The paper presents the procedure for planning an experiment to create standard sets of reagents for a technetium-99m generator based on glucose derivatives. All stages are presented from researching the required quantities of a substance, a reducing agent, a stabilizer and auxiliary components to developing lyophilized kits and conducting quality control. The radiochemical purity of radiopharmaceuticals prepared on the basis of the developed kits ranged from 90.0 to 99.0%. We also showed the functional suitability of the developed preparations on C57B1/6j mice with an implanted malignant tumor -Lewis lung carcinoma. open Scientific RepoRtS | (2020) 10:5121 | https://doi.org/10.1038/s41598-020-61707-7 www.nature.com/scientificreports www.nature.com/scientificreports/ 0.2 Pa and a condenser temperature of −50 °C for at least 24 h, including 4 h of drying in the upper chamber. For the radiolabeling 4 mL of sodium pertechnetate solution [ 99m Tc] with an activity of 1.0 GBq was added to the obtained lyophilized samples and incubated at room temperature for 30 min. Radiochemical purity (RCP) control and the formation of the complex were monitored by TLC. D-glucosamine labeling. Preparation of lyophilizates of D-glucosamine substances was carried out as follows: 1 mL of a solution containing 20 mg of the glucose derivative, 0.140 mg of tin chloride and 200 μl of hydrochloric acid with a concentration of 0.05 mole was placed in a 10 mL vial. The vials without prior freezing were applied to a freeze-dryer at a pressure of 0.2 Pa and a condenser temperature of −50 °C for at least 24 h, including 4 h of drying in the upper chamber. For the radiolabeling 4 mL of sodium pertechnetate solution [ 99m Tc] with an activity of 1.0 GBq was added to the obtained lyophilized samples and incubated at room temperature for 30 min. Radiochemical purity (RCP) control and the formation of the complex were monitored by TLC. Scientific RepoRtS | (2020) 10:5121 | https://doi.www.nature.com/scientificreports www.nature.com/scientificreports/ particular, high-performance liquid chromatography (HPLC) are most frequently used for their determination 16 and for semiquantitative determination -thin-layer chromatography 17 .In our experiments, a high-pressure liquid chromatograph "Agilent 1200" with a refractometric and UV detectors and two types of columns ZORBAX NH2 and ZORBAX SB-C18 using different elution modes.As shown by our research method 1 using a UV detector, ZORBAX SB-C18 columns and gradient elution mode cannot be applied to preparations based on 5-thio-D-glucose and 1-thio-D-glucose, i.e. ascorbic acid, which in this mode of determination is not separated from the main substance and significantly increases the Name of the parameter RP "5-thio-Dglucose, 99m Тс" RP "1-thio-Dglucose, 99m Тс" RP «"Dglucosamine, 99m Тс" Volume of mixture in 1 flask Not more than 1 ml Not more than 1 ml Not more than 1 ml Scientific RepoRtS | (2020) 10:5121 | https://doi.
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.
The subject of this paper is to explore the possibility to obtain 99m Tc from activation of 98 Mo, using the TRIGA Mark II low flux research reactor (Vienna, Austria). Irradiation of both natural and enriched in 98 Mo molybdenum oxides was compared. Aims of this work included the determination of neutron fluxes and 98 Mo(n, c) 99 Mo reaction effective cross section in the TRIGA Mark II reactor irradiation channels, calculation of 99 Mo specific activities, determination of optimal irradiation conditions for the subsequent 99m Tc separation from MoO 3 targets using concentrating technologies.
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.
The efficacy of a new radionuclide, thallium-199 for myocardial scintigraphy was compared with conventional thallium-201 imaging. Owing to the short half-life of thallium-199 (7.4 hours), when the injected dose of thallium-199 was increased to 200 MBq, the total dose reaching the critical organs was 3.6-15.5 times lower than with conventional nuclide, thallium-201. Studies were performed in a total of 177 patients. The patients were divided into two groups(a) 17 patients with acute myocardial infarction and (b) 160 patients undergoing coronary angiography: 55 patients with no significant coronary artery disease and 105 patients with coronary disease. The sensitivity of the test was 92% with a specificity of 82% and overall predictive accuracy of 84%. Myocardial images obtained with low and high energy collimators have similar predictive accuracy. Perfusion defects were detected more frequently with increasing severity of angina. Myocardial infarction was characterized by persistent defects and myocardial ischaemia by redistribution of thallium. Thallium-199 myocardial scintigraphy performed at rest can be used for the diagnosis of acute myocardial infarction and for the determination of infarct site and extent. Thallium-199 is a new myocardial imaging agent, with a predictive accuracy for the diagnosis of coronary artery disease similar to thallium-201, but a significantly reduced total body dose permits repeat studies with a reduced radiation dose for the patient.
