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Life Extension Magazine July 2012

Understanding the Functional Nature of Cancer: The Value of PET

By Kirk Stokel


Understanding the Functional Nature of Cancer: The Value of PET

The purpose of this article is to enlighten oncologists about superior imaging methodologies that can enable them to better recommend treatment options to their patients. It is very technical and most readers will find it challenging to comprehend. This article is meant for those stricken with cancer and their team of oncology experts. It is not for general audiences.

By Kirk Stokel

When cancer strikes, timely, accurate information is of the essence. Time, because the sooner an accurate diagnosis is made, the greater the chances of stopping the disease before it’s too late. Information, because cancer is a living thing that constantly changes both itself and its environment. It’s vital to know not only where a cancer has taken hold, but also what it is doing: how rapidly is it growing, is it spreading, is it destroying or invading adjacent tissue?

Physicians have been able to learn at least basic information about a cancer’s physical location since the invention of medical X-rays in the late 19th century.1-3 Today’s CT (computerized tomography) and MRI (magnetic resonance imaging) scanners provide exquisite details about the size, shape, and other anatomical features of an abnormal mass. Other techniques, however, are needed to determine if the mass is indeed a cancer, and if so, how aggressively it is spreading and invading.3

FDG (fluorodeoxyglucose) Molecule

Figure 1. FDG (fluorodeoxyglucose) Molecule. A radioactive label or tag called Fluorine 18 (F18) is produced in a cyclotron. It is added to molecules that cells utilize in their metabolism; in the case of FDG, the “parent” molecule is glucose. The F18 replaces an oxygen molecule resulting in fluorodeoxyglucose. The clinician usually orders this test as a 18F-FDG PET/CT scan.

Until recently, that functional information that relates to the metabolic activities of cells could be obtained only by invasive means such as biopsies or open surgeries. Much of that is changing now, with the advent of so-called functional imaging studies that can tell an experienced expert a great deal about an unknown mass. In the right hands, such information can allow an expert to distinguish between a malignant cancer and a benign mass, scar tissue, or focus of infection.

Positron Emission Tomography, or PET scanning, is rapidly emerging as one of the most useful forms of diagnostic imaging, especially with regard to diagnosing and managing cancer. 4-6 Like all imaging studies, however, PET scans are fraught with pitfalls for the uninitiated. As PET scanners appear in more and more hospitals, there’s a growing need for standardization of interpretation and reporting of results. Above all, there’s a need for experienced physicians to read the scans and provide useful information to the physicians who order them.

Sadly, that level of rigor and expertise is lacking in many hospitals around the country, according to Dr. Richard Black, Director of Nuclear Medicine and PET Imaging for Radisphere National Radiology Group based in Cleveland, Ohio. We caught up with Dr. Black recently to get a better understanding of PET scanning in general, and specifically to provide readers with a clear idea of the pitfalls, as well as the strengths, presented by this powerful new technology.

Let’s start with a basic synopsis of what a PET scanner does, and how it obtains functional or metabolic information about a tumor or other suspicious mass. Then we’ll see real patients from Dr. Black’s casebook on how PET scans are being used in caring for patients with malignancies. We’ll touch briefly on the practical limitations of PET scan technology. Then we’ll focus on Dr. Black’s breakthrough efforts to change the way PET scans are interpreted and reported. Dr. Black is leading the field in developing standardized, reproducible reports on literally tens of thousands of patients for his customers that are situated throughout the United States and abroad and thus allowing oncologists and other clinicians to derive maximum benefit from these imaging studies.

What Is PET Scanning?

PET Scanning

Figure 2. PET Scanning. If a patient undergoing a PET/CT scan has a malignant tumor that is avidly taking up glucose, it will also take up 18F-FDG (fluorodeoxyglucose). The positrons emitted by the FDG will collide with electrons within the patient. This results in the emission of gamma rays (photons), a form of energy, which is picked up by the PET scanner—a gamma ray detector. When the scanner detects a matching pair of gamma rays, a software program determines their point of origin and creates a three-dimensional image—the PET scan.

PET scanners produce functional information about a suspected tumor through the use of a technique that differs entirely from conventional radiology studies. The essence of the modus operandi—the method of operation—of PET is based in the world of quantum physics.

To conduct a PET scan, a technician injects a patient with a radioactive tracer material. The most commonly used material is fluorodeoxyglucose, or FDG. (See figure 1.) FDG consists of a molecule of glucose chemically linked to a radioisotope of fluorine called 18F. Like glucose, FDG is taken up into cells through a variety of specialized transporters and enzyme systems. The more metabolically active a cell is, the more glucose, and hence, FDG, it takes up.7 Cancer cells are highly metabolically active because of their rapid rate of reproduction; that means that they take up FDG much more avidly than surrounding normal tissue.8-10

