The Role of Clinical Studies for Pets with Naturally Occurring Tumors in Translational Cancer Research: Workshop Summary by Sharyl J. Nass

Author:Sharyl J. Nass
Language: eng
Format: epub
Publisher: The National Academies Press
Published: 2015-12-26T00:00:00+00:00

IMAGING TECHNOLOGY IN CLINICAL TRIALS FOR PET PATIENTS

Challenges and Opportunities in Using PET Imaging in Clinical Trials

Peter Choyke from NCI discussed positron emission tomography (PET) imaging in clinical trials for pet patients. In general, radioactive tracers used in PET imaging depend on a high target-to-background ratio (TBR), he said, adding that data from mouse studies generally provide overestimates of the tracer target affinity and underestimates of background. Imaging background is related to PK, and the PK of rodents is very different from that of larger mammals. Thus, larger mammals will provide a more realistic estimate of TBR in humans, he said. Some of the challenges in pet patients relate to the co-administration of general anesthesia with the radioactive tracer during scanning and the handling of radioactive waste during and after a scan. There are also technical considerations that arise in imaging trials in pets. These include the fact that the equipment is typically dual use—PET scanners are generally not dedicated to canine use—which makes it necessary to separate the scheduling of pet and human patients, usually by 1 or 2 hours. There are also requirements for specialized staffing, including PET technologists, veterinary staff, and imaging specialists. There is also the concern about radiation safety; pet patients eliminate unpredictably, and this waste is radioactive. When human patients get PET scans, the radioactive waste (which generally has a short half-life) enters the municipal sewer system where it is very diluted and thus does not pose a safety a concern. For pet patients, temporary housing is usually provided until most of the tracer is cleared from the animal’s body. However, he added that while most tracers are cleared very quickly, others can take days to leave the animal’s system.

Choyke next discussed types of PET imaging agents. Receptor-specific imaging agents are highly targeted but can be slightly more difficult to work with in canine patients, he said, because the receptors in dogs are not identical to those in humans. Thus, the radiochemistry for the human version does not work for the canine version, and the agent must be reworked to accommodate the differences between the canine and the human receptor. For these reasons, other tracers are more commonly used in imaging of pet patients.

Choyke described several examples of studies with commonly used PET imaging agents. By using 18FDG (flourodeoxyglucose), which is a marker of metabolism, he said it was possible to examine tumor regression in a pet patient with B cell NHL after treatment with conventional chemotherapy. This is an excellent example of PET imaging for veterinary use, he emphasized. Another useful agent for both human and pet clinical trials is fluorothymidine (18FLT), which is a marker of cellular proliferative activity. 18FLT can be very specific for cancer and can allow differentiation between tumor and non-tumor tissue, he added.

Choyke also said that the PET imaging agent 18F-tetrafluoroborate (18F-TFB) has mainly been used in animals, but it may also be useful in human clinical trials. 18F-TFB images the sodium/iodide symporter (NIS) protein, so the agent

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