October 23, 2008 - A new imaging agent may detect early tumors in animal models better than 18FDG, according to research presented at the 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva, Switzerland.
The agent includes compounds that have already been approved for treating patients: the anti-cancer drug bevacizumab (Avastin) and Copper-64, a radioactive copper nuclide, which is approved by the FDA for some clinical trials.
Zheng Jim Wang, M.D., who spoke at the conference, said that he and his colleagues had attached bevacizumab to a molecule called DOTA and tagged it with a radioactive tracer, Copper-64 (64Cu). Bevacizumab is an antibody that targets vascular endothelial growth factor (VEGF), a signaling protein released by tumor cells, playing an important role in angiogenesis. Currently, bevacizumab is being used to treat patients with advanced colorectal cancer and is being tested in several other metastatic cancers.
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 tumours in the same animals taken the day before, using the current gold standard imaging probe for tumours (18-Fluoro-Deoxy-Glucose (18FDG)), they found that not only were the 64Cu-bevacizumab images better, but also that they could detect tumours in earlier stages and at smaller sizes than with 18FDG. In addition, 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; "hot spots" occur where the compound has accumulated not just in tumours but also in key organs (such as the heart, brain, kidneys and bladder) which give false positive signals.
"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 18FDG, 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 18FDG, it could detect a broader range of tumor types than 18FDG,” said Dr. Wang, director of Molecular Imaging at MPI Research Inc. and an adjunct assistant professor at University of Texas Health Science Center at San Antonio, TX.
He went on to point out that 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.
As VEGF-related angiogenesis is almost a universal phenomenon for most types of solid tumors, the researchers are testing this probe in different cancers - lung, pancreatic, ovarian, prostate, breast and colon cancer - as well as in bone metastasis models.
Once researchers have obtained the necessary confirmation of their results in further studies and clinical trials, imaging with 64Cu-bevacizumab could be used in both pre-clinical and clinical work.
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