Molecular Breast Imaging Mammography: The Probllem
Michael O ’Connor, PhD Department of Radiology Mayo Clinic Rochester, MN
This work has been funded in part by the following: National Institute of Health Dept. of Defense Breast cancer and Cancer clearly visible Cancer would be occult Susan G Komen Foundation tumors appear white in non-dense breast in dense breast on mammogram Mayo Foundation Sensitivity Sensitivity Friends for an Earlier Breast Cancer Test 80%-90% 40%-70%
Breast Cancer Sensiitiiviity of MMG, US, and MRI Comparatiive Rellatiive Riisks iin Women at Increased Riisk
Subjjectts Sensiittiiviitty Sensiittiiviitty Sensiittiiviitty Riisk factor Rellatiive riisk Autthorr//yearr Counttrry ((no..)) MMG ((%)) US ((%)) MRII ((%)) BRCA muttattiion 20 Kuhll ,, 2000 Gerrmany 192 33 33 100 Lobullar carciinoma iin siittu 8-10 Dense breastt parenchyma 4-6 Warrnerr,, 2004 Canada 236 36 33 77 Personal history of breast cancer 3-4 Personal history of breast cancer 3-4 Krriiege ,, 2004 Nettherrllands 1,,909 40 NA 71 Famiilly hiisttory ((1 ° rellattiive)) 2..1 Kuhll ,, 2005 Gerrmany 529 33 40 91 Posttmenopausall obesiitty 1..5 Prempro ((WHII)) 1..26 Leach 2005 U..K.. 649 40 NA 77
Sarrdanellllii ,, 2006 IIttally 3571 40 43 81
1 Amerriican Cancerr Sociietty MRI: Maiin Diisadvantages New guidelines issued on March 28 th , 2007 Compllexiitty Recommend annual MRI screening for women with a high lifetime ri sk of •• Typiicall conttrrastt enhanced brreastt MRII may conttaiin overr 1500 breast cancer – defined as 20% or more iimages
Costt (Mediicare reiimbursementt ratte) June 2008 •• Anallog Mammogrram ~$90 •• Diigiittall Mammogrram ~$140 •• Biillatterrall brreastt ullttrrasound ~$200 •• Biillatterrall MRII > $1,,000
Speciiffiiciitty •• ((tterrttiiarry centterrs)) ~ 90% •• ((communiitty centterrs)) ~ 50%
Nucllear Mediiciine / Mollecullar Imagiing IImpactt off Tumor Siize on Mettasttattiic Diisease Sciinttiimammography <10 mm: 5 -year survival = 98% • Tc --99m sesttamiibii apprroved by tthe FDA fforr brreastt iimagiing 30 mm : 5 -year survival = 70% iin 1997 90 Aust. Inst. Health Welfare, Oct 2007 • Severrall llarrge mullttiicentterr sttudiies underrttaken iin llatte 1990s 7700% 6600% Taiillllefferr :: Sem Nucll Med 29::16,, 1999 60 5522% ((2009 pattiientts)) % wiitth 4455% Sensitivity = 85%, specificity = 89% Mettassttattiicc 3333% Sensitivity = 85%, specificity = 89% Diisseasse 30 2200% Brem : J Nucl Med 43:909, 2002 Sensitivity 35 -64% for lesions <1 cm 0 Taillefer : Sem Nucl Med 29:16, 1999 <0.5 0.5 -1.0 1-2 2-3 3-4 4-5 >5 Sensitivity ~55% for masses <1.5 cm Tumorr siize ((cm))
2 Conventionall Sciintiimammography Small Field of View Gamma Cameras
Diigiirad Diillon IInc.. CZT Technollogy Mullttiicrrysttall Mullttiicrrysttall Cadmiium Ziinc Cesiium IIodiide Sodiium IIodiide Tellllurriide ((CZT)) + Phottodiiodes + PMTs Semiiconducttorr
Breast Phantom: Comparison between Systems* Cadmium Zinc Telluride (CZT) Detector *Hruska CB, et al. Nucl Med Commun , 2005; 26: 441 -445
Tumor Depth 2.54 cm
1cm
• Excellent Intrinsic Resolution = 1.6 mm
3 cm • Excellent Energy Resolution 4.0% • Can be operated at room temp
• No dead space – ideal for breast imaging
• Expensive – currently limited to small 5 cm field of view detectors • First commercial gamma cameras using MC -NaI NaI CZT MC -CsI CZT developed for nuclear cardiology
3 Energy Resolution - CZT Detector Mollecullar Breast Imagiing – 2009
MBI Prototypes developed at Mayo over last 6 yrs using detectors from Gamma Medica and GE Healthcare Cadmium Zinc Telluride (CZT) gamma camera technology • Expensive – currently limited to small field of view detectors Dual -detector design optimized for breast imaging Anticipated cost ~$400 / study
Dual -detector MBI System
Can MBI find small breast tumors? How does Molecular Breast Imaging Work? Can MBI find small breast tumors?
