PET/CT Cancer Imaging: Cancers Eat a lot of Sugar

About the Lecture

There are many different ways to detect and diagnose cancer. PET imaging is one way to accomplish this. For PET imaging, patients are injected with a small amount of a radioactively marked sugar which, once in the body, reach those organs and tissues that consume a lot of sugar. Tumors consume up to 30 times more sugar then normal tissue. Since the injected sugar is radioactive we can detect its location in the body with a scanner, the PET scanner. The scan then provides us with the following information.

Is it cancer? What organs are involved? Has the cancer spread? Did the treatment work?

These are questions that the oncologist and the patient and family wonder and hope for reliable and valid answers. One decade ago work began that resulted in what is now called the clinical PET/CT and it is the most exciting and novel imaging tool in oncology today. This tool has dramatically changed how these important questions are addressed. At UCLA over 7000 patients have been studied with the new technology and there is a diagnostic advantage in about 15% of patients with cancer over the previous PET scan alone. As a result more than 2000 PET/CT scanners have been installed worldwide. This presentation helps patients and their family members to understand how imaging techniques are an integral part of comprehensive cancer care. PET/CT imaging plays a vital role in determining stage, and effectiveness of treatments and there is clinical evidence that it is superior to PET or CT alone. Several types of cancer will be used to illustrate how PET/CT is used in diseases such as breast, lung cancer and lymphoma and sarcoma.

Speaker

Johannes Czernin, MD, Professor, Vice Chairman Molecular and Medical Pharmacology, Director of Nuclear Medicine at UCLA and Chief of the Ahmanson Biological Imaging Division at UCLA, received his degree from the University of Vienna, Austria Medical School. He began his work as a postdoctoral scholar at UCLA in 1989. Initially focusing on PET imaging of the heart, he turned his interest to cancer imaging with FDG-PET in 1997. He has established a large clinical research program addressing the usefulness of PET imaging for managing cancer patients.

Lecture Summary

This is a summary of a lecture presented on May 14, 2013.

In 1971, President Nixon signed the National Cancer Act, a United States federal law aimed at strengthening the National Cancer Institute to more effectively carry out the national effort against cancer. Along with Dr. Alva Letton, leader of the American Cancer Society, the President of the United Stated declared “War on Cancer.” When President Nixon left office, cancer was still a major threat to life. 42 years later, we are still at war with cancer.

Costs and Cancer

Cancer care costs exceed $100 billion; overall health care costs are approximately $2 trillion per year. The United States spends approximately 15.2% of the GDP on health care, and this is expected to rise. The percentage of private expenditures toward health care has been decreasing, while the percentage of public expenditures has continued to rise. The incidence of the most common cancers has been rising since 1975; however, the mortality rates have been decreasing. When Medicare cost data for cancer were evaluated, the non-imaging cancer expenditures accounted for approximately 95.4% of the expenses while imaging only accounts for 4.6% of total costs. When further divided, 1% of costs are accounted for by PET imaging and 3.6% are attributed to other imaging techniques. Medicare reimburses PET/CT at $1250 per scan.

Imaging Tests in Cancer

There are three key imaging modalities: MRI, CT, and PET.

Magnetic Resonance Imaging (MRI) creates a powerful magnetic field through which images are created by turning this field on and off. It is best for imaging brain, bone marrow, soft tissues such as muscles, liver, and pancreas, and is used for a variety of cancers. It is a precise imaging technique and is exquisitely accurate. The whole body can be done in approximately 25 minutes. An MRI scanner is very powerful. Because of the intense magnetic field, it is not safe to have any metals in the room with an MRI scanner. Metallic prostheses are usually safe. MRI scanners are shaped like tubes or a tunnel; because of this, some patients experience claustrophobia and may need an anti-anxiety medication while having MRI scans. There is also noise associated with these scans, which can sometimes be bothersome to patients, but earplugs will make a difference.

Computer [Assisted] Tomography (CAT or CT) can scan the whole body in 10 seconds. It uses x-rays to produce images of the body. Radiation doses are higher than from one x-ray as many x-rays are taken to form a complete picture. CT scans are good at showing anatomical structures.

