Advances and Future Directions in Molecular Breast Imaging
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Advances and Future Directions in Molecular Breast Imaging
Juliana Sitta, MD Sirinivas Saripalli, MD Vani Vijayakumar, MD The authors have no disclosures.
Breast Cancer Facts
Top 10 Cancers by Rates of Cancer Deaths
All Types of Cancer, United States, 2018
+250,000
New cases of breast cancer each year
+42,000
Female breast cancer deaths each year
28%
5-year survival rate for metastatic BC
Rate per 100,000 people
U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on 2020 submission data (1999-2018): U.S. Department of Health and Human Services,
Centers for Disease Control and Prevention and National Cancer Institute; www.cdc.gov/cancer/dataviz, released in June 2021.
What is Molecular Breast Imaging?
Conventional systems Breast-specific
Scintimammography gamma imaging
NM Breast-dedicated Modalities
CZT-based
PEM/PET
gamma camera
Molecular Breast Imaging
Protocol Indications
Patient preparation: • Preoperative Staging in Newly Diagnosed
• Follicular phase of the menstrual cycle preferred, Breast Cancer
between days 2 and 12
• Fast for 3 hours prior to the study • Evaluation of Response to Neoadjuvant
• Warming blanket on arrival Chemotherapy
• Detection of Local Breast Cancer
Exam protocol: Recurrence
• 6–8 mCi (222–296 MBq) of 99mTc-sestamibi
intravenously • Breast Cancer Screening
• Light breast compression (about 5 lbs [2.3 kg])
• 7 minutes per view, total of 28 minutes • MBI as Adjunct to Conventional Breast
• Eight images in the craniocaudal (CC) and mediolateral Imaging for Problem Solving in
oblique (MLO) views Indeterminate Cases
Background uptake
Molecular Breast Imaging
Findings and Reporting
Reference to screening mammogram
Background uptake intensity
• Mild, moderate, severe
Lesion Uptake intensity Hruska, C.B., et al. Breast Cancer Res 20, 46 (2018).
• Compared to subcutaneous fat
• Mild, moderate, severe
Mass uptake
Nonmass uptake
• Distribution
• Symmetry
Associated findings
• Nipple, axilla, vessel uptake Conners AL, et al.
AJR Am J
Roentgenol. 2012.
Mass like uptake Non mass like uptake
Molecular Breast Imaging
Summary
Advantages Limitations
• Well-tolerated by patients • Requires injection
• Increased breast cancer detection rate in women • Long scanning time
with dense breast tissue
• May need cross-over expertise in nuclear medicine
• Safe radiation level and breast imaging
• Inexpensive
• Guided tissue biopsy available for suspicious Future
lesions identified on MBI
• Providing prognostic information
• TheranosticsWhat is PEM/dedicated breast PET? Whole body PET CT limitations in breast cancer: • Limited assessment of primary lesions • Low nuclear grade • Invasive lobular carcinoma • Ductal carcinoma in situ • Small tumors (
PEM/dedicated breast PET
Indications
• Currently, no ACR or SNMI clinical practice parameters
Initial staging
PEM vs MRI:
Berg et al. N=388:
• PEM comparable sensitivity, greater specificity, and similar additional disease detection Patient with biopsy proven invasive mammary carcinoma
(51% for PEM and 60% for MRI) in which MRI failed to demonstrate index lesion. On
Schilling et al. N=208: PEM the focal uptake corresponding to the lesion is
• PEM and MRI comparable sensitivity and specificity demonstrated.
Schilling K et al. Eur J Nucl Med Mol Imaging. 2011.
Monitoring response to neoadjuvant
chemotherapy
• Identify non responders, surgical planning
• Distinguishing recurrent carcinoma from scar
Monitoring response to neoadjuvant chemotherapy in
different breast cancer subtypes.
Soldevilla-Gallardo I et al. Am J Nucl Med Mol
Imaging. 2018; 8(5): 341–350.F18 estradiol Whole Body PET-CT
Indications
• Critical role in tumor heterogeneity
• Defining etiology of endocrine resistance
• Problem-solving
• Staging or restaging low metabolic rate breast cancer
Interfering medications
• ER modulator
• ER down regulator-may reduce detection of ER+
Protocol Improved depiction of low metabolic breast tumor subtypes. Ulaner et al:
• 3-6 mCi FES injection Comparison between F18 estradiol and F18 FDG for lobular carcinoma
• 45-60 min uptake time showing improved depiction of metastatic disease with F18 estradiol.
