Abstract
2884
Introduction: One of the important reasons why so many people die of cancer every year was that cancer was not diagnosed and treated in time. In the early diagnosis of tumor, PET examination plays an important role. As a molecular probe reflecting glucose metabolism in tumor tissue, 18F-FDG was synthesized as early as 1969 and its physiological characteristics were studied. However, the production of F-18 nuclide needs positron cyclotron and advanced shielding site, and the cost and initial investment are huge, which can reach millions of dollars. Moreover, 18F-FDG PET/CT still has some limitations in the diagnosis of gastrointestinal tumors, such as primary hepatocellular carcinoma and mucinous gastric cancer. In 2019, Zeng Wenbin and his colleagues introduced various metal nuclides labeled glucose analogues in detail, including single photon nuclides Tc-99m, In-111 and positron nuclides Cu-64, Ga-68. We believe that Ga-68 is a better metal nuclide than Tc-99m for higher resolution of PET compared with that of SPECT. If we could apply PET tumor imaging with Ga-68 labeled molecular probes in areas of poverty or areas with little number of patients, it will be beneficial to tumor patients there who are critically ill and not suitable for long-distance referral. In 2012, Yang Zhi and his colleagues used Ga-68 to label DOTA-ADG. With microwave reactor, 68Ga-DOTA-ADG with purity higher than 98% could be obtained with 85% labeling efficiency after purification. Compared with DOTA, NOTA is a more suitable chelator for labeling Ga-68 since the ion radius of Ga-68 is small and the thermodynamic stability constant of 68Ga-NOTA is about 10 orders of magnitude higher than that of 68Ga-DOTA. Therefore, we tried to synthesize NOTA-ADG and investigate its biological behaviors.
Methods: NOTA-Amino-DG could be obtained from p-SCN-Bn-NOTA and 2-amino-2-deoxy-D-glucose at room temperature with pH of 9~10 in almost quantitative yield. And the reaction solution could be used for labeling directly. After 68GaCl3 eluent was added to NOTA-Amino-DG solution and the reaction mixture was incubated at room temperature for 5 min, 68Ga-NOTA-ADG could be obtained in radiochemical yield of almost 100%. PET imaging of subcutaneous tumor model mice with gastric cancer, liver cancer, colon cancer and lung cancer was performed with 68Ga-NOTA-ADG and 18F-FDG respectively.
Results: The radiochemical yield of 68Ga-NOTA-ADG was almost 100% after 5 min at room temperature, and the radiochemical purity was above 99%. The product could be used for PET imaging with tumor model mice directly without further purification. ICR mice were used as the research objects, and we found that the distribution of 68Ga-NOTA-ADG for ICR mice in the heart, liver, kidneys and brain was significantly different from that of 18F-FDG. PET imaging of subcutaneous tumor model mice with gastric cancer, liver cancer, colon cancer and lung cancer showed that the uptake of 68Ga-NOTA-ADG in tumor tissue was higher than that in muscle background obviously. 68Ga-NOTA-ADG could perform broad-spectrum tumor imaging and compared with 18F-FDG, had a higher tumor/tissue signal-to-noise ratio. Besides, we prepared a cold kit, with which one could prepare 68Ga-NOTA-ADG quite easily.
Conclusions: Compared with 18F-FDG, the preparation of 68Ga-NOTA-ADG is very flexible, fast and convenient. In the end, we believed that 68Ga-NOTA-ADG could be used as a potential molecular probe in clinic for certain tumors PET imaging and behaving as a complementation to 18F-FDG, eventually enhanced effectiveness of PET in tumor diagnosis.
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