There has been much discussion about the exposure that an individual receives from these types of scans. Many patients become worried about this because they may not have a perspective that helps them see the risks and benefits in an understandable way. Overall, CT scans are valuable and provide relatively low doses of radiation without significant consequences. A Gray (Gy) is a method of quantifying exposure/absorption of radiation. In general, most people are exposed to 2.4 mGy (milligray) per year from the background radiation in the environment. A CT scan can be 10-20 mGy, which is 10-20 one thousandth of a Gy. Radiation therapy on the other hand, uses 45-60 Gy, which is thousands of times higher than the radiation used in one CT scan. There has been ongoing research into the question of whether CT imaging is dangerous. There have been multiple studies published recently, and the conclusion is, “Predictions of hypothetical cancer incidence and deaths in patient populations exposed to such low doses [in imaging] are highly speculative and should be discouraged.” However, despite the scientific evidence, information abounds on the Internet that may lead people to be fearful of imaging. It is not uncommon to hear people use the phrase it is a “one in a million chance.” To provide another perspective, the table below provides a listing of some activities that increase the annual probability of death by “one in a million.” This was published in Imaging Physics in 2011.

Amount Activity Cause of Death 1.2 mrem (1/100 Sv) Chest x-ray Cancer 3 Days Living in the US Homicide 1 Day Live in Boston Air pollution 1 Cigarette Cancer 0.5 L Wine Cirrhosis 10 spoons Peanut butter Liver cancer 1 gallon Miami Drinking water Chloroform 6 min Canoeing Drowning 50 Miles Automobile Accident 5 Miles Motorcycle Accident 1 week Visit to Denver Cosmic rays 150 years Living 20 miles from a reactor Radiation

Positron emission tomography (PET) is a scanning technique that tracks the uptake of sugar throughout healthy and abnormal tissues of the entire body. The PET scan is a method that enables us to see function rather than anatomy. PET scans identify areas in the body that are absorbing sugar. As a result, the brain and heart show up on PET scans because these are highly active tissues in the body that absorb sugar as fuel. To determine which tissues are absorbing high quantities of sugar, prior to your scan your medical health practitioner needs to inject into a vein a small amount of sugar that has a small amount of radioactivity attached to it. The radioactive tracer is called FDG, which stands for 2-[f-18] fluoro-2-deoxy-d-glucose. After the sugar has traveled through your body and been absorbed, PET identifies those areas that have high uptake of sugar, other than those already known to be high utilizers of sugar, e.g., the brain; these areas can indicate the presence of cancer.

The high utilization of sugar in cancer is based on an important discovery made in 1921 by Otto Warburg when he studied the metabolism of cancerous cells. He found that the respiration of oxygen in normal body cells is replaced in cancerous cells by a fermentation of sugar. Normal body cells meet their energy needs by respiration of oxygen, whereas cancer cells meet their energy needs in large part by fermentation. From the standpoint of the physics and chemistry of life, this difference between normal and cancer cells is hugely significant. Oxygen gas is the source of energy in plants and animals; in cancer cells that process is replaced by an energy yielding reaction of the lowest living forms, namely the fermentation of glucose. In the 1970s the Brookhaven group synthesized 18F-FDG the radioisotope that can carry sugar. In 1975 the first PET scanner was developed by Michael E. Phelps, PhD, Chair of the Department of Molecular and Medical Pharmacology at the David Geffen School of Medicine at UCLA. The PET scanner allowed us to carry out the first clinical studies in neurology, cardiology, and oncology by following the uptake of the radioactive isotope used in PET imaging to determine how the body’s organs use sugar. The research continued to progress, scanners became better and ultimately, imaging studies were conducted. PET scans are incredibly useful because cancer cells, by nature, are rapidly dividing. After 90 hours of cell division, one cancer cell can become 32,768 thousand cells. A one centimeter tumor contains 10 billion cancer cells. This rapid cell division requires a large amount of fuel, and that fuel is the sugar in our body. However, don’t suddenly run out and throw out all your foods containing sugar or stop eating fruit. Keep reading because I will be specifically addressing this topic and your concern further along!

During the 1980s and 1990s the quality of the PET scans improved and scans became more useful and specific. FDG, the sugar-based isotope, decays quickly therefore linear accelerators are needed on site to produce FDG. Since the 1980s there has been a huge increase in the number of centers that use PET devices.

One of the great advances of imaging technology was the ability to integrate CT and PET scanners into one machine and to superimpose images one upon the other. CT scans show anatomical structures but are not as effective at determining attributes of the structures. The PET scan indicates whether there is strong uptake of sugar and is, thus, useful in diagnosing the presence of most cancers. The PET/CT scanner produces an image of the anatomy fused with the functional images of the use of sugar by cells.