• Injection away from site of known primary breast cancer
Possible benefit of combined FDG and F18 estradiol (FES):
• Include all known lesions in the FOV
Bottoni et al:
• Single assessment could not predict overall disease-free survival
Limitations • Only FDG correlated with progression free survival (lower
• High liver uptake interfere with hepatic metastases assessment receptor expression, higher metabolic rate = lower degree of
• Bowel excretion cellular differentiation
• Less brain uptake • FES/FDG ratio correlated with overall survival
D’Huyvetter M et al. Journal of Nuclear Medicine August 2021Radioimmunotherapy
• Isotopes conjugated to mAb
• Target cancerous cells
Principles • Protect healthy cells
• Minimally invasive
• Short treatment
Adapted from BioRender.com
D’Huyvetter M et al. 2021:
Phase 1 clinical trial of 131I-GMIB-anti-HER2-VHH1
• Safe and stable after administration, with rapid
clearance in healthy volunteers
• Tracer accumulated in metastatic sites of patients
with stage IV HER2-positive breast cancer
• Patients who have progressed on trastuzumab,
pertuzumab, or trastuzumab emtansine, given its
different mode of action
D’Huyvetter M et al. Journal of Nuclear Medicine August 2021AI in Molecular Breast Imaging –
Classifying BPU
• Artificial intelligence based techniques such as machine learning
and convolutional neural networks, have made headway into
different subtypes of breast imaging, most notably in
mammography, and CT.
• The applications to molecular breast imaging are relatively
understudied but show great promise.
• One study completed in 2021 showed that CNN’s could be applied
to automatically and accurately characterize the background
parenchymal uptake (BPU) of breast tissue, an independent marker
for malignancy risk. This correlates with tissue density seen on
mammograph
• This objectivizes BPU to minimize inter-observer and intra-observer
variability. It also provides objective characterization of BPU in
patients undergoing tamoxifen or aromatase inhibitors.
• Further investigations will look into how marked BPU uptake differs
from radiotracer uptake as in a tumor.
Carter RE, Attia ZI, Geske JR, Conners AL, Whaley DH, Hunt KN, O'Connor MK, Rhodes DJ, Hruska CB. Classification of Background Parenchymal Uptake on Molecular Breast Imaging
Using a Convolutional Neural Network. JCO Clin Cancer Inform. 2019 Feb;3:1-11. doi: 10.1200/CCI.18.00133. PMID: 30807208; PMCID: PMC6446086.
D’Huyvetter M et al. Journal of Nuclear Medicine August 2021Radiomics based on 18F-FDG PET/CT to
differentiate breast carcinoma from
lymphoma
• In one study published in 2021, standardized uptake values
were combined with radiomic features obtained from 18F-
FDG PET/CT to accurately classify breast tumors into
carcinoma or lymphoma.
• When combined with clinical information, the model was
able to accurately characterize with AUC of 0.867 and 0.806. As an example of the findings in this paper, a radiomics-based model was able
to differentiate between (A) breast lymphoma and (B) breast carcinoma
which otherwise appear indistinguishable based on traditional features on CT
and PET/CT.
Ou X, Zhang J, Wang J, et al. Radiomics based on 18 F‐FDG PET/CT could differentiate breast carcinoma from breast lymphoma using machine‐learning approach: A preliminary study. Cancer
Medicine. 2019;9(2):496-506. doi:10.1002/cam4.2711
D’Huyvetter M et al. Journal of Nuclear Medicine August 2021Summary • Breast dedicated molecular imaging provides safe, inexpensive breast cancer detection rate in women with dense breast tissue • Guided tissue biopsy available or under development for suspicious lesions identified on MBI, PEM, and db-PET systems • Breast dedicated modalities may require cross over expertise or nuclear medicine and breast imager radiologists • Continued research looking at noninvasive prognostic tools that are well-tolerated by patients and account for tumor heterogeneity • Great potential of radionuclides and radiopharmaceuticals for breast cancer treatment with promising alternative for HER2 positive patients with progression after trastuzumab treatment
References
• Polan RL, Klein BD, Richman RH. Scintimammography in patients with minimal mammographic or clinical findings. Radiographics. 2001 May-Jun;21(3):641-53; discussion 653-5. doi:
10.1148/radiographics.21.3.g01ma26641. PMID: 11353112.
• MacDonald L, Edwards J, Lewellen T, Haseley D, Rogers J, Kinahan P. Clinical imaging characteristics of the positron emission mammography camera: PEM Flex Solo II. J Nucl Med. 2009 Oct;50(10):1666-75.
doi: 10.2967/jnumed.109.064345. Epub 2009 Sep 16. PMID: 19759118; PMCID: PMC2873041.
• Hunt KN, Conners AL, Goetz MP, O'Connor MK, Suman V, Kalari K, Weinshilboum R, Wang L, Carter J, McLaughlin S, Aspitia AM, Gray R, Northfelt D, Boughey JC. Comparison of 99mTc-Sestamibi Molecular
Breast Imaging and Breast MRI in Patients With Invasive Breast Cancer Receiving Neoadjuvant Chemotherapy. AJR Am J Roentgenol. 2019 Oct;213(4):932-943. doi: 10.2214/AJR.18.20628. Epub 2019 Jun 5.
