Positron emission mammography (PEM) produces a 3-D tomographic view of the breast in 12 images per view. Photo courtesy of Naviscan.
The last 20 years have brought about great advances in breast cancer detection and treatment. Among them has been the advent of molecular breast imaging tools, based on either gamma technology — breast-specific gamma imaging (BSGI)/molecular breast imaging (MBI) — or high-resolution positron emission tomography (PET) technology — positron emission mammography (PEM). These tools differ from those traditionally used in breast imaging, as they do not evaluate anatomy, as is the case with mammography, ultrasound and magnetic resonance imaging (MRI).
The techniques are similar, in that cancerous cells demonstrate both increased blood flow, as indicated by sestamibi uptake with BSGI/MBI and glucose through F18-fluorodeoxyglucose (FDG) uptake with PEM. Although both exams are currently marketed as “molecular breast imaging,” some have challenged this categorization because sestamibi uptake functions much like MRI, imaging blood flow rather than molecular metabolic activity imaged using PET.
Images for both studies are acquired with the patient seated upright, mimicking standard mammographic views. Interpretation of both exams is much faster than MRI, as fewer images are produced per study. False positives, such as fibroadenomas, are seen on BSGI and PEM, but less frequently than with MRI. PEM can be followed with whole body PET imaging to evaluate for metastatic disease using the same injection of FDG. Both procedures can take up to 40 minutes per exam, and both involve ionizing radiation.
Pros and Cons of BSGI/MBI
BSGI/MBI is breast scintigraphy using either a single- or dual-headed small-field-of-view gamma camera and (99m)Tc-sestamibi (Cardiolite). The technique uses planar single photon emission radionuclide imaging with a cardiac imaging agent and produces a single one-dimensional image per view, similar to mammography. There is increased mitochondrial uptake in cancer cells by sestamibi due to increased vascularity at a certain tumor size which is not impacted by breast density.
The device has been cleared by the U.S. Food and Drug Administration since 1999 and is used mostly as an adjunct to mammography to help differentiate scar tissue from cancer recurrence in patients with prior diagnosis, to screen high-risk patients who are contraindicated for MRI and to help patients with indeterminate findings on mammography. A biopsy accessory for single-headed cameras was cleared by FDA in late 2009, although only a handful of centers performing BSGI have adopted biopsy to date.
Small retrospective studies have shown a sensitivity of 88.5 percent for sub-centimeter cancers and 93 percent for invasive lobular carcinoma, although neither study was statistically significant. Recent prospective trials indicate a sensitivity of 88.8 percent and a specificity of 90 percent for primary lesions ? 1 cm and a sensitivity of 29 percent for lesions smaller than 5 mm.
Dose is a concern with BSGI/MBI, given that the technology is most commonly deployed in a screening population. BSGI requires a dose of 25 mCi of (99m)Tc-sestamibi, and imaging must occur immediately following injection as the radiotracer tends to wash out, especially for aggressive and chemo-resistant cancers.
The published guidelines by the Society of Nuclear Medicine propose a 25 mCi dose of sestamibi, although there are ongoing trials underway to look at dose reduction with dual-headed BSGI/MBI cameras. The currently approved dose results in 830 mrem of radiation exposure to the patient or 1.5 times the average yearly exposure in the United States. Future reduced dose of sestamibi will require off-label use, as the FDA drug labeling currently indicated for breast imaging with this radiotracer is 20-30 mCi. Radiation dose to the technologist is also a concern, given that positioning and imaging of the patient occurs immediately post-injection.
As with breast MRI, BSGI/MBI studies in pre- and peri-menopausal women must be timed appropriately with the patient’s menstrual cycle. An additional challenge is the lack of breast or cancer-specific radiopharmaceuticals for this tool, since sestamibi was developed specifically for cardiac imaging. There do not appear to be any new radiotracers for this type of camera currently available clinically or through research protocols at this time.
