As a veterinary oncologist I know that it is of utmost importance that prior to deciding on the appropriate cancer treatment for a patient that this patient has to be staged and the cancer graded. Grading a cancer means that a sample of the tumor is examined by a pathologist who decides what type of tumor it is and how aggressive it is (i.e., What are the chances this tumor is going to metastasize?). Staging a cancer means that we are trying to determine where the tumor is - Is it only affecting one area of the body? Has it already metastasized? And if so where has it gone? Does the patient have other health issues that will influence how we treat it or what medications we can use?

When we are staging we used multiple different types of imaging. The sensitivity of these imaging modalities varies widely. As we discussed during our lecture on "Imaging and Cancer," what imaging type we choose depends on a multitude of factors including availability, sensitivity to cancer detection, cost and the expertise of the veterinarian doing the interpretation. The least sensitive (but not necessarily the worse choice of imaging) is radiographs. The most sensitive (but not always the best choice of imaging) is something called positron emission tomography (PET) computed tomography (CT).

PET-CT exploits the combination of function with anatomy. We get the very specific localization of a disease process, like what is seen with nuclear medicine, with the very high spatial resolution of CT. As with nuclear medicine we will inject a patient with a radioisotope that has been tagged with a metabolic analogue of some kind. This radioisotope will decay via something called "positron emission." When this happens two high-energy photons are emitted at 180 degrees to each.

These photons are captured by a ring of detectors around the patient. The location and time it takes for a photon to get to a detector allows us to specifically localize it. In order to be able to interpret potential lesions that are identified, we fuse this portion of the study with a full body CT, which overcomes the inherent poor spatial resolution of nuclear medicine.

The most common radioisotope that is used in both human and veterinary medicine is something called Flourine18-flourodeoxyglucose (F-18FDG). F-18FDG is a glucose (that is, sugar) analogue that is taken up by metabolically active cells. This includes lots of normal tissues (salivary glands, intestines, brain) and is also highly sensitive to MOST cancers (some prostatic cancers and neuroendocrine tumors being the exception). One of the fascinating things about F-18FDG PET-CT is the biology behind why it works.

It seems intuitive that cancerous cells would use more glucose than their normal counterpart. But the actual biology behind it is more complex that what you would think. The discovery that cancer cells use more glucose than their normal counterparts was discovered back in the 1920s by a German biologist called Otto Warburg, and is now called "The Warburg Effect." Warburg discovered that cancer cells, even in a well oxygenated environments, will produce lactate, something normal cells do only under anaerobic (low oxygen) conditions. He termed this aerobic glycolysis. Glycolysis is not an efficient way to produce energy for the cells, which they measure in ATP. Therefore, in order to make more energy, cancer cells need more glucose.

From an evolutionary perspective this makes no sense. Why would a cancer cell put itself at a disadvantage of relying heavily on glucose? It turns out it's not about the glucose and the ATP, instead it's about the lactate. Lactate helps to support the uncontrolled proliferation of tumor cells by providing energy and building blocks for amino acids, lipids and nucleotides. In addition they protect tumor cells and provide a survival advantage over normal cells by creating an acidic microenvironment and scavenging reactive oxygen species.

In human medicine PET-CT is used to stage, diagnose, evaluate response and monitor patients, as well as to help define margins of a tumor. In veterinary medicine PET-CT is in its infancy and we are still working to determine how best to use it. The use of PET-CT in human medicine has grown by a thousand fold since its introduction for commercial use in the late 1990s.

At Colorado State University Veterinary Teaching hospital we have the only veterinary dedicated PET-CT in North America that is available for small animal clinical cases. To date we have acquired over 300 PET-CTs for clinical cases and well as innumerable cases for research purposes. In addition to staging for cancer with F-18 FDG we have used this radioisotope for diagnosing musculoskeletal problems, and fever of unknown origin. We have also used other radioisotopes such as sodium fluoride for diagnoses of boney metastases, and Copper 64 for identification of hypoxic regions in tumors. There has been research into thymidine, which reflects DNA synthesis via thymidine kinase. Thymidine kinase is an enzyme that is 4–3 times more active in malignant cells than normal.

There are a lot of downsides to the use of PET-CT, including the expense, the lack of veterinary facilities, the low specificity and the decreased spatial resolution. Having said that, in the right situation with an experienced team, PET-CT can provide valuable information in our veterinary cancer patients.