**5. Clinical evidence**

There is a substantial history of clinical literature on imaging breast cancers with nuclear medicine techniques. One of the first reports of breast imaging using MIBI was provided by Campeau and his colleagues in 1992 while the first report of breast cancer imaging using FDG was reported by Wahl the previous year (Campeau et al., 1992; Wahl et al,. 1991) Since that time, hundreds of articles have been published on breast imaging using these radiotracers. However until recently, these imaging studies were conducted with large gamma cameras typical in the nuclear medicine department. The development of breastoptimized detector systems used in BSGI/MBI and PEM is more recent and the primary advantage of these systems is that they provide higher sensitivity for the detection of breast lesions than their predecessors.

#### **5.1 Clinical evidence for BSGI/MBI**

There have been several clinical studies evaluating BSGI/MBI in breast cancer detection. In 2008, the group from George Washington Medical University provided an overview of their experience using BSGI/MBI in 146 patients who participated in an IRB approved trial (Brem et al., 2008). Table 6 provides the reported sensitivity of BSGI for various subgroups from that analysis.


Table 6. The sensitivity of BSGI in various subgroups.

190 Imaging of the Breast – Technical Aspects and Clinical Implication

The dose of FDG used for PEM studies has generally followed the guidelines established with the lager systems, typically using approximately 444 MBq (12 mCi) (Berg et al, 2006). However, more recent studies have demonstrated that doses of 111 – 185 MBq (3 – 5 mCi) are possible with the breast-optimized imaging systems (MacDonald et al, 2010). The resulting radiation dose to the patient is 1.9 – 3.1 mSv using a low dose protocol, nearly

There is a substantial history of clinical literature on imaging breast cancers with nuclear medicine techniques. One of the first reports of breast imaging using MIBI was provided by Campeau and his colleagues in 1992 while the first report of breast cancer imaging using FDG was reported by Wahl the previous year (Campeau et al., 1992; Wahl et al,. 1991) Since that time, hundreds of articles have been published on breast imaging using these radiotracers. However until recently, these imaging studies were conducted with large gamma cameras typical in the nuclear medicine department. The development of breastoptimized detector systems used in BSGI/MBI and PEM is more recent and the primary advantage of these systems is that they provide higher sensitivity for the detection of breast

There have been several clinical studies evaluating BSGI/MBI in breast cancer detection. In 2008, the group from George Washington Medical University provided an overview of their experience using BSGI/MBI in 146 patients who participated in an IRB approved trial (Brem et al., 2008). Table 6 provides the reported sensitivity of BSGI for various subgroups from

Table 5. Radiation dose for FDG based on 1 mCi injection.

identical to that of low dose BSGI/MBI (O'Connor et al., 2010).

**5. Clinical evidence** 

lesions than their predecessors.

that analysis.

**5.1 Clinical evidence for BSGI/MBI** 

Other, larger studies have provided evidence of high sensitivity and specificity for BSGI. The first of these larger studies was an analysis performed by Weigert and her associates in more than 500 women who had a BSGI scan performed as part of their routine diagnostic imaging following conventional imaging (Weigert et al., 2007). It is interesting to note that over half of the patients in this study had indeterminate findings following mammography and ultrasound. Two years later, Bertrand presented the results from a retrospective, multicenter study reporting that BSGI provided a higher sensitivity than diagnostic mammography in detection of breast cancer, especially in the high-risk and dense breast populations (Bertrand et al., 2009) Last, in 2011, Lee et al reported that BSGI had a higher sensitivity than mammography and higher specificity than ultrasound in their series of 622 patients who had all three imaging modalities performed as part of their diagnostic examination (Lee et al., 2011). In addition, this work found that there was no change in the sensitivity of BSGI between normally dense and heterogeneously or very dense breast tissue.


Table 7. The clinical performance of BSGI from several studies.

