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The Use of External Radioactive Markers in Scintimammography

KLEIN, MARTINE, M.D.*; WEININGER, JOLIE, Ph.D.; MOSHE, SINAIA, C. N. M. T.*; PERETZ, TAMAR, M.D.; CHISIN, ROLAND, M.D.*

Original Articles
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In Tc-99m MIBI scintimammography, the exact localization of foci of increased tracer uptake or the exact anatomic correlation of palpated breast masses with a scintigraphic finding is difficult. The authors describe three patients with known or possible malignant breast lesions for whom the use of external radioactive markers successfully helped to provide this information, thus improving the diagnostic accuracy and guiding decision-making in the patients’ treatment.

From the Departments of Medical Biophysics and Nuclear Medicine* and Oncology,‡ Hadassah University Hospital, Jerusalem; and Soreq Nuclear Research Center,† Yavne, Israel

Received for publication February 28, 2000.

Accepted July 23, 2000.

Correspondence: Martine Klein, M.D., Department of Medical Biophysics and Nuclear Medicine, Hadassah University Hospital, P.O.B. 12000, 91120 Jerusalem, Israel.

Breast self-examination, physical examination by a physician, and sequential mammograms are the primary screening tools used to detect breast cancer (1). Yet substantial limitations still exist in the use of mammography, such as dense and hyperproliferative glandular breasts, asymmetric opacities, and scarring from previous breast surgery (2). The low specificity of mammography (42%) is the primary explanation for the low biopsy yield: Only one biopsy in four is positive for breast carcinoma. In addition, the false-negative rates of mammography vary between 25% and 45% (3,4).

Scintimammography with Tc-99m MIBI, Tc-99m MIBI (Cardiolite; DuPont Merck Pharmaceuticals, North Billerica, MA) (5,6) has been proposed to complement mammography with equivocal findings and select those patients who may benefit from breast biopsy. Published results show good overall accuracy despite substantially different sensitivity and specificity for palpable and nonpalpable lesions (palpable: sensitivity approximately 80%, specificity approximately 75%; nonpalpable: sensitivity approximately 30%, specificity approximately 85%) (4,7).

The exact anatomic localization of a MIBI-positive area may be an objective problem. The result of planar imaging of breast volume is not always straightforward. In addition, mild tracer uptake, which may mimic a true abnormal finding, is often observed in the nipple. Conversely, for correlation purposes, the localization on the scintimammogram of a palpable finding is of utmost importance.

In 1 year at our institution, scintimammography was performed in 102 patients with possible primary or recurrent malignant breast lesions in which the results of palpation, mammography, or fine-needle aspiration were inconclusive. We used external radioactive Co-57 markers to resolve the problem of the exact localization of either the palpated mass or of the scintigraphic finding and of their correlation.

We present three cases that show the value of including external radioactive markers as part of a scintimammography protocol.

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Materials and Methods

The radiolabeling and quality-control procedures for the preparation of Tc-99m MIBI were performed according to the manufacturer’s instructions. All patients had a mammogram within 2 months before the scintimammogram. The breast was examined manually before injection. Each patient was injected in a dorsalis pedis vein. An average dose of 740 MBq (20 mCi) was injected and followed by a 10-ml normal saline solution flush.

Imaging was performed using a rectangular dual-head gamma camera (Elscint, Helix, Haifa, Israel) equipped with a parallel-hole low-energy, high-resolution collimator. The energy peak was centered at 140 keV with a 10% window. Data were recorded on a 64 × 64 matrix. Planar imaging was started 5 minutes after the injection of Tc-99m MIBI. Ten minutes or 3-million count anterior, lateral, posterior oblique, and medial views of both breasts were obtained in all patients. Anterior and medial views were acquired with the patient in the supine position. For the lateral and oblique views, the patient lay prone on a foam mattress with semicircular apertures in which the breasts were freely dependent. In all views, the arms were raised and the axillae were included in the field of view. Co-57 circular markers (100 μCi; DuPont Radiopharmaceuticals, North Billerica, MA) were used to correlate palpatory and scintigraphic findings. To identify a palpable nodule on the scintimammogram, an external radioactive marker was placed over the palpated nodule without moving the patient and a short acquisition image was obtained in a Co-57 window. This image was then superimposed on the corresponding scintigraphic view.

Conversely, when a focus of increased uptake was visualized on the scintimammogram, the corresponding area of the breast was localized with an external radioactive marker. The resulting Co-57 image was added to the corresponding scintigraphic view.

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Case Reports

Case 1

Breast carcinoma was diagnosed in a 33-year-old woman after fine-needle aspiration of a right axillary lymph node (ALN). At presentation, a small nodule was palpated posterior to the right nipple. Mammography failed to depict the nodule.

The lateral view of the Tc-99m MIBI scintimammogram showed a focus of increased tracer uptake in the right axilla and a second one posterior to the nipple (Fig. 1A). An external radioactive marker placed over the palpated nodule (Fig. 1B) corresponded to the scintigraphic finding behind the nipple (Fig. 1C). A biopsy of the nodule revealed adenocarcinoma of the breast.

Fig. 1

Fig. 1

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Case 2

A 62-year-old woman had, during a period of 5 years, repeated mammography, fine-needle aspirations, and an excisional biopsy of a palpated nodule in the upper outer quadrant of the right breast. All results were negative.

