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INVITED PERSPECTIVE

Is There a Clinical Role for in Diagnosis?

ported until now, the sensitivity and (5) reported a sensitivity of 62% for non- Scintimammography is the functional specificity of 99mTc-sestamibi scinti- palpable tumors and of 46% for ones Յ1 imaging study of the breast with single- in detecting primary cm, whereas the values for palpable and photon , such as were 83.8% and 86.4%, Ͼ1 cm were 98% and 96%, re- 99mTc-sestamibi or 99mTc-tetrofosmin. In respectively (3). spectively. 1994, Khalkhali et al. (1) reported the Despite these very encouraging re- Therefore, increasing the sensitivity first series with a relatively large number sults suggesting that scintimammogra- of planar scintimammography for of patients on the clinical application of phy could be a useful adjunct to mam- small-sized tumors is clinically very scintimammography. In their group of mography, the precise role of this relevant, and the role of SPECT in this 59 patients, in whom an abnormal mam- technique in the algorithm of breast task could be significant. Until now, mogram and physical examination war- cancer diagnosis and its specific clini- some discordant results have been re- ranted or fine-needle cytology of cal indications are still being debated ported in the studies comparing tomo- the breast, the sensitivity of scintimam- and are not definitively assessed. graphic and planar imaging in primary mography was 95.8%, specificity was In this issue of The Journal of Nuclear breast cancer diagnosis. These findings 86.8%, positive predictive value was , Mathieu et al. (4) present the are primarily attributed to the fact that 82.1%, and negative predictive value results of their investigations on the im- high-quality SPECT can be obtained was 97.1%. On the basis of these results, pact of scintimammography in a daily only with the patient in the supine po- the authors concluded that scintimam- practice, using this technique as a sec- sition and the arms up; prone SPECT is ond-line procedure in patients without a limited by geometric constraints of the See page 1574 definitive diagnosis after the first-line ex- patient, imaging table, and gantry (6), aminations, including palpation, mam- and the lower values are reported in the mography, ultrasound, and fine-needle studies in which tomographic images mography is very sensitive and able to aspiration. Therefore, this study evalu- are performed using this technique. In improve the specificity of mammogra- ated a difficult patient population, in a group of 63 patients with 67 mam- phy—so potentially useful to reduce the which scintimammography determined a mographically suspicious breast abnor- high rates of negative per- management modification in 49% of malities (7), we observed a sensitivity formed. After this investigation, numer- cases, analyzed in 4 different groups ac- of 93% for supine SPECT and of 86% ous studies have been published about cording to the clinical question. for planar imaging, whereas accuracy the clinical usefulness of scintimammog- When we look at the scintigraphic was 91% and 88%, respectively. More- raphy. The aggregated overall summary protocol, both planar and tomographic over, in breast lesions Յ1 cm, supine estimates of a recent meta-analysis se- acquisitions were performed, with the SPECT yielded a significantly higher lecting 64 unique studies (2), with data sensitivity of SPECT results signifi- sensitivity than planar images both in on 5,340 patients, including 5,354 breast cantly higher than that of planar im- T1b and nonpalpable breast cancers, lesions, were sensitivity, 85.2%; speci- ages—in particular, in the detection rate without any decrease in specificity (8), ficity, 86.6%; negative predictive value, of smaller lesions (4). This issue is of the thus indicating that SPECT acquisition 81.8%; positive predictive value, 88.2%; utmost importance: the ability to visual- is mandatory if scintimammography is and accuracy, 85.9%. It is worth noting ize small breast cancers is crucial for the performed for imaging small lesions. that 80% of the studies yielded sensitiv- development and acceptance of scinti- These clinical data are confirmed by a ity and specificity values of Ͼ80%, and mammography, because other breast im- breast phantom study demonstrating nearly half of them were values of aging modalities (mammography, MRI) that a better detection of small-sized Ͼ90%. Moreover, in Ͼ5,660 cases re- permit an early detection of small le- lesions is achieved with tomoscinti- sions. On the other hand, it is well graphic images than with planar im- known that planar scintimammography ages (9). Moreover, from a technical Received Jul. 7, 2005; revision accepted Jul. 11, 2005. has a low sensitivity for nonpalpable and point of view, these authors suggest For correspondence or reprints contact: Orazio Յ1 cm cancers, as indicated by several that SPECT should be reconstructed Schillaci, MD, University of Rome Tor Vergata, Viale G. Mazzini 121, 00195 Rome, Italy. reports. In particular, in a multicentric using iterative algorithms instead of E-mail: [email protected] study on 420 patients, Scopinaro et al. backprojection methods, and a 128 ϫ