Ïðîâåäåíî èññëåäîâàíèå îñòðîé òîêñè÷íîñòè íàíîêîëëîèäíîãî ïðåïàðàòà íà îñíî-âå ãàììà-îêñèäà àëþìèíèÿ, ìå÷åííîãî òåõíåöèåì. Èññëåäîâàíèå îñòðîé òîêñè÷íîñòè ðàäèîôàðìïðåïàðàòà ïðîâåäåíî íà 80 êðûñàõ (40 ñàìöîâ è 40 ñàìîê) è 80 ìûøàõ (40 ñàìöîâ è 40 ñàìîê) ïðè âíóòðèáðþøèííîì è ïîäêîaeíîì ââåäåíèè. Èññëåäîâàíèå îñò-ðîé òîêñè÷íîñòè ïðåïàðàòîâ ïðåäïîëàãàåò îäíîêðàòíîå ââåäåíèå ôàðìàêîëîãè÷åñêîãî âåùåñòâà è äàëüíåéøåå íàáëþäåíèå çà âûaeèâøèìè aeèâîòíûìè â òå÷åíèå 14 ñóò. Íà îñíîâàíèè óñòàíîâëåííûõ ãðàíèö òîêñè÷íîñòè è ñ ó÷åòîì êëàññèôèêàöèè òîêñè÷íîñ-òè ïî Áåðåçîâñêîé È. Â. èçó÷åííûé ïðåïàðàò ìîaeíî óñëîâíî îòíåñòè ê êëàññó óìåðåí-íî òîêñè÷íûõ âåùåñòâ. Äåéñòâèòåëüíûå çíà÷åíèÿ ËÄ 50 íàõîäÿòñÿ â äèàïàçîíå áîëü-øèõ äîç. Êîýôôèöèåíò áåçîïàñíîñòè äëÿ èçó÷åííîãî ïðåïàðàòà ìíîãîêðàòíî ïðåâû-øàåò ìèíèìàëüíîå çíà÷åíèå êîýôôèöèåíòà áåçîïàñíîñòè -100.Êëþ÷åâûå ñëîâà: ðàäèîôàðìïðåïàðàò (ÐÔÏ); ãàììà-îêñèä àëþìèíèÿ; íàíîêîëëîèä; ëèìôàòè÷åñêèé óçåë; îñòðàÿ òîêñè÷íîñòü; êðûñû; ìûøè. ÂÂÅÄÅÍÈÅÑòîðîaeåâûå ëèìôàòè÷åñêèå óçëû (ÑËÓ) ïðåäñòàâ-ëÿþò ñîáîé ïåðâûå ëèìôàòè÷åñêèå óçëû íà ïóòè îòòî-êà ëèìôû îò çëîêà÷åñòâåííîé îïóõîëè. Ïîëàãàþò, ÷òî åñëè ÑËÓ íå ïîðàaeåíû ìåòàñòàòè÷åñêèì ïðîöåññîì, âñå îñòàëüíûå ðåãèîíàðíûå ëèìôîóçëû îñòàþòñÿ èí-òàêòíûìè [9,11]. Ïîâñåìåñòíîå âíåäðåíèå òåõíîëîãèé âûÿâëåíèÿ ÑËÓ ïîçâîëèëî áû óëó÷øèòü êà÷åñòâî aeèç-íè 100 -120 òûñ. ðîññèÿí, êîòîðûì åaeåãîäíî íå ïî ïîêàçàíèÿì âûïîëíÿþò îïåðàòèâíûå âìåøàòåëüñòâà ïî ïîâîäó îíêîëîãè÷åñêîé ïàòîëîãèè [4,8,9,12].  