99mTc-MIBI SPECT/CT in Breast Malignancy

Tc-99m Sestamibi SPECT/CT for Prediction of the Response of Locally Advanced Breast Malignancy to Neoadjuvant Chemotherapy

99mTc-SestaMIBI mammoscintigraphy (MMS) may be used in patients with locally advanced breast cancer (LABC) scheduled for neoadjuvant chemotherapy. MMS may be performed for 1) nodal staging of axillary lymph node metastases, 2) prediction of chemosensitivity or Pgp/MDR-1 mediated chemoresistance, and 3) evaluation of efficacy to chemotherapy and radiation therapy.

MMS is routinely performed with planar/SPECT imaging according to the Society of Nuclear Medicine and European Association of Nuclear Medicine guidelines.

In this pilot study, an optimised acquisition protocol will be setup with SPECT/low-dose multislice CT in addition to planar imaging.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Device: SPECT/CT

Detailed Description

99mTc-SestaMIBI is a lipophylic cation as many cytotoxic chemotherapy drugs (i.e. anthracyclines, inhibitor of topoisomerase II, antimicrotubule, vinca alkaloids, inhibitors of DNA replication) accumulating in the mitochondria of tumour cells. MIBI tumour uptake is related to viability and proliferation due to increased perfusion and increased energy-dependent metabolism.

99mTc-SestaMIBI is a substrate for the glycoprotein P (Pgp) pump encoded by the multidrug resistance gene -1 (MDR-1). MIBI tumour uptake with no significant wash-out over time (<45% at 3H) predicts a chemosensitivity with no Pgp/MDR-1 overexpression. MIBI efflux with no significant tumour uptake predicts efflux of chemotherapy drugs from the tumour cells related to Pgp/MDR-1 overexpression or to anti-apoptotic Bcl-2 overexpression. Early MIBI efflux (< 1H) may also be related to pro-apoptotic Bax overexpression.

SPECT/CT will be used for anatomic localisation and and attenuation correction. CT from SPECT/CT is a low-dose (< 2 mSv) multislice CT (4 slice). SPECT/CT will also be used for correction of image-degrading factors including collimator-detector-response compensation for resolution recovery, and scatter correction. SPECT/CT based absolute semi-quantification of MIBI uptake into primary tumour and lymph nodes (i.e. standardised uptake value or SUV) will also be performed.

SPECT/CT optimised imaging will be compared to planar/SPECT conventional nuclear imaging for 1) detection of MIBI-avid primary breast tumour and lymph node metastases, 2) semi-quantification of MIBI uptake (T/B, SUV, and %wash-out) into primary breast tumour and lymph node metastases, 3) prediction of chemosensitivity at baseline, 3) Evaluation of chemotherapy efficacy after the first course of chemotherapy (after 2 weeks) compared to clinical response and histo-pathological response.

SPECT/CT mammoscintigraphy findings will be compared to clinical findings (palpation), radiological findings (mammography, US, MRI), and histo-pathological findings (Pgp/MDR-1 expression) into tumours after surgery.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • South Street Hospital - Department of Nuclear Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients with histologically proven breast cancer
• Patients with locally advanced breast cancer (stages T2-4 N0-3 M0)
• Patients scheduled for neoadjuvant chemotherapy
• Patients scheduled for radical modified mastectomy
• Patients with no physical and/or psychological contraindications
• Patients with no recent nuclear medicine study using long-lived isotopes (i.e. 67Ga, 111In, 131I) within the 48 hour preceding the mammoscintigraphy

Exclusion Criteria:

• Patient with no histologically proven breast cancer
• Patients with early stage T1 breast cancer
• Patients who are not candidates for neoadjuvant chemotherapy
• Patients who are not surgical candidates
• Patients with physical and/or psychological contraindications
• Pregnant or breast feeding patients
• Patients with a recent nuclear medicine study using long-lived isotopes (i.e. 67Ga, 111In, 131I) within the 48 hour preceding the mammoscintigraphy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Mammoscintigraphy with SPECT-CT optimized 99mTc-MIBI imaging (experimental arm) will be compared to conventional planar imaging. Mammoscintigraphy results before and after chemotherapy and radiation therapy, will be compared to the histopathological results after surgery.	Device: SPECT/CT; SPECT/Low-Dose MultiSclice CT; Other Names: Integrated SPECT/CT; Hybrid imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1- Nodal staging 2- Prediction of chemosensitivity 3- Evaluation of chemosensitivity	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Added-Value of integrated SPECT/Low-dose MultiSlice CT versus planar/SPECT imaging in mammoscintigraphy with 99mTc-SestaMIBI	1 year