CLINICAL ROLE OF SCINTIMAMMOGRAPHY • Schillaci 1571 128 matrix is preferable to a 64 ϫ 64 of all cancers that are Ͼ1 cm and some scintigraphic results in the group of one. Also, in a study including 113 additional tumor lesions not seen on patients studied for suspected recur- patients, Tiling et al. (10) have re- mammography (13). rence after treatment. Moreover, in the ported that SPECT with iterative re- What are the potential specific clin- false-positive cases, the mean time construction is superior to filtered ical applications of scintimammogra- interval between therapy and scintig- backprojection, showing both higher phy? Scintimammography is not a raphy was shorter than that in the rest sensitivity and specificity. screening procedure, but it could be of the patients. This aspect should be The main drawback of SPECT is useful as a complementary test when considered when performing scinti- that, despite its better contrast resolu- the first-line examinations are nondiag- mammography early after or tion, it can be difficult to obtain a pre- nostic, as indicated by Mathieu et al. , which may cause cise definition of the sites of radiophar- (4). In a multicenter trial enrolling inflammatory changes, whose pres- maceutical uptake, whereas prone 1,734 women, scintimammography ence demonstrated the decisive fac- lateral planar views provide natural sensitivity and specificity in the group tor for increased tracer uptake by be- landmarks of breast contours, which of patients with equivocal mammogra- nign breast lesions in a recent are useful for the localization of le- phy ( Reporting and targeted analysis of false scinti- sions. This limitation can be overcome Data System [BI-RADS] categories III graphic diagnoses (17). Therefore, to by the recent availability of hybrid and IV) were 88% and 91%, respec- avoid false-positive findings in pa- SPECT/CT systems, which allow— tively (14). In this study, the inclusion tients being evaluated for suspected through the coregistration of SPECT of in the algorithm of local relapse, scintimammography and CT images—the precise correla- breast cancer diagnosis caused a reduc- should be performed after an ade- tion of functional and anatomic data on tion of 62% in the number of unneces- quate time interval from treatment. the same image. The first clinical appli- sary biopsies and an 86% reduction in However, as suggested by Mathieu et 4 cations of this new technology in breast missed cancers. The most important al. ( ), the development of a scoring finding of these data is the capacity of system might also be of value to in- imaging indicate that SPECT/CT can in- scintimammography to significantly crease the specificity of SPECT in crease the accuracy of SPECT by a more increase the detection rate of breast this subset of patients, because accurate anatomic assessment of the cancer in a patient population with a 99mTc-sestamibi uptake was faint in sites of abnormal activity (11). low prevalence of disease. all their false-positive cases. If supine SPECT represents an easy- Because radiopharmaceuticals’ up- Finally, the possible role of scinti- to-perform technique to improve the sen- take is independent of the breast den- mammography in the identification of sitivity of breast scintigraphy, other op- sity, and the accuracy of scintimam- multifocal–multicentric breast cancer tions should be considered. Until now, mography is similar for fatty and dense and in the detection of the possible scintimammography has been usually (15), scintigraphy is indicated primary breast tumor in patients with ␥ performed with standard -cameras that for patients with a palpable mass not metastatic axillary lymph-node in- are large, bulky, and not specifically de- detected on mammography because of volvement must be considered. The signed for breast imaging. Dedicated dense breast tissue—in particular, detection of multicentric lesions is of small-field-of-view high-resolution cam- when the other diagnostic tests are in- the utmost importance, because it can eras can allow greater flexibility in pa- conclusive. Furthermore, scintimam- alter the surgical management of the tient positioning (it is possible to acquire mography is particularly useful in pa- patient (i.e., total instead the scintigraphic images in the same tients with doubtful microcalcifications of quadrantectomy). It has been re- mammographic views) and breast com- or parenchymal distortions, in the pres- ported that scintimammography is pression, increasing the target-to-back- ence of scar tissue after surgery or able to assess the presence of multi- ground ratio. In fact, the detector can be biopsy and in breasts with implants focal–multicentric disease, as to de- placed directly against the chest and a (16). It’s well known that mammogra- tect bilateral breast cancers, with mild compression reduces breast thick- phy is less accurate in evaluating higher sensitivity when compared ness and improves the camera’s sensitiv- breasts that have been previously sub- with mammography or ultrasound ity. Moreover, by design, the breast cam- mitted to surgery, biopsy, radiation (18). However, because of the lim- eras are also able to provide better therapy, or . Patients ited data available in this specific intrinsic and extrinsic spatial resolution who have a scar within the breast due application, together with the low than conventional cameras, with an en- to these iatrogenic interventions are sensitivity of scintimammography in hancement in contrast resolution of often difficult for mammographic in- visualizing small additional malig- small lesions (12). Using a dedicated terpretation, whereas scintimammog- nant lesions (19), this potential indi- camera for breast imaging, a sensitiv- raphy is not affected by these morpho- cation deserves further studies in a ity of 86% has been recently achieved logic changes. Nevertheless, it is worth larger series; moreover, the good per- in detecting malignant lesions that are noting that Mathieu et al. (4) have re- formance of MRI in this field should Ͻ1 cm, together with the visualization ported the highest rate of false-positive be considered (20). In patients with

1572 THE JOURNAL OF • Vol. 46 • No. 10 • October 2005 axillary lymph-node metastases attrib- precise clinical applications to readily 99m-sestamibi scintimammography for the detec- tion of breast carcinoma: comparison between pla- uted to adenocarcinoma, but negative become routine. nar and SPECT imaging. J Nucl Med. 1998;39: mammography and ultrasound, scinti- 849–856. mammography may be useful for de- Orazio Schillaci, MD 11. Schillaci O, Danieli R, Manni C, Simonetti G. Is SPECT/CT with a hybrid camera useful to improve tecting the possible primary tumor in University of Rome Tor Vergata scintigraphic imaging interpretation? Nucl Med the breast. Nevertheless, also for this Rome, Italy Commun. 2004;25:705–710. application, until now there has been 12. Brem RF, Schoonjans JM, Kieper DA, Majewski S, REFERENCES Goodman S, Civelek C. High-resolution scinti- insufficient evidence for recommend- mammography: a pilot study. J Nucl Med. 2002; ing breast scintigraphy. The use of 1. 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