PMID: 31166752.
• Kim S, Plemmons J, Hoang K, Chaudhuri D, Kelley A, Cunningham T, Hoefer R. Breast-Specific Gamma Imaging Versus MRI: Comparing the Diagnostic Performance in Assessing Treatment Response After
Neoadjuvant Chemotherapy in Patients With Breast Cancer. AJR Am J Roentgenol. 2019 Mar;212(3):696-705. doi: 10.2214/AJR.17.18930. Epub 2019 Jan 8. PMID: 30620672.
• Brem RF, Ruda RC, Yang JL, Coffey CM, Rapelyea JA. Breast-Specific γ-Imaging for the Detection of Mammographically Occult Breast Cancer in Women at Increased Risk. J Nucl Med. 2016 May;57(5):678-84.
doi: 10.2967/jnumed.115.168385. Epub 2016 Jan 28. PMID: 26823569.
• Shermis RB, Wilson KD, Doyle MT, Martin TS, Merryman D, Kudrolli H, Brenner RJ. Supplemental Breast Cancer Screening With Molecular Breast Imaging for Women With Dense Breast Tissue. AJR Am J
Roentgenol. 2016 Aug;207(2):450-7. doi: 10.2214/AJR.15.15924. Epub 2016 May 17. PMID: 27186635.
• Shermis RB, Redfern RE, Burns J, Kudrolli H. Molecular Breast Imaging in Breast Cancer Screening and Problem Solving. Radiographics. 2017 Sep-Oct;37(5):1309-1606. doi: 10.1148/rg.2017160204. PMID:
28898193.
• Cędrowska E, Pruszyński M, Gawęda W, Żuk M, Krysiński P, Bruchertseifer F, Morgenstern A, Karageorgou MA, Bouziotis P, Bilewicz A. Trastuzumab Conjugated Superparamagnetic Iron Oxide Nanoparticles
Labeled with 225Ac as a Perspective Tool for Combined α-Radioimmunotherapy and Magnetic Hyperthermia of HER2-Positive Breast Cancer. Molecules. 2020 Feb 25;25(5):1025. doi:
10.3390/molecules25051025. PMID: 32106568; PMCID: PMC7179151.
• Puttemans J, Dekempeneer Y, Eersels JL, et al. Preclinical targeted α- and β−-radionuclide therapy in HER2-positive brain metastasis using
camelid single-domain antibodies. Cancers (Basel). 2020;12:1017. Thank you!
• Altıparmak Güleç B, Yurt F. Treatment with Radiopharmaceuticals and Radionuclides in Breast Cancer: Current Options. Eur J Breast Health.
2021 Jun 24;17(3):214-219. doi: 10.4274/ejbh.galenos.2021.2021-3-4. PMID: 34263148; PMCID: PMC8246056.
• Razumienko EJ, Chen JC, Cai Z, Chan C, Reilly RM. Dual-Receptor-Targeted Radioimmunotherapy of Human Breast Cancer Xenografts in
Athymic Mice Coexpressing HER2 and EGFR Using 177Lu- or 111In-Labeled Bispecific Radioimmunoconjugates. J Nucl Med. 2016
Mar;57(3):444-52. doi: 10.2967/jnumed.115.162339. Epub 2015 Oct 1. PMID: 26429962.
• Ulaner GA, Jhaveri K, Chandarlapaty S, Hatzoglou V, Riedl CC, Lewis JS, Mauguen A. Head-to-Head Evaluation of 18F-FES and 18F-FDG PET/CT
in Metastatic Invasive Lobular Breast Cancer. J Nucl Med. 2021 Mar;62(3):326-331. doi: 10.2967/jnumed.120.247882. Epub 2020 Jul 17.
PMID: 32680923; PMCID: PMC8049349.
• Bottoni G, Piccardo A, Fiz F, Siri G, Matteucci F, Rocca A, Nanni O, Monti M, Brain E, Alberini JL, Dib B, Sacchetti GM, Saggia C, Rossi V, Harbeck
N, Wuerstlein R, Degenhardt T, DeCensi A, Rollandi GA, Gennari A. Heterogeneity of bone metastases as an important prognostic factor in Juliana Sitta, MD
patients affected by oestrogen receptor-positive breast cancer. The role of combined [18F]Fluoroestradiol PET/CT and
[18F]Fluorodeoxyglucose PET/CT. Eur J Radiol. 2021 Aug;141:109821. doi: 10.1016/j.ejrad.2021.109821. Epub 2021 Jun 10. PMID: 34139575. jsitta@umc.edu
D’Huyvetter M et al. Journal of Nuclear Medicine August 2021You can also read
