Nuclear medicine has been i nvolved in the field of functional tumor imaging for decades. Its hallmark is the detection of viable tumor tissue based on functional and biological characteristics rather than on an altered tumor morphology. Scintigraphy has an important role in monitoring the response to therapy, by distinguishing active tumor mass, where the tumor-seeking tracer still accumulates, from residual mass composed of necrosis or scar, where tracer no longer accumulates. The use of scintigraphy in tumor detection depends on the mechanism of tracer uptake in the tumor, the pharmacokinetic and normal biodistribution of the tracer, and on the technology of the detecting system.

The detection of breast cancer using single-photon-emitting tracers with a gamma camera and positron-emitting tracers with PET technology has been an ongoing challenge of nuclear medicine [1]. The whole-body systems used originally in scintimammography were sub-optimal for the detection of small lesions in the breast, as the distance from the collimator to the breast is approximately 15 cm and to the region of interest up to 25 cm. Instead, dedicated systems for breast imaging were needed, which are now commercially available.

Gamma-cameras dedicated to breast imaging may be single- or dual-headed cameras; in the latter, each breast is positioned between the two detectors in two views similar to the acquisition mode on mammography, with no pressure. Detectors can be the NaI (Tl) detectors routinely used in nuclear medicine, a technology referred to as breast-specific gamma imaging (BSGI), or the new generation of pixilated semiconductor [cadmium zinc telluride (CZT)] detectors with improved spatial resolution. A dual-headed system composed of CZT detectors, the molecular breast imaging system (MBI), was reported to have a high sensitivity in the detection of clinically relevant breast lesions as small as 3 mm [2–4].

Several dedicated breast imaging systems for positron-emitting tracers have been designed. The earliest one, positron emission mammography (PEM), uses two oppositely placed detectors, as in mammography. With another prototype, dedicated breast PET, the patient is prone and the breast hangs freely through a small ring of detectors. The first system to become commercially available was a stationary flat detector-based PEM scanner that used limited-angle tomosynthetic reconstruction with a spatial resolution of 2.4 mm [5]. A newer design is mammography with molecular imaging (MAMMI), a dedicated breast PET system that uses a complete ring of detectors for full tomographic image reconstruction with a spatial resolution of 1.6 mm [6]. Dedicated breast PET systems were shown to be significantly more sensitive for the detection of breast cancer than either whole-body PET or PET-CT [7].

The tracer used for breast imaging with a gamma-camera is ^99mtechnetium (Tc)-sestaMIBI. The mechanisms of the enhanced cellular uptake of ^99mTc-sestaMIBI in cancer cells is the subject of ongoing investigation. ^99mTc-sestaMIBI is a small lipophilic cation whose uptake is nine times higher in tumor tissue than in normal tissue, reflecting the high vascularity and mitochondrial activity of the former [8, 9]. The major advantage of ^99mTc-sestaMIBI in breast cancer imaging is its wide availability in the routine practice of nuclear medicine departments, as it is also used in cardiac perfusion studies. Moreover, unlike PET tracers, it does not require cyclotron facilities for its production.

The most commonly used tracer for scintimammography with positron-emission technology is ¹⁸F-fludeoxyglucose (FDG). As a rule of thumb, ¹⁸F-FDG uptake is higher in breast tumors with prognostically unfavorable characteristics [10]. Primary tumor ¹⁸F-FDG uptake was found to correlate with tumor size, histological type and grade, pleomorphism, lymphatic invasion, high Ki-67 level, and triple negativity (i.e., negative for the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2) [11]. Yet, it should be borne in mind that ¹⁸F-FDG avidity is a characteristic of the individual tumor and some tumor types, such as ductal carcinoma in situ and lobular carcinoma, may show only low-intensity uptake [7, 12]. Moreover, when dedicated PET systems are used for breast imaging, heterogeneous uptake in a large tumor probably reflects tumor heterogeneity within the mass [13].

Publications on the clinical use of scintimammography have explored its role in tumor detection in patients with no known malignancies and as a diagnostic tool in patients with diagnosed breast cancer. The reported sensitivity of BSGI for the detection of breast cancer is 78–100% for all tumor types, including lobular carcinoma [2, 14]. Using the MBI system, researchers at the Mayo Clinic were able to detect small malignant lesions of 3 mm and calculated a sensitivity of 90% for abnormalities 5–20 mm in size. Scintigraphy was found to be a valuable procedure when routinely used screening modalities, mainly mammography, were suboptimal, such as in the case of patients with dense breasts. Based on the screening of 936 at-risk women, Rhodes et al., of the Mayo Clinic, reported a sensitivity of 27% for mammography alone and 91% for combined mammography and MBI [15]. This group reported the good performance of MBI with a low-dose of 8 mCi ^99mTc-sestaMIBI, with ongoing efforts aimed at dose-reduction to perform MBI with 4 mCi, with an effective dose twice that of a screening mammogram.

A recently published meta-analysis evaluated eight studies on the use of ¹⁸F-FDG-PEM, comprising 873 women with breast lesions. The pooled sensitivity and specificity values of PEM were 85% and 79%, respectively, according to a per-lesion-based analysis [16]. Currently, however, scintigraphy is not recommended as a routine screening tool because of the higher total body radiation compared to routinely used breast imaging modalities.

Accurate assessment of disease extent in the breast is essential to optimize the treatment approach in patients with newly diagnosed breast cancer. As in the case of MRI, scintimammography can identify additional, unexpected sites of disease, resulting in a change in diagnosis from localized to multifocal, multicentric, or even bilateral disease. In a retrospective study of 159 women with one suspicious breast lesion on physical exam and/or mammography, BSGI detected additional suspicious lesions in 29% and occult cancer in 9%, both in the same breast as the index lesion (6%) and in the contralateral breast (3%) [12].