99mTc-MIBI SPECT/CT in Breast Malignancy

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00804544
• Other study ID #: R-08-383
• Secondary ID: 12967
• Status: Terminated
• Phase: N/A
• First received: December 4, 2008
• Last updated: March 2, 2012
• Start date: September 2008
• Est. completion date: January 2010

Study information

• Verified date: March 2012
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 90 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer

Intervention

Device:
• SPECT/CT
SPECT/Low-Dose MultiSclice CT

Locations

Country	Name	City	State
Canada	South Street Hospital - Department of Nuclear Medicine	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Lawson Health Research Institute	University of Western Ontario, Canada

Country where clinical trial is conducted

Canada, 

References & Publications (11)

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. — View Citation

Del Vecchio S, Zannetti A, Ciarmiello A, Aloj L, Caracò 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. Epub 2002 Mar 13. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1- Nodal staging 2- Prediction of chemosensitivity 3- Evaluation of chemosensitivity		1 year	No
Secondary	Added-Value of integrated SPECT/Low-dose MultiSlice CT versus planar/SPECT imaging in mammoscintigraphy with 99mTc-SestaMIBI		1 year	No

External Links

•   Lawson Health Research Institute
•   The University of Western Ontario