The radioactive fluorine isotope in FDG is constantly emitting a stream of positrons, the antimatter equivalent of electrons. Each time a positron encounters an electron, the two particles annihilate each other in a matter-antimatter implosion, giving off a pair of photons (little packets of energy).11 The photons trigger a signal on detectors built into the PET scanner (See figure 2), and powerful computers assemble all of those signals into a coherent 3-dimensional image. Areas of the most intense glucose utilization, then, will “light up” as areas of high metabolic activity, which indicate the presence of cancer with a very high likelihood.7,9,11-13

Of course, there’s a trade-off for everything. While they produce vivid images of cells’ functional, metabolic activity, PET scans by themselves don’t produce a very precise anatomical picture. The solution is to combine the findings of a PET scan with those of a conventional imaging study (usually a CT scan) that can provide detailed anatomical information. With both PET and CT images “in register,” they can be readily superimposed to provide the diagnostician with both anatomical and metabolic information about the tissues and organs of interest. This is the PET/CT scan that is in use today.

What You Need to Know: Role of Functional PET Scans in Cancer Care
Role of Functional PET Scans in Cancer Care
  • Effective treatment of cancer requires rapid and accurate acquisition of information about tumor size, location, and rate of growth.
  • Diagnosing cancer also requires the ability to distinguish true malignancies from benign masses or sites of inflammation.
  • Most modern medical imaging techniques can provide only anatomic or structural information about a mass, and offer no functional information (how the tumor tissue differs from healthy tissue surrounding it.)
  • PET scans use principles of quantum physics to highlight areas of tissue that have abnormally high glucose requirements; such areas are very often cancers
  • PET scans are extremely useful in primary diagnosis of cancer and in following a patient’s response to treatment, but their interpretation is fraught with a variety of readily-made errors.
  • Dr. Richard Black is leading the field in his tireless activism for a standardized, quantifiable approach to interpreting PET scans in order to provide oncologists and their patients with full potential this technology has to offer.

How Are PET/CT Scans Used?

With their rich supply of functional data on cellular metabolism, PET scans have tremendous potential in oncology. Dr. Black points out that, “A PET scan report should tell a clinician what he or she really wants and needs to know to facilitate and optimize individual patient management. The report should not be a long, convoluted listing of findings without interpretation and explanation. Most importantly, a PET scan should be able to change and assist how a clinician manages a patient.”

According to Dr. Black, PET scans can correctly and successfully change patient management in an average of 30% of cases compared to conventional imaging techniques that include CT, MRI, plain film radiography etc. Other experts estimate that figure as high as 38%.14 These findings translate to a huge impact on outcomes, given the millions of cases of cancer in the US each year.15 FDG PET/CT scans are useful for differentiating benign from malignant lesions, evaluating tumor stage, monitoring the response to therapy and detecting tumor recurrence in a variety of malignancies.5

Here are a few case studies from Dr. Black’s files and the medical literature, indicating just how PET scans were used, and the impact they had on management.

Assigning a higher stage to a known cancer

Case #1: Assigning a higher stage to a known cancer.13 A 63-year-old man with a recent diagnosis of a primary colon cancer was evaluated by PET/CT scan following surgical removal of the tumor. At surgery, no spread to lymph nodes, and no tumor metastases were found. The PET/CT study, however, revealed metastases in the patient’s liver, resulting in a higher clinical stage. Because of this finding, the treatment options for this patient were dramatically changed.

Assigning a lower stage to a known cancer

Case #2: Assigning a lower stage to a known cancer.13 An 85-year-old man with a recent diagnosis of Merkel cell carcinoma, a rare and highly aggressive skin cancer, had undergone a CT scan that suggested three separate metastases in the liver. A PET/CT scan was done to confirm that metastatic spread, but instead it showed completely normal liver tissue. This patient’s disease was “down-staged,” and he was spared unnecessary chemotherapy.

Monitoring a patient’s favorable response to therapy

Case #3: Monitoring a patient’s favorable response to therapy.13,16 A 79-year-old woman with a history of lung cancer, treated with chemotherapy in April of 2009, underwent a PET/CT scan in July of that year. A CT scan still showed a nodule at the site of the original cancer, and was read as showing persistent disease. The PET scan, however, revealed a complete metabolic response to treatment, indicating in fact no residual tumor.

Monitoring a patient’s unfavorable response to therapy

Case #4: Monitoring a patient’s unfavorable response to therapy.13 A 72-year-old woman with lung cancer, treated in November of 2010, was given a CT scan in February 2011 to determine her response. Her tumor had not changed size, and the scan was therefore interpreted as showing stable disease with no progression. A PET/CT scan that same day was more informative, demonstrating that in fact her left lung was highly metabolically active, indicating progressive disease. This patient required additional treatment.

Cancer Cell
Cancer Cell

In each of these cases, PET/CT studies provided valuable information about the metabolic activity of tissue. Such information that could not be obtained from the anatomic data provided by CT alone (or, in Case 3, by direct examination during surgery). These cases provide persuasive evidence that PET/CT scans change patient management in a variety of important ways.

Let’s now examine some of the limitations of PET technology, and learn how Dr. Black is working to overcome these limitations to obtain the most useful information possible.