**4. Radiation dose**

As with all nuclear medicine procedures, the detector systems do not emit radiation. The radiation dose delivered to the patient in these procedures comes from the radiotracer and is dependent on both the activity of the radiotracer injected and the biologic distribution of the tracer in the organs.

#### **4.1 BSGI/MBI radiation dose**

Sestamibi (MIBI) was cleared by the US FDA in 1991 for cardiac perfusion studies. In 1997, breast imaging was added as an indication to the drug package insert following a clinical trial conducted with standard gamma cameras equipped with high-resolution collimators. According to the drug package insert, the patient whole-body radiation dose is 4.8 milligray at 1110 megabecquerels (0.5 rads at 30 millicuries), see Table 4. According to the Dosage and Administration section of the drug package insert, breast imaging is to be conducted using a dose of 740 – 1110 MBq (20 – 30 mCi).

At the time of the US FDA approval, the breast imaging studies were being acquired with standard, large field-of-view gamma cameras, typical to a nuclear medicine department and the dose required for imaging was determined largely by the low photon sensitivity of these imaging systems when equipped with high-resolution collimators (Khalkhali et al., 2004) Since that time, several breast optimized gamma camera systems have been developed with significantly higher photon sensitivity and several studies indicate that it is possible to lower the injected dose of MIBI required for breast imaging with these systems.

A recent clinical trial was conducted to examine breast tissue uptake as a function of injected dose. The results of this analysis indicate that breast tissue uptake of MIBI appears to be linear relative to the injected dose thus implying there is no physiologic limitation to using lower doses (Böhm-Vélez et al., 2011). According to additional studies, conducted by the Mayo Clinic, the new, breast optimized detector systems provide a photon sensitivity roughly 3 times higher than that of the older imaging systems (Hruska et al., 2008).

From the available data, it is evident that these new detector technologies can reduce the dose required to conduct breast imaging with MIBI. Reducing the dose MIBI from 740 – 1110 MBq (20 – 30 mCI) to 259 – 370 MBq (7 – 10 mCi) reduces patient radiation exposure by nearly a factor of 3. The radiation exposure from a 259 MBq injection of MIBI is approximately 2 millisieverts (mSv) and is approximately equivalent to the radiation dose diagnostic breast patients receive from the combination of screening and diagnostic mammograms (Hendrick, 2010; Valinten, 2007).


Table 4. Radiation dosimetry of Sestamibi.

PEM detectors are tomographic imaging devices, an example image from the opposed detector system is provided in Figure 6. Note the noise level along the chest wall and the Z-resolution affect is expressed as a blurry, low intensity focus in the reconstruction planes outside of the plane the lesion is located in. In this particular case, it is most noticeable in the MLO projection images. There is noticeable residual blur in the area of the largest lesion in

As with all nuclear medicine procedures, the detector systems do not emit radiation. The radiation dose delivered to the patient in these procedures comes from the radiotracer and is dependent on both the activity of the radiotracer injected and the biologic distribution of the

Sestamibi (MIBI) was cleared by the US FDA in 1991 for cardiac perfusion studies. In 1997, breast imaging was added as an indication to the drug package insert following a clinical trial conducted with standard gamma cameras equipped with high-resolution collimators. According to the drug package insert, the patient whole-body radiation dose is 4.8 milligray at 1110 megabecquerels (0.5 rads at 30 millicuries), see Table 4. According to the Dosage and Administration section of the drug package insert, breast imaging is to be conducted

At the time of the US FDA approval, the breast imaging studies were being acquired with standard, large field-of-view gamma cameras, typical to a nuclear medicine department and the dose required for imaging was determined largely by the low photon sensitivity of these imaging systems when equipped with high-resolution collimators (Khalkhali et al., 2004) Since that time, several breast optimized gamma camera systems have been developed with significantly higher photon sensitivity and several studies indicate that it is possible to lower

A recent clinical trial was conducted to examine breast tissue uptake as a function of injected dose. The results of this analysis indicate that breast tissue uptake of MIBI appears to be linear relative to the injected dose thus implying there is no physiologic limitation to using lower doses (Böhm-Vélez et al., 2011). According to additional studies, conducted by the Mayo Clinic, the new, breast optimized detector systems provide a photon sensitivity roughly 3 times higher than that of the older imaging systems (Hruska

From the available data, it is evident that these new detector technologies can reduce the dose required to conduct breast imaging with MIBI. Reducing the dose MIBI from 740 – 1110 MBq (20 – 30 mCI) to 259 – 370 MBq (7 – 10 mCi) reduces patient radiation exposure by nearly a factor of 3. The radiation exposure from a 259 MBq injection of MIBI is approximately 2 millisieverts (mSv) and is approximately equivalent to the radiation dose diagnostic breast patients receive from the combination of screening and diagnostic

the injected dose of MIBI required for breast imaging with these systems.

all of the projections, including those outside of the lesion.

**4. Radiation dose** 

tracer in the organs.

et al., 2008).

**4.1 BSGI/MBI radiation dose** 

using a dose of 740 – 1110 MBq (20 – 30 mCi).

mammograms (Hendrick, 2010; Valinten, 2007).

Graph 1. The relative photon sensitivity of commercially available, breast-optimized imaging systems compared to that of the standard gamma camera.

#### **4.2 PEM radiation dose**

F-18 fluorodeoxy-D-glucose (FDG) was cleared by the US FDA in 2000 for a variety of uses including tumor localization. The total body radiation dose in FDG PET is 39 mrads per mCi injected activity (Table 5). According to the clinical literature, the typical FDG dose used for imaging with the standard whole body PET detectors ranges between is approximately 370 - 740 MBq (10 - 20 mCi).

The Role of Molecular Imaging Technologies in Breast Cancer Diagnosis and Management 191

**Overall** 96% **Invasive Cancers** 97% **Sub-centimeter lesions** 89% **Lobular Carcinoma** 93%

**DCIS** 94%

**Bertrand, 2009 Lee, 2011 Weigert, 2007**

**Sensitivity** 

**Total Patients** 1,042 662 512 **Sensitivity (%)** 91 95 89 **Specificity (%)** 77 88 90 **NPV (%)** 96 97 98

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

> **Overall** 90% **DCIS** 91% **ILC** 75% **Sub-centimeter** 63%

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

**5.2 Clinical evidence for PEM** 

compared to ductal carcinoma.

Table 8. Sensitivity of PEM by sub-group.

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

Table 6. The sensitivity of BSGI in various subgroups.

tissue.


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

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