Cancer drug Avastin bests gold-standard PET agent at detecting tumors

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Scientists have developed a new imaging agent, Avastin, that can be used in scanning for tumors, and which gives a much clearer and more precise image than existing methods, according to a study presented Wednesday at the 20th EORTC-NCI-AACR symposium on Molecular Targets and Cancer Therapeutics in Geneva, Switzerland.

Avastin was the first clinically available angiogenesis inhibitor in the United States for clinical trials.

Zheng Jim Wang, MD, and colleagues attached Avastin (bevacizumab from Genentech and Roche) to a molecule called DOTA and tagged it with a radioactive tracer, Copper-64 (64Cu). Avastin is an antibody that targets vascular endothelial growth factor (VEGF), a signaling protein released by tumor cells and which plays a role in angiogenesis. Currently, Avastin is being used to treat patients with advanced colorectal cancer and is being tested in several other metastatic cancers.

When the researchers injected the compound (64Cu-bevacizumab) into mice with breast, lung and pancreatic cancers and then used PET/CT imaging to scan the animals, they found that it successfully targeted the cancer cells, accumulating in high concentrations in the tumors, and that it enabled clear and well-defined images of the tumors to be detected during scanning.

When compared with images of the same tumors in the same animals taken the day before, using the current gold-standard imaging probe for tumors (18-FDG)), the researchers found that not only were the 64Cu-bevacizumab images better, but also that they could detect tumors in earlier stages and at smaller sizes than with 18-FDG. Also, the 64Cu-bevacizumab images had none of the conventional ‘hot spots’ that tend to appear in 18FDG images and which affect the accuracy of the imaging.

“Our collaborative research reveals and verifies a new imaging agent for the next generation of tumor detection imaging probes. 64Cu-bevacizumab is highly sensitive in pancreatic, breast and lung cancer models, detecting tumors earlier than 18-FDG, with much better contrast between the tumor and the surrounding tissue and with fewer non-tumor-related hot spots. Because it uses different biological mechanisms compared with 18-FDG, it could detect a broader range of tumor types than 18-FDG,” said Wang, director of molecular imaging at MPI Research in Mattawan, Mich., and an assistant professor at University of Texas Health Science Center at San Antonio:

"Since bevacizumab has been approved by the FDA for treating patients and Copper-64 for clinical trials, the conjugated compound has a much higher chance of being applied to clinical use faster than other, newly developed bimolecular compounds,” Wang added. “VEGF-related angiogenesis is almost a universal phenomenon for most types of solid tumors. We are testing this probe in different cancers and bone metastasis models to verify our assumption. Once it's been verified and validated, we are planning to test it in clinical trials."

Wang and colleagues are the first to show that it is possible to use Avastin as a diagnostic imaging agent to detect early tumors in animal models and that it is better than the gold standard 18-FDG.

However, while Wang and colleagues started the project, some scientists and doctors in the cancer field did not believe their idea could work because VEGF is diffusible and breaks down very quickly. “They highly doubted the research goal and some of them refused to believe the first imaging result, which was thought too good to be true," he said.

Wang said that it is possible to use Avastin as a diagnostic imaging agent to detect early tumors in animal models and that it is better than the gold standard 18-FDG. However, he said that when he and his colleagues first started the project, some scientists and doctors in the cancer field did not believe their idea could work because VEGF is diffusible and breaks down very quickly. "They highly doubted the research goal and some of them refused to believe the first imaging result, which was thought too good to be true," he said.

The researchers persisted, and last year, another research group in the Netherlands published similar results in an ovarian tumor model. "Eventually we found out that while some types of VEGF are diffusible, other types of VEGF are located at the tumor cell surface and very near the extra cellular matrix. That is why the radiolabeled bevacizumab targets VEGF on the angiogenesis site around the tumor and demonstrates excellent imaging of the tumor. Since we are targeting early stage of angiogenesis we are able to see the tumor when it is still very small or in other words, in a very early stage."

Once researchers have obtained the necessary confirmation of their results in further studies and clinical trials, they said that imaging with 64Cu-bevacizumab could be used in both pre-clinical and clinical work.