Imaging: Avastin + copper combine

22 Oct 2008

Bevacizumab PET/CT imaging found better than current gold standard

Scientists have developed a new imaging agent that can be used in scanning for tumours, which gives a much clearer and more precise image than existing methods. The discovery has the potential to revolutionise pre-clinical cancer research and clinical diagnostic practice, and it makes use of 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 US Food and Drug Administration (FDA) for some clinical trials.

Dr Zheng Jim Wang told the 20th EORTC-NCI-AACR* Symposium on Molecular Targets and Cancer Therapeutics in Geneva today that he and his colleagues had attached bevacizumab to a molecule called DOTA (a cyclic compound) and tagged it with a radioactive tracer, Copper-64 (Cu-64).

Bevacizumab is an antibody that targets vascular endothelial growth factor (VEGF), a signalling protein released by tumour cells and which plays an important role in angiogenesis (the process by which a growing tumour creates its own blood supply). Currently, bevacizumab 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 tumours, and that it enabled clear and well-defined images to be detected during scanning.

When compared with images of the same tumours 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.

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

“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.

“VEGF-related angiogenesis is almost a universal phenomenon for most types of solid tumours. We are testing this probe in different cancers (lung, pancreatic, ovarian, prostate, breast, and colon cancer) and bone metastasis models to verify our assumption. Once it’s been verified and validated, we are planning to test it in clinical trials.”

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.

* EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].