Breast Cancer and the Role of Nuclear Medicine

Breast cancer statistics for 1998 from American Cancer Society estimate more than 182,000 new cases of breast cancer will be diagnosed during the year For women between the ages of it is the leading cause of death 1 out of every 9 women will be diagnosed with this disease

Early diagnosis Early treatment Reduced mortality

Two methods of screening for disease: Self examination and physical examination Mammography

Has a sensitivity between 15 to 20% Is less helpful with women who have: - Extremely dense breasts - Heterogeneously dense breasts - Surgically scarred breasts - Post radiation therapy fibrosis - Diffuse distribution of indistinct calcifications - Breast implants

Does nuclear medicine have a role in this? -Physiology vs. anatomy -What types of radio- pharmaceuticals might be available?

Tl-201 and tumor uptake -Blood flow -ATPase sodium potassium pump Calcium ion channel Leakage of immature tumor cells Reduced or no uptake in connective tissue containing inflammatory cells and necrotic tissue

Tc99m sestamibi (Miraluma) tumor uptake -First reported by in Campeau et al in 1992 (see references) -Uptake in tumor is a result of blood flow, mitochondria negative charge and density with tracer being positively charged

F18-FDG - Tumor has a great affinity for glucose -FDG is a glucose analog -Tumor to background is 3:1

Sestamibi clinical trials - For palpable mass -78% sensitivity -82% specificity - Non-Palpable mass -40 – 50% sensitivity -90 – 95% specificity

Non-palpable tumor and relation to size - Less than 1 cm the sensitivity was 20 – 30% - Greater than 1 cm the sensitivity was 60 – 70%

Tofani, et al evaluated 300 breast cancer patients tumor size 1 cm had a sensitivity of 95% (see references)

Clinical role of scintimammography according to Dupont Pharma (see references) -Not to be used in screening or to replace biopsy -According to Dupont Pharma, “Miraluma as a second line diagnostic drug after mammography to assist in the evaluation of breast lesions in patients with an abnormal mammogram or a palpable breast mass.”

It is specifically suggested for: - Palpable mass not seen on mammography - Increased size of mass on mammography - Change in contour of mass seen on mammography - Mass seen on mammography, but not on ultrasound - Mass developing in area of scar or previous surgical site - Increased number of previously demonstrated calcifications - Multifocal areas of clustered calcifications - Calcifications at surgical site

Procedure -Equipment setup - Small field of view camera with a LEHR collimator - Energy keV with a 10% window - Matrix – 128 x Acquisition time 600 seconds per view - Table overlay/matrix that has cutouts for breasts to be imaged in a prone dependent-breast position

Radiopharmaceutical administration - 25 mCi of Tc99m sestamibi - Inject IV into the contralateral arm of the suspected lesion - If bilateral disease is suspected the radiopharmaceutical should be injected into a leg vein

Imaging - Start imaging 5 minutes post injection - Patient should initially be in the prone position with the breasts inserted through the cutouts, in the “dependent-breast” position. - Breast should not be pinched at the base and note the angle of the nipple

- Lateral views of both breast should be taken - From the supine position have the patient place her arms behind her head and take an anterior view that would include both breasts and lymph nodes in the axillae

SPECT is not necessary recommended because of the amount of activity coming from the heart and GI tract

Negative For Breast Cancer

Breast Cancer Detected

Scinti-Camera Technology Current Auger cameras technology is a limiting factor in Reduced resolution Bulky size of detector has difficulty in positioning Need for smaller and more versatile detector

SPEM Single-Photon Emission Mammography Concept - Compact scintillation camera uses an array of discrete scintillator Crystals Matching array of photodiodes replaces PMTs and detects the scintillation light that results when a gamma ray is absorbed. Digital imaging where CsI(Tl) replaces NaI(Tl) Reduced camera/detector size Improved spatial resolution Compact size allows for closer and varied angles Less expensive system