Patient receives an IV injection of a radiotracer (Tc -99m sestamibi) The tracer preferentially accumulates in cancer cells and is not influenced by breast density The breast is lightly compressed between the 2 MBI gamma cameras, only light pain -free compression is necessary Imaging starts ~5 minutes post injection. Acquire CC and MLO views of each breast for 10 minutes / view Procedure performed by nuclear medicine technologist trained in mammographic positioning techniques
4 Compariison off Screeniing MBII and
Vol 191, 1808 -1815 Mammography
~1000 pattiientt scrreeniing sttudy Technology Tumors 5 -10 mm Tumors < 5 mm All Tumors (128 Funded by Susan G Komen Foundattiion in size in size in 88 patients) Comparre MBII and mammogrraphy iin pattiientts wiitth dense breasts at high risk of breast cancer Standard γ-Camera* 55% No data dense breasts at high risk of breast cancer Prriiorr hiisttorry off brreastt cancerr Single -head MBI 76% 44% 82% Famiilly hiisttorry iin one FDR orr ttwo SDR Dual -head MBI 87% 67% 90% Gaiill lliiffettiime rriisk > 20% *Palmedo et al: EJNM 25:375, 1998 Prriiorr attypiia orr LCIIS
Questtiion – iis MBII a viiablle scrreeniing adjjunctt tto mammogrraphy iin pattiientts wiitth dense brreastts?
18 mm 10 mm 8 mm 5 mm 3 mm
Results Screening Patient Examples (1) In 958 patients studied, a total of 14 cancers in 12 patients were diagnosed. Rt CC Rt MLO • 8 cancers detected by MBI alone • 1 cancer detected by mammography alone • 2 cancers detected by both MBI and mammography
100 79 % (11 / 14) 71 % (10 / 14) 80
% of 60 Cancers Detected 40 21 % (3 / 14)
20 Digital Screening Mammography (Negative) 0 MMG MBI Combination Molecular Breast Imaging (Positive) Imaging Modality 17 mm IDC with DCIS extension
5 Screening Patient Examples (2) A L R MBI P Digital Screening vs.vs. Mammography SPECT (Negative) SPECT
Molecular Breast Imaging Rt MLO (Positive)
Parathyroid scan with Tc -99m sestamibi performed 4 weeks prior to MBI study in Screening Patient Example #3 9 mm Ductal Carcinoma In Situ
Screening Patient Examples (3) Screening Patient Examples (4) Lt CC Lt MLO
Digital Screening Mammography (Negative)
Molecular Breast Imaging (Positive)
Digital Screening Mammography (Negative) Rt MLO Molecular Breast Imaging (Positive) 9 mm Invasive Ductal Carcinoma 7 mm Tubulolobular Carcinoma
6 Results in 958 Patients with 12 -month Follow -up Molecular Breast Imaging in Patients undergoing Myocardial Perfusion Imaging Sensiittiiviitty:: Allll cancerrs dettectted by any means iin tthe 12 --montth perriiod siince tthe MBII sttudy.. MBIs performed in women presented for myocardial 10 // 14 cancerrs dettectted by MBII perfusion studies, no additional dose needed (sensitivity = 71%) (sensitivity = 71%) Of 158 patients 3 // 14 cancerrs dettectted by mammogrraphy • 3 cancers detected, 1 only detected by MBI (sensitivity = 21%) (sensitivity = 21%) • 1 patient with uptake in papilloma and atypia • 154 patients with negative findings