PET/CT imaging helps to determine where a primary tumor is located. For example, it can help to determine whether cancer can be removed by surgery or whether the lesions are outside the scope of a surgical intervention. It is also useful in determining if cancer has recurred, making PET/CT imaging highly significant in making treatment decisions. It has become even more important as a tool in evaluating whether a treatment protocol is working. As a result, patients can stop ineffective treatments more quickly and move to something more effective for their cancer. This is a critical decision for patients because it helps avoid unnecessary exposure to toxicities of ineffective treatments, it saves money by preventing unnecessary, often highly expensive, treatments, and most of all, allows your oncologist to switch you to a more effective treatment in a timely manner.

The National Oncology PET registry (NOPR) is collaboration between Medicare and a group of researchers. This collaborative effort helped to evaluate impact of PET/CT on the management of cancer patients. Multiple studies have been published between 2007 through 2011 showing that cancer staging and restaging has been greatly affected by PET in most forms of cancer. Because of this research, PET/CT is now covered by insurances for most forms of cancer. Primary prostate cancer is one of the few not covered but we are now allowed to monitor with PET therapeutic responses of prostate cancer that have spread. There are some exceptions for breast and melanoma. Several other studies have shown that the inclusion of PET in the management of cancer patients can result in improved survival. The first set of images show a normal CT scan, a normal PET scan and a normal PET/CT combined. The second set of images, an abnormal CT scan, an abnormal PET and the fused PET/CT, shows that the abnormal areas of anatomy on the lung and adrenal gland are functioning abnormally because of the high uptake of the sugar.

Preparation for PET/CT Scan

It is important that you prepare appropriately for a PET/CT scan. Patients often receive intravenous contrast injection for the CT portion of the PET/CT scan; therefore, prior to getting a PET/CT scan, blood creatinine levels must be monitored via a blood test prior to the procedure to assess the function of your kidneys.

Patients are asked to fast for 4-6 hours prior to the scan but are allowed to drink fluids. You should not exercise on the day of or the day before a PET scan because muscles use a lot of sugar and exercising could cause a more diffuse uptake of the radioactive tracer into the muscles instead of the potential tumor sites, creating images that are more difficult to interpret. Regular medications should be taken on scan day including medications for controlling diabetes. It is important to stay warm, during the period that the tracer is in the body, because there is something called “brown fat” that is characteristic in infants, young adults and some older adults. When cold, this “brown fat” will take up sugar, leading to a scan that is difficult to read. Do not worry if the scanner room is cool. Blankets are usually given, but by the time you are in the scanner, the FDG has already distributed throughout the body. Wear warm clothing when you come to the clinic for imaging to keep your body warm and comfortable. This will also prevent the brown fat from using a lot of sugar.

The Actual Scan Procedure

Patients who have never had a PET/CT scan wonder what the steps are. Overall, it should take about 30 minutes for the actual scan. But since the FDG is injected 1 hour before we start imaging you should reserve a total of close to 2 hours for your visit. Sometimes, we will run a little late because another patient needed more time for imaging.

The basic steps from arrival at the clinic are

You will be greeted and basic information will be exchanged

You will be moved into an injection room

You will be injected with FDG

You might receive oral contrast, which we use to get a better CT image of your gut (you will probably not like the taste of the oral contrast agent but you will easily tolerate it).

You will be positioned in a comfortable recliner for about one hour and should be kept warm. If you are not warm, ask for blankets.

You are taken to the scanner (next door)

You are placed on the scanner bed (the room is fairly cold)

The contrast material for the CT portion will be injected

The CT images are taken (less than one minute)

The PET images are taken (around 25 minutes)

The report will be available within 24 hours although most of the time it will be available for your treating physician within a few hours.

Concerns and Questions after the Scan

There are very few side effects from these scans. A PET scan may create pain at the site of the IV injection, and very rarely, an infection. About 5% of patients have claustrophobia in the scanner. For patients who are anxious about the scans, benzodiazepines such as valium are very effective anti-anxiety medications that can be taken beforehand. Discuss this with your doctor before the scan. If you do take valium you will need to be driven to and from the clinic by a relative or a friend. The radiation exposure from the scan is low and is not dangerous if the scans are used as currently indicated. For the CT component, the IV contrast can cause allergic responses, and patients with kidney problems may need to be careful about the contrast. Oral contrast can cause abdominal discomfort in some patients. After the scan you are not radioactive, and there is no danger to you or to others around you. You can be in contact with children, pregnant women or anyone else. If you drink fluids it will wash out the radioactive sugar tracer more quickly. You are allowed to eat whatever you want after the scan is over.

The Internet, CAM and Myths about Sugar and Cancer

It must be noted that while Warburg’s finding about the use of sugar for cancers was an important scientific finding. However, postings on the Internet have created misleading and inaccurate conclusions about the relationship between cancer and sugar intake. Warburg’s findings did not state that eating sugar leads to cancer. It is important to understand more about this in order to avoid “diets and cures” that are misrepresented on the Internet.

