Background
Breast positron emission tomography (PET) is an organ-specific high-resolution technology that is used to visualize the metabolism of the breast. PET scanning is a nuclear medicine technique that images the flow of molecules in the body. This is made possible by attaching a radionuclide to a molecule that enters into metabolic pathways; the photons emitted when the radionuclide decays are then imaged. While anatomic imaging allows visualization of body structures, PET molecular imaging allows visualization of molecular flow and metabolic processes within the body. [1, 2, 3, 4, 5]
The primary benefit of PET imaging is that diseases such as cancer often first manifest as disordered metabolism before anatomic changes can be seen. [6, 7] In addition, dense breast tissue or scarring may cause anatomic techniques (mammography, MRI, ultrasonography) to be indeterminate. In such cases, knowing whether an anatomic structure is glucose hypermetabolic can be critical in the determination of proper medical management. [8, 9]
Breast PET typically utilizes the radiotracer F-18 fluorodeoxyglucose (F-18 FDG) to image glucose metabolism [10, 11] ; however, other radiotracers are under development. L-methyl-[11C]-methionine ([11C]C-MET) is one of the first radiolabeled amino acids used to assess amino acid metabolism in PET imaging. Uptake of [18F]F-FACBC ([18F]-fluciclovine) has been shown to be higher in breast cancer lesions than in benign lesions and healthy breast tissue, with a higher uptake in patients with a higher tumor grade. In some studies, [11C]C-labeled tyrosine (L-[1-11C]C-tyrosine), has been shown to be more accurate than F-18 FDG in differentiating malignant lesions from benign lesions, and [18F]-(2S, 4R)4-fluoroglutamine ([18F]F-FGln), has been used in the assessment of glutamine pool changes in patients with triple-negative breast cancer (TNBC). [12, 13, 14, 15, 16, 17]
A tracer with great promise is [18F]fluoroestradiol (FES), which can be used for whole-body assessment of estrogen-receptor status. The FDA approval of FES-PET was based on the excellent ability to predict estrogen-receptor expression status on pathology; patients with a positive FES-PET have estrogen receptors on immunohistochemistry. The presence of estrogen receptors is the only factor that can predict the effectiveness of endocrine therapy. [18, 19, 20]
Whole-body PET cameras are typically combined with a CT scanner to allow acquisition of anatomic and molecular information from a single procedure. These hybrid PET/CT cameras are donut-shaped. During the procedure, the patient is passed through the central hole of the camera. PET/CT cameras have the detector several centimeters away from the body surface, which limits scan resolution.
While PET/CT cameras are useful for whole-body imaging, breast-specific PET imaging, known as positron emission mammography (PEM), requires the PET camera to be configured like a mammography machine. PEM cameras utilize 2 small movable flat detectors that are pressed directly against the breast. [21, 22, 23] In a study of PEM alone, PET-CT alone, and combined PET-CT and PEM, the sensitivity rates were 72%, 60%, and 76%, respectively; specificity rates were 98%, 100%, and 98%, respectively; and accuracy rates were 85%, 79%, and 87%, respectively. [23]
The camera technology utilized by PEM has been shown to be more sensitive than whole-body PET/CT imaging in the detection of breast tumors. [1, 4]
Grade III multifocal infiltrating ductal carcinoma as seen on F-18 fluorodeoxyglucose positron emission tomography . This organ specific positron imaging technique results in a much higher resolution (down to 1 to 2 mm) compared to whole body PET/CT imaging.