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: University of Western Ontario, Canada
• Investigators: Principal Investigator: Irina Rachinsky, MD, MSc, The UWO - LHSC - Department of Nuclear Medicine; Study Chair: Albert A Driedger, MD, PhD, The UWO -LHSC - Department of Nuclear Medicine; Study Director: Muriel Brackstone, MD, The UWO - LHSC - Department of General Surgery; Study Director: Francisco Perera, MD, The UWO - LHSC - Department of Medical Oncology

Publications and helpful links

General Publications

• Moretti JL, Hauet N, Caglar M, Rebillard O, Burak Z. To use MIBI or not to use MIBI? That is the question when assessing tumour cells. Eur J Nucl Med Mol Imaging. 2005 Jul;32(7):836-42. doi: 10.1007/s00259-005-1840-x.
• Spanu A, Chessa F, Sanna D, Cottu P, Manca A, Nuvoli S, Madeddu G. Scintimammography with a high resolution dedicated breast camera in comparison with SPECT/CT in primary breast cancer detection. Q J Nucl Med Mol Imaging. 2009 Jun;53(3):271-80. Epub 2008 Jul 4.
• Maini CL, Tofani A, Sciuto R, Semprebene A, Cavaliere R, Mottolese M, Benevolo M, Ferranti F, Grandinetti ML, Vici P, Lopez M, Botti C. Technetium-99m-MIBI scintigraphy in the assessment of neoadjuvant chemotherapy in breast carcinoma. J Nucl Med. 1997 Oct;38(10):1546-51.
• Takamura Y, Miyoshi Y, Taguchi T, Noguchi S. Prediction of chemotherapeutic response by Technetium 99m--MIBI scintigraphy in breast carcinoma patients. Cancer. 2001 Jul 15;92(2):232-9. doi: 10.1002/1097-0142(20010715)92:23.0.co;2-g.
• Del Vecchio S, Zannetti A, Ciarmiello A, Aloj L, Caraco C, Fonti R, Botti G, D'Aiuto G, Salvatore M. Dynamic coupling of 99mTc-MIBI efflux and apoptotic pathway activation in untreated breast cancer patients. Eur J Nucl Med Mol Imaging. 2002 Jun;29(6):809-14. doi: 10.1007/s00259-002-0773-x. Epub 2002 Mar 13.
• Sciuto R, Pasqualoni R, Bergomi S, Petrilli G, Vici P, Belli F, Botti C, Mottolese M, Maini CL. Prognostic value of (99m)Tc-sestamibi washout in predicting response of locally advanced breast cancer to neoadjuvant chemotherapy. J Nucl Med. 2002 Jun;43(6):745-51.
• Khalkhali I, Diggles LE, Taillefer R, Vandestreek PR, Peller PJ, Abdel-Nabi HH. Procedure guideline for breast scintigraphy. Society of Nuclear Medicine. J Nucl Med. 1999 Jul;40(7):1233-5. No abstract available.
• Xu HB, Li L, Xu Q. Tc-99m sestamibi scintimammography for the diagnosis of breast cancer: meta-analysis and meta-regression. Nucl Med Commun. 2011 Nov;32(11):980-8. doi: 10.1097/MNM.0b013e32834b43a9.
• Schillaci O, Danieli R, Filippi L, Romano P, Cossu E, Manni C, Simonetti G. Scintimammography with a hybrid SPECT/CT imaging system. Anticancer Res. 2007 Jan-Feb;27(1B):557-62.
• Goldsmith SJ, Parsons W, Guiberteau MJ, Stern LH, Lanzkowsky L, Weigert J, Heston TF, Jones E, Buscombe J, Stabin MG; Society of Nuclear Medicine. SNM practice guideline for breast scintigraphy with breast-specific gamma-cameras 1.0. J Nucl Med Technol. 2010 Dec;38(4):219-24. doi: 10.2967/jnmt.110.082271. Epub 2010 Nov 5. No abstract available.
• Bombardieri E, Aktolun C, Baum RP, Bishof-Delaloye A, Buscombe J, Chatal JF, Maffioli L, Moncayo R, Mortelmans L, Reske SN. Breast scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging. 2003 Dec;30(12):BP107-14. doi: 10.1007/s00259-003-1354-3. No abstract available.

Helpful Links

• The University of Western Ontario

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: December 4, 2008
• First Submitted That Met QC Criteria: December 8, 2008
• First Posted (Estimate): December 9, 2008

Study Record Updates

• Last Update Posted (Estimate): March 5, 2012
• Last Update Submitted That Met QC Criteria: March 2, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Chemosensitivity; Integrated SPECT/CT; 99mTc-sestMIBI
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: R-08-383; 12967 (Other Identifier: REB)