Literature Results on SPEM SPEM was compared with a large field of view camera using Tc99m-sestamibi The small size of the detector head allows the use of mechanical breast compression to minimize detection distance and tissue scatter Found a 0.4 cm breast lesion that was missed on an Anger Camera

Still On the Drawing Board Small digital camera on a flexible arm Improves resolution Reduces background

Still On The Drawing Board This system has four digital imaging plates This movable plates can be adjusted Assume that there might also be some breast compression Better resolution and reduced background

Use of F18-FDG In comparison with Tc99m-sestamibi Mixed results Is F18-FDG the radionuclide of choice for the detection of breast cancer? However, the technology for imaging breast cancer also changed with the application of a specialized PET system

Current Technology – PEM Positron Emission Mammography Dilon Technology is on the left. They refer to their system and its technology as Molecular Breast Imaging (MBI) GE has also made a system which is displayed on the right and referes to the imaging as breast-specific gamma imaging (BSGI)

Dilon - BMI System employs breast compression along with the detection of coincidence detection of 511 keV photons This is an example where mammography picked up a calcification which turned out to be cancerous BMI identified two cancerous lesions which where verified by biopsy and MRI

Another Case from BMI Files Mammography identifies very dense breast tissue. Difficult to any specific breast mass MBI identified a mass which via biopsy is proven to be cancerous For more information visit

Can F-18FDG be useful in detecting/staging breast cancer? Scheidhauer et al - The accuracy of PET in the detection of primary breast cancer was 90%, and in the detection of involved axillary lymph nodes is 94%

Utech et al, stated, “In patients with breast carcinoma, 18F-FDG PET can be of value in evaluating axillary lymph nodes for metastatic involvement prior to surgery.”

In an article entitled, “Comparison of FDG-PET with MIBI-SPECT in the detection of breast cancer and axillary lymph node metastasis” it studied and compared FDG-PET to MIBI-SPECT. The authors concluded “Neither FDG-PET nor MIBI-SPECT is sufficiently sensitive to rule out axillary lymph node metastasis.

Regarding the use of chemotherapy and the role of FDG. Bassa and colleagues concluded, “FDG-PET is valuable for monitoring the effects of preoperative chemotherapy in patients with locally advanced breast cancer with better sensitivity for primary tumor and better specificity for nodal metastasis in comparison with ultrasonography.”

- Conclusion -Has the role of mammo- scintigraphy been clearly defined? - Where do we go from here?

References Miraluma: Kit for the Preparation of Technetium Tc 99m Sestamibi. (Version 2.0) (CD-ROM). (1997). Billerica, MA: Dupont Merck Pharmaceutical Company. Iraniha S, Khalkhali I, et al. Breast cancer imaging: can Tc-99m Sestamibi Scintimammography fit in? Medscape Womane’s Health (4) khalkhali.htmlhttp:// khalkhali.html Bassa P, Kim EE, Inoue et al. Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. Journal of Nuclear Medicine. 1996: 37(6): Campeau RJ. Kronemer KA. Sutherland CM. Concordant uptake of Tc-99m sestamibi and Tl- 201 in unsuspected breast tumor. Clinical Nuclear Medicine. 1992: 17(12): Yutani K, Shiba E, et al. Comparison of FDG-PET with MIBI-SPECT in the detection of breast cancer and axillary lymph node metastasis. Journal of Computer Assisted Tomography. 2000: 24(2): Tofani A, Sciuto R, et al. 99Tcm-MIBI scintimammography in 300 consecutive patients: factors that may affect accuracy. Nuclear Medicine Communications (12): Scheidhauer K, Scharl A, et al. Qualitative [18F]FDG positron emission tomography in primary breast cancer: clinical relevance and practicability. European Journal of Nuclear Medicine. 1996: 23(6): Utech CI. Young CS. Winter PF. Prospective evaluation of fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer for staging of the axilla related to surgery and immunocytochemistry. European Journal of Nuclear Medicine. 1996: 23(12): /14