#### **5.2 Clinical evidence for PEM**

One of the earliest published studies on PEM containing a group of 77 patients examined the effectiveness of PEM in the detection of breast carcinoma (Berg et al., 2006). Table 8 provides the sensitivity of PEM as determined by this work. As expected, the sensitivity for lobular carcinoma was somewhat lower potentially due to the reduced glucose metabolism compared to ductal carcinoma.


Table 8. Sensitivity of PEM by sub-group.

The Role of Molecular Imaging Technologies in Breast Cancer Diagnosis and Management 193

In June of 2009, an interdisciplinary committee established by the American College of Surgeons published a report to provide guidance on the use of imaging techniques in breast patients (Silverstein et al., 2009). This panel grouped BSGI/MBI and PEM together as


In June 2009, the Society of Nuclear Medicine released the Procedural Guidelines for Breast Scintigraphy with Breast-Specific Gamma Cameras that included several proposed several indications for BSGI/MBI (Goldsmith et al., 2009). The indications are quite specific and echoed those set forth by the American College of Surgeons. The indications can be grouped

1. As a diagnostic adjunct for patients with indeterminate findings on conventional imaging (mammography, ultrasound and/or MRI) and remaining diagnostic concerns

2. Preoperative treatment planning in patients with a known cancer diagnosis to determine the extent of the primary lesion and to detect additional foci of disease. 3. As an alterative to breast MRI for patients whom MRI is indicated, but not possible;

There are no additional published guidelines for PEM other than those of the American

1. Pre-operative treatment planning in patients with a known cancer diagnosis to determine extent of the primary lesion and to detect additional foci of disease.

3. As an alternative to breast MRI in patients for whom MRI is indicated, but not possible;

BSGI/MBI and PEM are adjunctive molecular breast imaging technologies which are becoming more common in the breast center and they provide very similar performance in terms of sensitivity and specificity. The radiation dose associated with these imaging techniques is similar to that patients receive from other diagnostic imaging procedures such

2. To monitor the response of breast tumor(s) to neoadjuvant chemotherapy.

molecular imaging techniques and issued the following recommendation:

useful as an additional problem-solving tool in some situations."

such as palpable mass, nipple discharge, pain, etc.

4. Monitoring tumor response to chemotherapy.

**7.2 Recognized PEM indications** 

**8. Conclusion** 

ferromagnetic implants, compromised renal function, etc.

College of Surgeons that essentially provided three indications:

ferromagnetic implants, compromised renal function, etc.

**7.1 Recognized BSGI/MBI indications** 

into 4 primary categories.

The overall sensitivity and specificity for PEM is very good, especially for DCIS. Table 9 lists for each of the four PEM studies cited, the total number enrolled, the sensitivity, specificity, and negative predictive value.


Table 9. Clinical results of PEM imaging. NR = not reported.

In clinical studies of BSGI/MBI and PEM, both of these metabolic imaging modalities provide improved sensitivity and specificity for the diagnosis of breast cancer compared to mammography alone. The sensitivity and specificity of BSGI and PEM are generally comparable with both modalities demonstrating the capability to visualize lesions as small as 1 – 2 mm. Both PEM and BSGI/MBI systems have biopsy guidance capabilities.

## **6. Clinical considerations**

Both BSGI and PEM provide valuable clinical information in the detection and treatment of breast carcinoma. Like all imaging studies, each has distinct advantages and limitations. From the clinical data, it is evident that the performance of these modalities is quite comparable.

The biggest differences between the procedures are logistical. First, in most areas, MIBI is more readily available and significantly less expensive than FDG. In addition, the shorter half-life of FDG puts tighter constraints on the clinical schedule. For example, if a patient arrives 1 hour late for a FDG injection, the dose has lost 32% of the intended activity where as a MIBI dose has lost 9%. Also, the use of FDG requires four hours of patient fasting prior to injection and MIBI does not have this constraint. FDG also requires a 1-hour post-injection delay for imaging where as MIBI imaging can begin immediately post injection. Based on the injection-to-imaging time considerations, total time required for a MIBI study is approximately 45 minutes compared to approximately 2 hours for an FDG study.