Sueoka and associates compared the sensitivity of dedicated breast positron emission tomography (DbPET) with that of whole-body PET (WBPET) in detecting invasive breast cancer based on tumor size and biology. Results showed that the overall sensitivity of DbPET was higher than that of WBPET (91.4% vs 80.3%). Investigators concluded that DbPET is superior to WBPET in detecting subcentimetric, low-grade breast cancers. [24]
In a retrospective evaluation, Sasada and colleagues compared findings of WBPET and DbPET in patients with breast cancer according to the World Health Organization (WHO) classification of breast tumors. They reported that DbPET had high sensitivity and SUVmax values for all histologic types that showed low sensitivity of detection on WBPET, except lobular carcinoma in situ. [25]
Classification of breast tumors according to uptake patterns and metabolic parameters on ring-type DbPET has been shown to be useful for detecting breast cancer. Sasada et al investigated the performance of DbPET for incidental findings that were not detected by mammography and ultrasonography and found that uptake patterns, lesion-to-background ratio, and hereditary risk are useful for predicting breast cancer risk in incidental DbPET findings. [26]
In a study by Muduly et al of 45 patients who had undergone 18-FDG PET-CT scanning for breast cancer, there was a significant correlation of molecular subtype with SUVmax of the primary lesion. Higher primary SUVmax was associated with higher T stage and higher histologic grade. [27]
Indications
Positron emission mammography (PEM) is particularly useful when other imaging scan results are indeterminate. It has a useful complementary role to mammography, ultrasonography, and MRI.
PEM can assist in presurgical planning in breast cancer, monitoring response to therapy, and evaluating for tumor recurrence. In some cases, it may be useful in breast cancer staging and in helping guide breast biopsies.
PEM has a sensitivity and specificity of over 90% in the detection of primary breast cancer. [2]
This image demonstrates the ability of positron emission tomography to quickly assess response to chemotherapy, as early as 1 week after the first cycle. (Images courtesy of Mary K. Hayes, MD, Memorial Healthcare System, Hollywood, FL)
This image shows the ability of positron emission mammography to help ensure a breast biopsy is taken in the best location. The most metabolically active tissue needs to be evaluated for malignancy. The top image is obtained right before performance of the biopsy. The bottom image shows the biopsy needle to be properly positioned.
Complication Prevention
Because F-18 FDG releases radiation, caution is urged when using in pregnant women or in nursing mothers. [28] Women who are pregnant or breastfeeding will only rarely undergo a nuclear medicine procedure such as F-18 FDG PEM. Although F-18 FDG PEM has not been shown to cause any harm to the fetus or breastfeeding infant, caution is urged.
For pregnant women in whom the benefits of PEM are thought to greatly outweigh any potential risks, the physician may modify the dose of the radiotracer.
Women who are breastfeeding typically will stop breastfeeding for an hour or two after the PEM scan has been completed. After this, breastfeeding is resumed as normal.
Outcomes
When required, a PET-guided breast biopsy has been found to be safe, effective, and associated with only minimal to mild discomfort. [29]
The camera technology utilized by PEM has been shown to be more sensitive than whole-body PET/CT imaging in the detection of breast tumors. [1]
PEM has a sensitivity and specificity of over 90% in the detection of primary breast cancer. [2]
In a retrospective study, Satoh et al determined that whole-body total lesion glycolysis (WTLG) on FDG PET/CT images is an independent prognostic factor for survival in breast cancer patients who have metastases on initial presentation. [3, 30, 31]
Although very rare, hypersensitivity allergic reactions to the radiotracer can occur.
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Grade III multifocal infiltrating ductal carcinoma as seen on F-18 fluorodeoxyglucose positron emission tomography . This organ specific positron imaging technique results in a much higher resolution (down to 1 to 2 mm) compared to whole body PET/CT imaging.
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This image demonstrates the ability of positron emission tomography to quickly assess response to chemotherapy, as early as 1 week after the first cycle. (Images courtesy of Mary K. Hayes, MD, Memorial Healthcare System, Hollywood, FL)
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This image shows the ability of positron emission mammography to help ensure a breast biopsy is taken in the best location. The most metabolically active tissue needs to be evaluated for malignancy. The top image is obtained right before performance of the biopsy. The bottom image shows the biopsy needle to be properly positioned.
