups. Results. EAT thickness median was elevated in gr.1 (5.1 mm vs. 4.4 mm in group 2), while adiponectin levels were decreased (6.55 g/ml vs. 7.71 g/ml). Linear regression of body mass index and resistin levels on EATt was revealed in gr.1; in gr.2 EATt linearly increased with waist circumference increment when EATt6 mm. Linear regression of EATt on GS was revealed in gr.1 when EATt8 mm, while linear regression in the whole GS range was obtained for HDL-C and hsCRP levels. Conclusion. Study results demonstrate differences in mechanisms of deposition and functioning of epicardial and abdominal adipose tissue depending on the presence or absence of diabetic status. Patients with DM2 are characterized by the excessive EAT deposition and decrease of serum adiponectin levels compared to non-diabetic patients in the equal conditions. Independent markers of CAD severity in DM 2 are decreased HDL-C and increased hsCRP levels, but not EATt.

Введение. В последние годы наблюдается значительный интерес к созданию радиофармацевтических лекарственных препаратов (РФЛП), меченых 99mTc, на основе низкомолекулярных ингибиторов ПСМА для визуализации опухолей предстательной железы. Цель. Оценка безопасности применения, фармакокинетики и дозиметрических характеристик РФЛП [99мTс]Tc-HYNIC-ПСМА. Материалы и методы. В исследование включено 10 больных раком предстательной железы (РПЖ) T1–4N0–3M0-1 стадий. Радиофармацевтический лекарственный препарат [99mTc]Tc-HYNIC-ПСМА вводился внутривенно болюсно в дозе 649,6 ± 70,7 МБк. Больные находились под динамическим наблюдением в течение 48 ч. после введения РФЛП с контролем лабораторных и клинических данных. Радионуклидное исследование проводилось на гамма-камере Symbia Intevo Bold (Siemens) в режиме Wholebody через 2, 4, 6 и 24 ч. после введения РФЛП, однофотонная эмиссионная компьютерная томография, совмещенная с КТ (ОФЭКТ/КТ) выполнялась через 2 ч. после введения индикатора. По данным постпроцессинговой обработки, анализировался уровень аккумуляции РФЛП в основных органах. Поглощенные дозы вычислялись программой OLINDA/EXM 1.1. Результаты. Было показано, что [99mTc]Tc-HYNIC-ПСМА хорошо переносится пациентами, не было обнаружено патологически значимых изменений клинических лабораторных анализов. Период полувыведения РФЛП из плазмы крови составил 2,7 ч. Дозиметрические исследования показали, что основными критическими органами при использовании изучаемого РФЛП являются почки. Эффективная доза облучения пациентов при однократном внутривенном введении РФЛП составила 0,004 ± 0,0005 мЗв/МБк, а эквивалентная эффективная доза — 0,00748 ± 0,00014 мЗв/МБк. Показано, что ОФЭКТ/КТ с [99mTc]Tc-HYNIC-PSMA позволяет визуализировать ПСМА-позитивные опухоли предстательной железы, регионарные и отдаленные метастазы РПЖ. Заключение. Полученные данные демонстрируют схожесть фармакокинетических параметров и дозовых нагрузок [99mTc]Tc-HYNIC-ПСМА с другими РФЛП на основе ПСМА-лигандов для ОФЭКТ-визуализации. Для оценки диагностической эффективности ОФЭКТ/КТ с [99mTc]Tc-HYNIC-ПСМА необходимо проведение дальнейших клинических исследований.

Background/Objectives: The gastrin-releasing peptide receptor (GRPR) shows high-density expression in prostate cancer (PCa), especially in the early stages of the disease. The introduction of a safe radiotracer for assessing GRPR-expression in PCa may serve as an alternative or complementary tracer to PSMA-directed probes for patients with insufficient PSMA expression. In the present study, the tolerability and safety, biodistribution, and dosimetry of the new GRPR-targeting radiopeptide [^99mTc]Tc-DB8 were investigated for the first time in male PCa patients. A mass escalation study was performed, aiming to improve tumor-to-background contrast and, thereby, to enhance diagnostic accuracy. Methods: Sixteen male patients were enrolled in a single-center diagnostic open-label exploratory Phase I clinical trial. Patients were administered a single intravenous injection of 40, 80, or 120 µg of [^99mTc]Tc-DB8 peptide (n = 5–6) and underwent whole-body planar imaging (anterior and posterior) 2, 4, 6, and 24 h post-injection (pi) and SPECT-CT acquisition 2, 4, and 6 h pi. Results: Administration of [^99mTc]Tc-DB8 was well tolerated at all tested peptide masses. The effective dose did not differ significantly between the injected peptide mass and was 0.005 ± 0.003 mSv/MBq. High activity uptake was observed in the pancreas and kidneys, which 3-fold decreased with an increasing injected peptide mass from 40 to 120 µg. The activity uptake in primary tumors did not differ significantly between cohorts injected with different peptide masses [SUV_max 1.65–9.96]. The tumor-to-muscle ratios increased with time and were the highest for the cohort injected with 120 µg of peptide, 7.2 ± 3.1 (4.64-11-25) at 4 h pi. Conclusions: Single intravenous administration of [^99mTc]Tc-DB8, for visualization of GRPR expression in PCa using SPECT imaging was well tolerated in a peptide mass range of 40–120 µg. An injected peptide mass of 80–120 µg/patient and SPECT acquisition 2–4 h pi were found to be optimal for further clinical studies due to the significantly lower activity accumulation in the pancreas and kidneys.

Introduction. In modern oncology, the identification of sentinel lymph nodes (SLN), the first nodes that stand on the way of malignant tumor metastasis, is of increasing interest. Detection of SLN followed by morphological examination allows personalizing the surgical intervention for early breast cancer, melanoma, head and neck tumors, neoplasms of the cervix and endometrium. Currently, there is an active development of specific radiopharmaceuticals for SLN imaging. Within the framework of the grant from the Federal Target Program "Pharma-2020", an original radiopharmaceutical using gamma aluminum oxide – [^99mТс]-Al₂O₃ was developed. Preclinical studies have been demonstrated its effectiveness and safety. Pharmacokinetic studies of [^99mTc]-Al₂O₃ showed that 24 hours after its subcutaneous administration, about 12 % of the administered dose is accumulated in the SLN, which gives possibility for its detection.Aim. To study the possibility of clinical [^99mTc]-Al₂O₃ using for visualization of SLN in breast, larynx and laryngopharyngeal cancer.Materials and methods. The definition of SLN was carried out in 55 patients with breast cancer and 30 patients with malignant tumors of the larynx and laryngopharynx. The study included peritumoral radiopharmaceutical injection, single-photon emission computed tomography with qualitative and quantitative analysis of the images and radioguided surgery detection of lymph nodes with their subsequent morphological examination.Results and discussion. Clinical studies have shown that radionuclide imaging of SLN using [^99mTc]-Al₂O₃ is characterized by high sensitivity in breast cancer, larynx and laryngopharyngeal cancer patients (94.5 and 90 %, respectively), due to the high-intensity accumulation of this radiopharmaceutical in the lymph nodes. The optimal time point for SPECT and radioguided examination is an interval of 18–20 hours after injection of [^99mTc]-Al₂O₃, which allows visualizing the maximum possible number of lymph nodes with the most optimal level of radioactivity for their detection.Conclusion. Application of radionuclide imaging of SLN with the use of [^99mTc]-Al₂O₃ as a radiopharmaceutical is useful in planning surgical treatment of patients with tumors of the breast, larynx and laryngopharynx to determine the extent of surgery.