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

Qianna Wang; Qianqian Gan; Yuhao Jiang; Di Xiao; Xiaoliang Chen; Junbo Zhang

doi:10.1021/acsptsci.3c00146

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

ACS Pharmacol Transl Sci. 2023 Oct 11;6(11):1681-1691. doi: 10.1021/acsptsci.3c00146. eCollection 2023 Nov 10.

Authors

Qianna Wang¹, Qianqian Gan^{1

2}, Yuhao Jiang¹, Di Xiao¹, Xiaoliang Chen^{3

4}, Junbo Zhang¹

Affiliations

¹ Key Laboratory of Radiopharmaceuticals of the Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
² Department of Nuclear Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
³ Department of Nuclear Medicine, Chongqing University Cancer Hospital, Chongqing 400030, P.R. China.
⁴ Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China.

PMID: 37974617
PMCID: PMC10644395 (available on 2024-10-11)
DOI: 10.1021/acsptsci.3c00146

Abstract

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.