A new PET imaging agent

A new imaging agent, 64Cu-DOTA-bevacizumab, has been developed for scanning of tumor growth and functional imaging of angiogenesis in animal tumor models. The new agent gives a much clearer and more precise image than existing methods (18FDG). This discovery has the potential to revolutionise preclinical cancer research and possibly clinical practice of cancer diagnosis.

Tumor imaging
New drug discovery generally spans ten to 15 years. To develop novel drugs more quickly and cost-effectively, many new technologies have been used, including multi-modality imaging techniques. Positron emission tomography (PET) is a noninvasive imaging technique that provides a means to obtain information about drug behavior and functional efficacy during drug development.

PET is used extensively in both preclinical research and clinical practice of cancer diagnosis and therapy. In the past two decades, hundreds of articles have been published on cancer drug development in the field of therapeutic PET imaging of cancer patients and preclinical cancer research on tumor animal models. The articles focus mainly on the gold-standard imaging agent 18FDG (Fluoro-18-Deoxy-Glucose), which monitors the metabolic functional change of tumors. In recent years, tumor angiogenesis imaging has drawn a lot of attention to anti-angiogenic drug development.

Angiogenesis is a fundamental process in which a growing tumor creates its own blood supply by forming new blood vessels around tumor tissue. Bevacizumab is an antibody that targets vascular endothelial growth factor (VEGF), a signaling protein released by tumor cells, and plays an important role in angiogenesis. VEGF-related angiogenesis is a nearly universal phenomenon for most types of solid tumors. Currently, bevacizumab is being used to treat patients with advanced colorectal cancer and is being tested in several other metastatic cancers.

Based on our preliminary imaging results, the new imaging agent 64Cu-DOTA-bevacizumab is able to serve as the next generation of PET imaging agents in preclinical cancer drug research in the following directions:

Tumour growth
The new imaging agent could help researchers detect and observe the growth of tumors located at greater depth in the body and offers better sensitivity and diagnostic imaging contrast.

Estimate tumor size
According to our results, bevacizumab imaging offers clearer contours of the tumors than other probes. With appropriate image analysis and experiment design, it could help researchers estimate the size of tumors and further monitor the therapeutic effect of certain treatments.

Observe angiogenesis-related events
The release of VEGF is strongly related to angiogenesis. 64Cu-DOTA-bevacizumab can provide information about distribution and change of VEGF at different time points. Furthermore, this information can be used for evaluation of the functional effect of other anti-angiogenesis drugs. Also, it can tell the researcher which part of the tumor is actively undergoing angiogenesis at a specific time point. VEGF is related to hypoxia and inflammation as well. Therefore, this probe may be used to obtain indirect indication of hypoxia and inflammation.

Evaluate other anti-cancer drug candidates
It could offer information on the percentage of the total injection dose of bevacizumab accumulated in a tumor and in other organs as a contrast. The pharmacokinetics and distribution of bevacizumab in the tumor could be revealed by dynamic PET imaging. The same imaging strategy can be used to evaluate the pharmacokinetics and distribution of other anti-cancer drug candidates, such as antibody, aptamer, siRNA, hormone, peptide, and oligonucleatide.

64Cu-DOTA-bevacizumab can be used as a tumor diagnostic agent by PET imaging in preclinical research on animal models. The radiolabeled tracer as a new imaging agent is highly sensitive in pancreatic, breast, and lung cancer animal models, and possibly in other types of solid tumor animal models. The tumor-tissue contrast and in vivo bio-distribution are superior to the current clinical standard 18FDG imaging in tumor animal models.

For more information on this presentation, please visit www.mpiresearch.com.

Dr. Zheng “Jim” Wang has more than 12 years of experience in molecular imaging research and nuclear medicine. He was an assistant professor at the University of Texas Health Science Center at San Antonio and is currently the Director of Molecular Imaging at MPI Research. 

[CREDIT TEXT]
Zheng Wang1, 2, Ting-Tung Chang2, Mark Lane1, Jia-Hao Xiao1, Dale Mais1, Tina Rogers1
1 MPI Research, Mattawan, Michigan 49071, USA
2 University of Texas Health Science Center at San Antonio, Texas 78229, USA