Speciiffiiciitty:: Pattiientts wiitth a negattiive ffollllow --up mammogrram att 1 yearr and Negative screening mammogram no clliiniicall sympttoms att 12 --montths werre assumed tto be diisease ffrree Myocardial perfusion scan and MBI 1 week later Specificity - MBI 93% Recall Rate – 7.5 % Specificity - MBI 93% Recall Rate – 7.5 % Follow -up Dx mmg /US positive, 8 mm IDC/DCIS Speciiffiiciitty -- mammogrraphy 90% Recallll Ratte – 9..2 % IDC/DCIS Breast MRI correlated with MBI
MBI - Potential Screening Application MBI - Limitations and Disadvantages MBI has 2 -3 times sensitivity of mammography in the high -risk and dense breast populations False positive findings in some cases of MBI appears to have comparable sensitivity (80%) to that reported for MRI in women at increased risk of fibroadenomas, papillllomas, fat necrosiis. breast cancer American Cancer Society guidelines recommend Uptake of Sestamibi is influenced by hormonal annual MRI if lifetime risk exceeds 20%: would impact changes up to 1.5 million women annually in the U.S. Cost of MBI estimated at ~1/5 th cost of Breast MBI MBI - high radiation dose relative to Currently no clinical systems available mammography - First clinical systems in late 2009 ?
7 Cumulative Cancer Incidence per 100,000 women from annual MBI: Implications for Radiation Exposure to the screening with Mammography or Tc -99m sestamibi starting at age 40 MBI: Implications for Radiation Exposure to the
3500 Technologist from 8 patients / day, 20 mCii / patient
0 3000 0 0 , 0
0 500 1
2500 /
e c
n 400 e 2000 d i
c 2 - 4 mCi Sestamibi n I
r Mammogram 3.8 – 6.6 mGy 300 e 1500 MBI c 25 mCi Sestamibi mrem
n Tech a Background Radiation C
e 200 1000 v i t a l u 100 General Cardiology m 500 NMT u NMT Radiographer C
0 0 40 45 50 55 60 65 70 75 80 Annual Technologist Dose Age (years)
MBI – Radiation Dose MBI Dose Reduction 20 mCi Dose 4 mCi Dose Radiation risk to patients / technologists Upper Rt. MLO Upper Rt. MLO MBI with 20 mCi Tc -99m sestamibi = 6.5 mSv Rt. MLO Mammogram is < 1.0 mSv Combined/filtered Dose reduction techniques have been developed to reduce administered dose of Tc -99m sestamibi to 2 -4 mCi - collimator optimization - energy window optimization - noise reduction algorithms - composite image from opposing detectors Lower Rt. MLO Lower Rt. MLO
8 MBI - Future Directions Mollecullar Breastt IImagiing Futturre Devellopmentts – New Radiiopharrmaceuttiicalls Clinical applications Tc --99m Sesttamiibii Tc --99m Bombesiin Screening in high -risk women • Tc --99m αV-β3 IInttegrriin • Pre -operative staging to exclude multifocal/contralateral Tc --99m Annexiin V cancers Tc --99m Gllucarratte • Neo -adjuvant chemotherapy evaluation Tc --99m EC --gllucosamiine Tc --99m ((V)) --DMSA Tc --99m Viittamiin B12 Alternative radiotracers I-I-123 IIodo --esttrradiioll I-I-123 Metthoxy --viinyllesttrradiioll • Improved detection of lesions < 5 mm I-I-123 Diimetthyll --Tamoxiiffen • Improved detection of DCIS and atypia I-I-123 IIodo --metthoxybenzamiide
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