FDG-PET/CT and the Evaluation of Breast Cancer

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Chapter 11 FDG-PET/CT and the Evaluation of Breast Cancer

Positron emission tomography (PET) scanning has gained widespread acceptance for the diagnosis, staging, and management of a variety of malignancies, including breast cancer. This has heralded an exciting new era of molecular imaging research, of which the use of 2-deoxy-2-(18F)fluoro-D-glucose (fluorodeoxyglucose, or FDG) as the primary PET tracer is only the beginning. The fundamental strength of PET over conventional imaging is the ability to convey functional information that even the most exquisitely detailed anatomic image cannot provide. The standard PET radiotracer in current clinical use, FDG is a glucose analog that is taken up by cells in proportion to their rate of glucose metabolism. The increased glycolytic rate and glucose avidity of malignant cells in comparison to normal tissue is the basis of the ability of FDG-PET imaging to accurately differentiate cancer from benign tissue regardless of morphology (Gambhir, 2002). The level or intensity of FDG uptake on PET is semi-quantified and reported as the standardized uptake value (SUV).

PET/CT Scanning Principles

The radiotracers employed in PET imaging, such as 18FDG, always emit pairs of photons that are 180 degrees apart as they decay. This is the key difference from the conventional radiotracers used in nuclear medicine, which only emit single photons in any direction at each decay event. Accordingly, PET scanners are designed as a ring of multiple pairs of photon detectors arranged 180 degrees apart with the patient lying in the middle of this ring. These pairs of photon detectors, which are made of either bismuth germanium oxide (BGO), gadolinium orthosilicate (GSO), lutetium orthosilicate (LSO) crystals, or lutetium yttrium orthosilicate (LYSO) (Box 11-1) are electronically linked such that they accept only pairs of photons that arrive at both detectors at exactly the same time point and reject scattered photons that arrive at incongruent time points (Fig. 11-1). This design allows for superior photon sensitivity and spatial resolution compared to conventional nuclear medicine scanners, which rely on the use of lead-based collimators that act as filters to reduce scattered photons that hit the camera face at tangential angles.

PET/CT scanners are integrated units with the individual PET and computed tomography (CT) components nearly identical to their stand-alone counterparts. Integrated PET/CT has the added advantage of using the CT data for attenuation correction and anatomic localization; additionally, more sophisticated PET/CT fusion software can be utilized for interpretation. CT-based attenuation correction, however, may introduce artifacts on PET when imaging high-density materials, such as bowel contrast and metallic prostheses. By comparison, stand-alone PET units do not utilize CT-based attenuation correction, but rely on a transmission scan generated by a built-in germanium-68 rod source within the scanner. The field of view of a modern PET/CT scanner is approximately 16 to 18 cm wide (see Box 11-1). The bed is advanced into the scanner in 6 to 7 increments so the patient can be scanned from the base of the skull to the midthigh. An additional 6 to 7 increments are required for scanning the extremities. Typically, each increment, termed a bed position, requires 3 to 7 minutes of acquisition time before moving on to the next section of the body. In contrast to conventional cross-sectional imaging, scanning starts at the pelvis and moves cranially to minimize the amount of urine accumulation in the bladder (Box 11-2).

FDG is the primary radiotracer in clinical use for oncologic PET and PET/CT scanning, including breast cancer screening. Once injected, FDG is transported into cells via the GLUT transport system and is quickly phosphorylated by hexokinase II. After phosphorylation, it is trapped within the cell, where it decays, with a physical half-life of 110 minutes. Typically, imaging commences 45 to 90 minutes after injection of tracer to allow adequate time for tumor accumulation and background washout from renal clearance. The average intensity of FDG uptake in malignant tissue is greater than in normal structures. However, physiologic tracer uptake of moderate intensity is typically seen in the liver, bowel, mediastinal blood pool, myocardium, and lymphoid tissue. Additionally, marked tracer uptake is seen in the kidneys, ureters, and bladder, where FDG is excreted.

Patient preparation before and after FDG PET/CT scanning is critical for high-quality scanning (see Box 11-2). High levels of either endogenous or injected insulin cause significant uptake of FDG in muscle and greatly decrease the sensitivity of the scan. For this reason, diabetic patients who have utilized regular insulin within 4 hours of FDG injection usually require rescheduling, as do patients who have eaten a meal within 8 hours. A less significant and somewhat controversial factor is that high levels of circulating glucose may potentially compete with FDG at tumor sites and, thereby, decrease sensitivity of the scan as well.

Accurate interpretation requires knowledge of the physiology of FDG as well as the limitations of PET scanning (Box 11-3). While greater SUV levels suggest a greater likelihood of malignancy, it is not reliable when used alone. Equally important is learning to differentiate focal from non-focal lesions through experience (there is no clinically used quantitative parameter for focality), with focal lesions more likely to be malignant than benign.

A multitude of common physiologic variants can also occur. These include marked fat activity, particularly in the head and neck (termed brown fat uptake), skeletal muscle uptake caused by physical activity after the injection of FDG, and increased areolar and ovarian activity, which is dependent on lactation and hormonal cycles. Even with abnormal FDG uptake beyond these physiologic variants, a host of benign processes may cause abnormal findings on PET scanning. These include infection and inflammation, certain benign or adenomatous lesions (including fibroadenomas occasionally), granulomatous disease, as well as other inflammatory conditions (Box 11-4).

Current efforts to improve PET resolution and sensitivity include the development of time-of-flight calculation techniques that account for the slight difference in time at which the pairs of photons arrive at the detectors to further localize the origin of positron decay within the patient (Surti et al., 2006

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