Subsequently, a right ALN was palpated and excisional biopsy of this lymph node revealed metastatic ductal breast carcinoma. Clinically, the primary tumor was thought to lie beneath the scar of the previous breast excision biopsy. However, different diagnostic methods produced conflicting results: mammography was again negative; magnetic resonance imaging showed a finding but could not differentiate between an ALN and a finding in the tail of the breast; and computed tomography showed a 3-cm right ALN.

Tc-99m MIBI scintimammography was performed to identify a possible primary localization under the scar. However, it showed only a focus of increased tracer uptake in the right axilla (Fig. 2A, anterior view;Fig. 3A, lateral view). External radioactive markers were placed over the palpated ALN (Figs. 2B and 3B, marker 1) and over the scar of the excisional biopsy of the breast (Figs. 2B and 3B, marker 2). The lateral view of the breast (Fig. 3B) allowed for better separation between the two markers than did the anterior view.

Fig. 2

Fig. 2

Fig. 3

Fig. 3

Superimposition of images A and B showed that the focus in the right axilla corresponded to the palpated ALN and that no focus of increased tracer uptake was visualized in the area beneath the scar (Figs. 2C and 3C).

Segmental resection of the upper outer quadrant of the right breast (including the area of the biopsy scar) and ALN dissection were performed and revealed metastatic ductal breast carcinoma in one ALN. No primary localization of the carcinoma was found.

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Case 3

One year after right mastectomy and ALN dissection for a differentiated infiltrating ductal carcinoma of the right breast (stage IIIA), chemotherapy, and radiation therapy, a 35-year-old woman presented with a palpable nodule in the upper inner quadrant of the left breast. Findings of repeated mammography of this large dense breast were negative.

Tc-99m MIBI scintimammography showed a focus of increased tracer uptake on both anterior (Fig. 4A) and medial (Fig. 5A) views. The anterior view suggested a finding in the left axilla. This focus was localized using an external radioactive marker (Fig. 5B, marker 1) and corresponded to the patient’s nipple. This marker correlated also with the finding on the medial view (Fig. 3D, marker 1). A second marker was placed over the palpated nodule (Figs. 4B and 5B, marker 2). No focus of increased tracer activity corresponded to this marker on either view (Figs. 4C and 5C).

Fig. 4

Fig. 4

Fig. 5

Fig. 5

The patient is free of disease after 3 years of follow-up.

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Discussion

In women younger than 50 years who have dense breasts, only 25% of the mammographic findings are proved positive on biopsy. Therefore, we need a noninvasive method to complement mammography and to help differentiate benign from malignant breast lesions. Furthermore, it has been shown that in 60% of patients with a false-negative result of mammography, scintimammography shows a finding compatible with breast cancer (7).

When the findings of mammography are negative but a lesion is palpable, it is important to know if performing a biopsy is worthwhile. Tc-99m MIBI scintimammography has a negative predictive value of 72% to 80%. The presence or absence of increased tracer uptake in a mass brings useful information (case 1, visualization of a finding not seen on mammography; case 2, no uptake in the area of possible recurrence under the scar of the previous biopsy).

When tissue diagnosis is obtained from a metastasis, usually an ALN, with no palpable breast finding and with a negative result of mammography, a positive result of scintimammography may be the only method to yield useful information (case 1).

In any case, the exact localization of the palpatory or of the scintigraphic finding is important, as illustrated by case 3, in which the scintigraphic finding was proved to be uptake in the nipple. This information may influence treatment decisions.

Other methods for localization have been suggested. Scintigraphy-guided biopsy of the breast is an invasive technique, and SPECT with reconstruction by iterative algorithms (8) did not show an added benefit compared with the planar method.

The use of external radioactive markers is a simple, noninvasive, patient-friendly, cost-effective method that improves the localization of breast masses and may be helpful in selected cases.

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References

1. Langer TG, Shaw de Parades E: Pitfalls in mammography. Applied Radiol 9: 13, 1990.
2. Jackson VP, Hendrick RE, Kerg SA, et al: Imaging of radiographically dense breasts. Radiology 188: 297, 1993.
3. Kopans DB: The positive predictive value of mammograms in patient with breast cancer. Am J Roentgenol 158: 521, 1992.
4. Mekhmandarov S, Sandbank J, Cohen M, et al: Technetium-99m MIBI scintimammography in palpable and non-palpable breast lesions. J Nucl Med 39: 86, 1998.
5. Khalkhali I, Mena I, Jouanne E, et al: Prone scintimammography in patients with suspicion of carcinoma of the breast. J Am Coll Surg 178: 491, 1994.
6. Kao CH, Wang SJ, Yeh SH: Technetium-99m MIBI uptake in breast carcinoma and axillary lymph node metastases. Clin Nucl Med 19: 898, 1994.
7. Palmedo H, Schomburg A, et al: Technetium-99m-sestamibi scintimammography for suspicious breast lesions. J Nucl Med 37: 626, 1996.
8. Tiling R, Tatsch K, Sammer H, et al: Technetium-99m-sestamibi scintimammography for the detection of breast carcinoma: comparison between planar and SPECT imaging. J Nucl Med 39: 849, 1998.
Keywords:

Breast Carcinoma; External Radioactive Markers; Tc-99m MIBI Scintimammography.

© 2001 Lippincott Williams & Wilkins, Inc.