99mTc-labeled monosaccharide kits: development methods and quality control

Abstract

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.

Phase I Clinical Trial Using [99mTc]Tc-1-thio-D-glucose for Diagnosis of Lymphoma Patients

“…Labeling of [ 99m Tc]Tc-TG was performed in aseptic conditions using a single-vial kit described earlier [11]. Briefly, kits containing 2.5 mg of the glucose derivative, 0.21 mg of tin chloride dihydrate and 0.5 mg of ascorbic acid each were prepared in aseptic conditions by freeze-drying (−50 • C, 24 h).…”

“…Further preclinical studies demonstrated that [ 99m Tc]Tc-TG does not have any acute or cumulative toxicity and is not allergenic. Accumulation of [ 99m Tc]Tc-TG in tumor cells, including the RMA lymphoma cell line, was demonstrated in vivo and in vitro [11,12].…”

“…The secondary objective was to evaluate the possibility of using [ 99m Tc]Tc-TG SPECT/CT for visualizing GLUT expression in the nodal and extranodal lesions of lymphoma patients. In preparation for clinical studies, a single-vial kit for labeling 1-thio-D-glucose and the analytical methods for characterizing the labeled product were developed [11]. Further preclinical studies demonstrated that [ 99m Tc]Tc-TG does not have any acute or cumulative toxicity and is not allergenic.…”

Phase I Trial of ^99mTc-1-Thio-D-glucose for Imaging of Lymphomas

“…Further preclinical studies demonstrated that 99m Tc-TG does not have any acute or cumulative toxicity and is not allergenic. Accumulation of 99m Tc-TG in tumor cells, including the RMA lymphoma cell line, was demonstrated in vivo and in vitro [11,12]. There were three primary objectives of this first-in-human study: firstly, to obtain initial information concerning the safety and tolerability of 99m Tc-TG after a single intravenous injection; secondly, to assess the distribution of 99m Tc-TG in normal tissues and in tumors over time; and thirdly, to evaluate the dosimetry of 99m Tc-TG.…”

“…In preparation for clinical studies, a single-vial kit for labeling 1-thio-D-glucose and the analytical methods for characterizing the labeled product were developed [11]. Further preclinical studies demonstrated that 99m Tc-TG does not have any acute or cumulative toxicity and is not allergenic.…”