The Preparation and Execution of Exploratory Human Studies on Novel 99m Tc-Labeled Glucosamine Derivatives Containing Different Phenyl Isonitriles as Promising Tumor Imaging Agents.

As the "molecule of the century", 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]FDG) is a radioactive 18 F-labeled glucose derivative with a wide range of applications for positron emission tomography (PET) imaging. Single photon emission computed tomography (SPECT) imaging is widely used, but there is no clinical probe comparable to [ 18 F]FDG. In our previous work, [ 99m Tc]Tc-CN5DG and [ 99m Tc]Tc-CN7DG were successfully developed and achieved high-quality SPECT images. However, they still have the disadvantage of low tumor uptake and/or high uptake by nontarget organs. To develop novel tumor imaging agents with high tumor uptake and excellent tumor/nontarget ratios, in this study, starting from d-glucosamine hydrochloride, four phenyl group-containing isonitrile ligands were designed, synthesized, and radiolabeled with 99m Tc. All the complexes had high radiochemical purity and good hydrophilicity and stability. Biodistribution experiments showed that [ 99m Tc]Tc- L4 (i.e., [ 99m Tc]Tc-CNMBDG) had the highest tumor uptake and tumor/background ratios among the four probes. In SPECT imaging studies, the tumor detected by [ 99m Tc]Tc- L4 was more clearly visible than that of [ 99m Tc]Tc-CN7DG because of the inappreciable interference from abdominal uptake. Preliminary clinical studies of [ 99m Tc]Tc- L4 have been conducted and successfully showed the lesion location in a patient with non-small-cell lung cancer. In summary, [ 99m Tc]Tc- L4 is expected to be a promising tumor SPECT imaging agent.