ìèðîâîé ïðàêòèêå íàêîïëåí çíà÷èòåëüíûé îïûò â îò-íîøåíèè ðàäèîíóêëèäíîé âèçóàëèçàöèè ÑËÓ ïðè ìå-ëàíîìå è ðàêå ìîëî÷íîé aeåëåçû. Ïðè îïóõîëÿõ äðóãèõ ëîêàëèçàöèé ýôôåêòèâíîñòü äàííîé ìåòîäèêè èçó÷à-åòñÿ [2,8,9,10,11].Îïòèìàëüíûì ìåòîäîì âûÿâëåíèÿ ÑËÓ ñ÷èòàåòñÿ èñïîëüçîâàíèå ìå÷åííûõ òåõíåöèåì-99ì êîëëîèäíûõ íàíîìàòåðèàëîâ äëÿ ñöèíòèãðàôè÷åñêîãî èëè ðàäèî-ìåòðè÷åñêîãî îïðåäåëåíèÿ ëîêàëèçàöèè óçëà [10]. Ïðè ýòîì îïðåäåëÿþùèì ôàêòîðîì â âûáîðå èíäèêàòîðà ÿâëÿåòñÿ ðàçìåð ðàäèîàêòèâíûõ ÷àñòèö. Òàê, ñîãëàñíî äàííûì [12], êîëëîèä ñ ðàçìåðîì ÷àñòèö ìåíåå 50 íì ìîaeåò íàêàïëèâàòüñÿ íå òîëüêî â ÑËÓ, íî è äðóãèõ óç-ëàõ. ×àñòèöû áîëåå 100 íì ìåäëåííî ìèãðèðóþò ñ ìåñòà èíúåêöèè. Îïòèìàëüíûì äëÿ âûÿâëåíèÿ ÑËÓ áûë ïðèçíàí êîëëîèä ñ ðàçìåðîì ÷àñòèö îò 50 äî 80 íì.Óñòîé÷èâûå êîëëîèäíûå ñîåäèíåíèÿ áûëè ïîëó÷å-íû ïóòåì àäñîðáöèè âîññòàíîâëåííîãî 99m Tc íà ãàì-ìà-îêñèäå àëþìèíèÿ [6, 7]. Ïðè ýòîì âåëè÷èíà àä-ñîðáöèè ðàäèîíóêëèäà íà ïîâåðõíîñòè îêñèäà ïðåâû-øàåò 80 %. Îñíîâíûìè ïðåäïîñûëêàìè äëÿ èñïîëüçî-âàíèÿ íàíîðàçìåðíûõ ïîðîøêîâ ãàììà-îêñèäà Al 2 O 3 â êà÷åñòâå "íîñèòåëÿ» ìåòêè 99m Òñ ÿâëÿåòñÿ åãî íèçêàÿ òîêñè÷íîñòü â ñî÷åòàíèè ñ õîðîøèìè àäñîðáöèîííû-ìè ñâîéñòâàìè, äîñòóïíîñòüþ è íèçêîé ñòîèìîñòüþ. Ñëåäóåò îòìåòèòü, ÷òî êîðîòêîaeèâóùèé òåõíåöèé-99ì ÿâëÿåòñÿ íàèáîëåå âîñòðåáîâàííûì ðàäèîíóêëèäîì äëÿ ïðîâåäåíèÿ äèàãíîñòè÷åñêèõ èññëåäîâàíèé ïðàê-òè÷åñêè âî âñåõ îáëàñòÿõ ìåäèöèíû. Ðàäèîôàðìïðåïà-ðàòû (ÐÔÏ) íà åãî îñíîâå èñïîëüçóþòñÿ áîëåå ÷åì â 87 % âñåõ ðàäèîíóêëèäíûõ èññëåäîâàíèé, ïðîâîäè-ìûõ ñ öåëüþ âûÿâëåíèÿ ðàçëè÷íûõ çàáîëåâàíèé è îöåíêè ñîñòîÿíèÿ aeèâûõ ñèñòåì. Ýòî, â ïåðâóþ î÷å-ðåäü...
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