The human body relies on glucose. Certain organs, especially the brain and the heart, two of our most vital and hard-working body parts, consume extremely high amounts of glucose because they require high amounts of energy. For example, if the body does not have enough glucose, it converts other things, such as fatty acids and proteins into glucose. It is true, however, that in comparison to most cells, cancer does have a sweet tooth. Cancer cells consume about 20-30 times more sugar than normal cells because cancers are rapidly dividing cells; in order to divide rapidly, they need energy. Glucose (sugar) is a rapid energy source, so while cancer cells do eat proteins and fatty acids as well, they rely on glucose. Though “technically correct,” the concept that sugar feeds cancer is also misleading because sugar feeds every cell in our bodies. Even if you could cut every bit of sugar out of your diet, your body would make sugar from other sources. All cells—healthy and cancerous—need sugar to grow. It helps to remember that there is nothing particular about sugar that “feeds” cancer cells any more than sugar feeds all of the cells in our bodies. The body makes its own sugar. It is impossible to starve a cancer by creating a diet that is absent of sugar.

The Internet is full of articles, misperceptions, and claims that focus on the relationship between cancer cells and sugar. Unfortunately, anyone can post anything on the Internet, and there is no filter for the facts. Just because something is in print or on the Internet does not mean that the information is accurate or meaningful. It is important to turn to real science to understand what we know. An excellent source for cancer information is the NCI website, www.nci.gov. Many patients want to understand what they can do to help themselves in addition to traditional cancer treatments. It is important to understand that there are no miraculous cures for cancer to be found on the Internet—if there were any miracle cures the scientific community would be using them. Conventional medicine still has the best treatments available for the reduction of cancer growth. However, complementary and alternative medicine practices (CAM) can be important and supportive adjunctive modalities. It is important to use the same scrutiny that one demands of traditional treatments to examine the value of these other approaches. You carefully should read the literature being published. There are important available data on the Internet related to diet, acupuncture, and massage in relation to cancer prevention, symptom management, and well-being; there are, however, equal amounts of inappropriate and misleading data and suggestions! There are important facts that every patient should investigate, e.g., acupuncture appears to be beneficial in reducing treatment-related symptoms; shark cartilage is very good for sharks but does not appear to improve cancer outcomes in humans; massage may benefit patients with cancer related fatigue; Laetrile (laevo-mandelonitrile-beta-glucuronoside) is ineffective against cancer at best and may be potentially harmful; and garlic may not lower bad cholesterol as originally thought nor does it appear to have an impact on colo-rectal cancer. These are just some of the medical miracles, or myths, which you can find on the Internet. Some claims are, however, significant. Low-fat diets may have a role in lowering the likelihood of cancer recurrence for women with breast cancer, but the mechanisms are not yet clear. Losing weight by cutting calories can reduce the risk of many health conditions such as cancer, diabetes, heart disease, and stroke. It is important to talk to reliable health care providers about the many messages out there to determine the best individualized plan for you. Be careful with the information found on websites.

Most important, chemotherapy frequently causes lack of appetite and end-stage cancer patients lose weight. Adequate intake of calories, vitamins, and other nutrients are important and may be important factors in quality of life. Consultation with a highly qualified and educated health specialist in nutrition may be helpful to your overall wellness.

UCLA PET IMAGING

The Ahmanson Translational Imaging Division at UCLA integrates biology, chemistry, radiochemistry, physics, and imaging to develop diagnostics and therapeutics to improve the outcome of cancer patients. It is in this environment that the PET imaging techniques were developed and continue to be developed to facilitate better care for patients.

At UCLA there are two locations that PET/CT’s are done. One is located on the main campus in Westwood and the other one in Santa Monica. When making an appointment, let the scheduling person know where you want the test done as well as any known allergies, medications, diabetes, and blood test for creatinine. These scans are not advised during the first trimester of pregnancy.

Information can be found at http://pet.ucla.edu/ and the locations are listed below:

UCLA Westwood Nuclear Medicine and PET/CT

Peter Morton Medical Building

200 Medical Plaza, Suite B114

Los Angeles, CA 90024

Phone: 310-794-1005

Fax: 310-267-0227

Hours: 7:30am-5pm

UCLA Santa Monica PET/CT

1245 16th St. Suite 105

Santa Monica, CA 90404

Appointments: 310-319-4970

Fax: 310-319-4980

Hours: M-F, 7am-4pm

Conclusions