Radionuclide molecular imaging of human epidermal growth factor type 2 (HER2) expression may enable a non-invasive discrimination between HER2-positive and HER2-negative breast cancers for stratification of patients for HER2-targeted treatments. DARPin G3 is a small (molecular weigh 14 kDa) scaffold protein with picomolar affinity to HER2. The aim of this firstin-human study was to evaluate the safety, biodistribution and dosimetry of 99m Tc-(HE)3-G3.Methods. Three cohorts of patients with primary breast cancer (each including at least 4 patients with HER2-negative and 5 patients with HER2-positive tumors) were injected with either 1000, 2000 or 3000 µg of 99m Tc-(HE)3-G3 (287±170 MBq). Whole-body planar imaging followed by SPECT was performed at 2, 4, 6 and 24 h after injection. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection.Results. All injections were well tolerated. No side effects were observed. The results of blood and urine analyses did not differ before and after studies. 99m Tc-(HE)3-G3 cleared rapidly from the blood. The highest uptake was detected in the kidneys and liver followed by the lungs, breasts and small intestinal content. The hepatic uptake after injecting with 2000 or 3000 µg was significantly (p<0.05) lower than the uptake after injecting with 1000 µg. Effective doses did not differ significantly between cohorts (average 0.011± 0.004 mSv/MBq). Tumor-to-contralateral site ratios for HER-positive tumors were significantly (p< 0.05) higher than for HER2-negative at 2 and 4 h after injection. Conclusions.Imaging of HER2 expression using 99m Tc-(HE)3-G3 is safe, well-tolerated and provides a low absorbed dose burden on patients. This imaging enables discerning HER2-positive and HER2-negative breast cancer. Phase I study data justifies further clinical development of 99m Tc-(HE)3-G3.

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The purpose of the study was a comparative research in the possibility of using the radiopharmaceuticals 99m Tc-Al 2 O 3 and 99m Tc-Nanocis for visualizing sentinel lymph nodes. The measurement of the sizes of 99m-Al 2 O 3 and 99m-Nanocis colloidal particles was performed in seven series of radiopharmaceuticals. The pharmacokinetics of 99m-Al 2 O 3 and 99m-Nanocis was researched on 50 white male rats. The possibility of the use of 99m-Al 2 O 3 and 99m-Nanocis for lymphoscintigraphy was studied in the experiments on 12 white male rats. The average dynamic diameter of the sol particle was 52-77 nm for 99m-Al 2 O 3 and 16.7-24.5 nm for 99m-Nanocis. Radiopharmaceuticals accumulated in the inguinal lymph node in 1 hour after administration; the average uptake of 99m Tc-Al 2 O 3 was 8.6% in it, and the accumulation of 99m Tc-Nanocis was significantly lower-1.8% (p < 0.05). In all study points the average uptake of 99m Tc-Al 2 O 3 in the lymph node was significantly higher than 99m Tc-Nanocis accumulation. The results of dynamic scintigraphic studies in rats showed that 99m Tc-Al 2 O 3 and 99m Tc-Nanocis actively accumulated into the lymphatic system. By using 99m Tc-Al 2 O 3 inguinal lymph node was determined in 5 minutes after injection and clearly visualized in all the animals in the 15th minute, when the accumulation became more than 1% of the administered dose. Further observation indicated that the 99m Tc-Al 2 O 3 accumulation reached a plateau in a lymph node (average 10.5%) during 2-hour study and then its accumulation remained practically at the same level, slightly increasing to 12% in 24 hours. In case of 99m Tc-Nanocis inguinal lymph node was visualized in all animals for 15 min when it was accumulated on the average 1.03% of the administered dose. Plateau of 99m Tc-Nanocis accumulation in the lymph node (average 2.05%) occurred after 2 hours of the study and remained almost on the same level (in average 2.3%) for 24 hours. Thus, the experimental study of a new domestic radiopharmaceutical showed that the 99m Tc-Al 2 O 3 accumulates actively in the lymph nodes several times as compared to the imported analogue and its practical application will facilitate intraoperative identification of sentinel lymph nodes.

Abstract. Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99m Tc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99m Tc-1-thio-Dglucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99m Tc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of 99m Tc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512 512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99m Tc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of 99m Tc-1-thio-D-glucose at the tumor site. The accumulation of 99m Tc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99m Tc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99m Tc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

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Despite the high efficiency of the use of 18F-FDG PET in the diagnosis, staging, monitoring and prognosis of treatment of lymphomas, the use of this method in our country is limited due to the high cost and the insufficient number of PET-centers. In this regard, it seems relevant to conduct research aimed at using known and developing original radiopharmaceuticals for lymphoma imaging with single-photon emission computed tomography (SPECT). In this review, the main radiopharmaceuticals (67Ga-citrate, 201Tl, 199Tl, 99mTc-methoxy-isobutyl-isonitrile, 99mTc-tetrofosmin, 111In-octreotide), which are possible for SPECT lymphoma imaging are shown. Also mechanisms of their action, the possibility of their using for various morphological variants of lymphomas and localizations of the lesion are described. In addition, the results of the use of an innovative radiopharmaceutical based on glucose - 99mTc-1-thio-D-glucose, which is promising for diagnostics, staging and monitoring of lymphoproliferative diseases, are presented.