Pros and Cons of PEM
PEM, the breast application of a high-resolution PET scanner, has emerged since its FDA clearance in 2003 as a viable advanced imaging technique to help with presurgical planning and staging, to evaluate axillary lymph nodes, to monitor response to neoadjuvant chemotherapy and to look for recurrent disease. A biopsy capability using existing MRI vacuum-assisted techniques was approved in 2008 and has a high adoption rate.
PEM produces a 3-D tomographic view of the breast in 12 images per view. Early studies comparing the results of PEM with pathology showed a sensitivity of 90 percent as well as a high specificity of 86 percent in evaluating known breast cancer or suspicious lesions. Other studies have shown that PEM has a positive predictive value for biopsy of 83 percent when compared to 74 percent for MRI with no statistically significant difference in sensitivity and specificity.
A larger prospective multicenter study showed PEM and MRI to be equally sensitive and specific for detection of primary lesions, but PEM was more specific than MRI for detection of secondary smaller lesions and had a higher PPV. PEM’s higher specificity shows a potential to reduce false positives compared to other advanced breast imaging modalities.
PEM requires a high-resolution PET scanner and injection of 5 mCi of 18F-FDG, a minimum of 60-minute uptake time with a fasting glucose level of <140 mg/dl. No specific timing is required, as the radiotracer is not impacted by hormonal perturbations. It should be performed by a dedicated team, which can include either radiologists experienced in mammography and image-guided biopsy techniques or nuclear medicine physicians. The availability of PEM-guided vacuum-assisted biopsy is essential for centers performing PEM to confirm lesions not seen on any other modality, given the scanner’s 1.6 mm resolution.
As this technology is PET, new breast cancer-specific radiotracers, such as fluorine-18 16?-fluoroestradiol (FES), and tracers developed to identify proliferating and non-proliferating tumors, like [18F] fluorothymidine (18F -FLT) and Cu-64, are currently used on this device to monitor response to neoadjuvant chemotherapy. These radiotracers are available only in clinical trials under IND in the U.S., but are in clinical use with PEM in other countries.
Dose is also a concern with PEM. Since it is typically deployed after an initial diagnosis of cancer, the risk-to-benefit ratio should be adjusted accordingly. Recent studies have validated a reduced dose of 5 mCi of FDG per exam, resulting in 350 mrem of radiation exposure to the patient or about half the average U.S. yearly exposure. Dose to the technologist with PEM is lower than with BSGI/MBI, as patients are imaged post-void, one hour after injection.
In the United States, PEM is not currently deployed as a screening tool and may only be used post-diagnosis. BSGI/MBI is often used both pre- and post-diagnosed, and many centers have taken advantage of Henda’s Law to deploy the technology for problem-solving equivocal mammograms in dense-breasted patients. These studies are only reimbursed if BI-RADS 0 is given on a mammography report.
Conclusion
Although breast MRI is well-suited to image patients at high risk for breast cancer, it is estimated that 15 percent of women cannot tolerate this procedure due to severe claustrophobia, body habitus, kyphosis or other contradindications. For this reason, BSGI or PEM may help guide breast evaluation in selected patient populations.
As with breast MRI, findings from these molecular imaging tools should not be substituted for histological tissue diagnosis, especially when the patient and her surgeon are considering breast conservation. The decision to use these tools as an adjunct to the evaluation of patients with breast cancer should be made by the physician and the patient after joint consideration of the benefits as well as the risks associated with exposure to radiation. Neither BSGI/MBI nor PEM should replace mammography for yearly screening exam in the general population, given the cost to the healthcare system and the radiation exposure.
Parvez Shirazi, M.D., is founder of Golf Diagnostic Imaging Center, a multi-modality imaging center located in the Chicago area. He is also professor of nuclear technology at King Edward Medical College in Lahore, Pakistan, associate professor at Loyola University Chicago and is adjunct faculty at the University of St. Francis in Joliet, Ill.
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April 15, 2024 
