As the "molecule of the century", 2-deoxy-2-[18F]fluoro-
d-glucose ([18F]FDG) is a radioactive 18F-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 [18F]FDG. In our previous work, [99mTc]Tc-CN5DG and [99mTc]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 99mTc. All the complexes had high radiochemical purity and good hydrophilicity and stability. Biodistribution experiments showed that [99mTc]Tc-L4 (i.e., [99mTc]Tc-CNMBDG) had the highest
tumor uptake and
tumor/background ratios among the four probes. In SPECT imaging studies, the
tumor detected by [99mTc]Tc-L4 was more clearly visible than that of [99mTc]Tc-CN7DG because of the inappreciable interference from abdominal uptake. Preliminary clinical studies of [99mTc]Tc-L4 have been conducted and successfully showed the lesion location in a patient with
non-small-cell lung cancer. In summary, [99mTc]Tc-L4 is expected to be a promising
tumor SPECT imaging agent.