Evaluation of 99mTc-CN5DG as a broad-spectrum SPECT probe for tumor imaging

Significance 

Nuclear medicine and molecular imaging play an important role in the diagnosis and treatment of cardiovascular diseases and cancers. All over the world, the two main imaging modalities used are Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT). Due to its availability from the 99Mo/99mTc generator and inexpensive cost, 99mTc is the most used nuclide for SPECT. The overall number of SPECT scanners in the whole world are far more than PET scanners. It is therefore necessary that 99mTc labeled glucose derivatives are developed as broad-spectrum SPECT probes for tumor imaging. This has however remained challenging. In addition, for about three decades now 99mTc labeled glucose derivatives for tumor imaging have been studied and none has been approved to be used for tumor diagnosis in clinic. Some preliminary studies have already been conducted in mice bearing A549 tumor xenografts and have shown that 99mTc-CN5DG has the potential to be a powerful SPECT probe for tumor detection.

In order to verify how effective 99mTc-CN5DG is in the detection of other kinds of tumors, Dr. Xuran Zhang, Dr. Qing Ruan, Dr. Yuhao Jiang, Dr. Qianqian Gan and Dr. Junbo Zhang all from the Key Laboratory of Radiopharmaceuticals of Ministry of Education at Beijing Normal University tried to explore the feasibility of 99mTc-CN5DG as a broad-spectrum SPECT probe for tumor imaging and assess its pharmacokinetic properties and stability in vivo.  Their results showed that 99mTc-CN5DG had high tumor/muscle ratios and tumor/blood ratios and the tumors were clearly seen on their corresponding SPECT/CT images. The work is published in Translational Oncology.

The research team evaluated 99mTc-CN5DG in four tumor xenografts models namely human esophageal cancer cells, human colon cancer cells, human glioma cells and human pancreatic cancer cells. They observed that the biodistribution pattern of 99mTc-CN5DG was similar in the four tumor models with high accumulation in the tumors and kidneys. The uptake of 99mTc-CN5DG was found to be higher in human colon cancer, human pancreatic cancer and human esophageal cancer compared to human glioma. In addition, the tumor/blood ratios and tumor/muscle ratios of 99mTc-CN5DG inhuman pancreatic cancer and human esophageal cancer were higher than those in human colon cancer and human glioma.

2 hours after the injection of 99mTc-CN5DG via the tail vein, the gotten three-dimensional whole body SPECT/CT images showed that tumors could be seen clearly in all the four tumor model studies. The bladder and kidney were also seen clearly from the SPECT/CT images. It was also found that the retention time of 99mTc-CN5DG when injected in both the control and tumor were similar. Furthermore, the retention time of 99mTc-CN5DG in blood at 30 min after intravenous injection was also similar to that of the control. 99mTc-CN5DG was noticed to have a fast clearance rate in blood in vivo. The solution of 99mTc-CN5DG was also found to have low toxicity and none of the five mice used in the abnormal toxicity study showed any abnormality or died after 48 hours

In summary, the authors demonstrate successfully that 99mTc-CN5DG has a high tumor uptake, tumor/blood and tumor/muscle ratios in different kinds of tumor models. They also showed that 99mTc-CN5DG was stable in blood and tumors in vivo and rapidly cleared from blood. These new findings have confirmed that 99mTc-CN5DG can be used as a promising broad-spectrum tumor-imaging agent with a potential for clinical translation.

Evaluation of 99mTc-CN5DG as a broad-spectrum SPECT probe for tumor imaging - Medicine Innovates

About the author

Junbo Zhang received his Bachelor degree, Master degree and PhD degree at Department of Chemistry of Beijing Normal University. Now he is a professor and vice dean of College of Chemistry of Beijing Normal University. His research focuses on the design, synthesis and biological evaluation of novel radiolabelled compounds as heart, brain, tumor and infection imaging agents. As the first author or corresponding author, he has authored more than 60 peer-reviewed publications and has applied/issued more than 40 patents. He has hosted 6 projects of National Natural Science Foundation of China and 1 major project of Beijing Municipal Science and Technology Commission.

He acted as the Executive Guest Editor of Current Pharmaceutical Design and Current Medicinal Chemistry. Currently, he is the Vice President of the Society of Radiopharmaceutical of Chinese Nuclear Society and the Vice secretary-general of the Society of Nuclear and Radiochemistry of Chinese Nuclear Society.

Reference

Zhang X, Ruan Q, Jiang Y, Gan Q, Zhang J. Evaluation of 99mTc-CN5DG as a broad-spectrum SPECT probe for tumor imaging. Transl Oncol. 2021;14(1):100966.

Go To Transl Oncol

About Priti