In Vivo Detection of Multidrug-Resistance Related Proteins in Locally Advanced Breast Cancer Using 99mTc-MIBI SPECT/CT Imaging: Correlation with Clinical Outcomes

Mostafa, Nadia M; Elnaggar, Maha S; Abdelhafez, Yasser G; Rezk, Khalid; Sherif, Mahmoud Farouk; Eltyb, Hanan A.; Ahmed, Shaimaa; Abu Elnga, Nagm Eldin; Hussien, Marwa T

doi:10.31557/APJCP.2024.25.9.3125

In Vivo Detection of Multidrug-Resistance Related Proteins in Locally Advanced Breast Cancer Using 99mTc-MIBI SPECT/CT Imaging: Correlation with Clinical Outcomes

Document Type : Research Articles

Authors

¹ Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Assiut University, Egypt.

² Department of Radiation Oncology and Nuclear Medicine, South Egypt cancer institute, Assuit University, Egypt.

³ Department of Radiology, University of California Davis, Sacramento, CA, U S A.

⁴ Department of Surgical Oncology, South Egypt cancer institute, Assuit University, Egypt.

⁵ Department of Pathology, Faculty of medicine, Assuit University, Egypt.

⁶ Department of Medical Oncology and Malignant Hematology, South Egypt cancer institute, Assuit University, Egypt.

⁷ General Surgery Department, Faculty of Medicine, Assiut University, Egypt.

⁸ Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Egypt.

10.31557/APJCP.2024.25.9.3125

Abstract

Objective: Neoadjuvant chemotherapy (NACT) is widely used for treating locally advanced Breast cancer (LABC). However, development of multidrug resistance (MDR) is the main underlying factor for chemoresistance. Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) is a substrate for MDR. This study aimed to analyze the relationship between expression of MDR-related proteins (P-gp and Bcl-2) and 99mTc-MIBI uptake and retention in BC tumor cells, pathologic response to NACT, disease free survival (DFS) and overall survival (OS). Methods: prospective analysis recruited 31 patients with LABC who received NACT between January 2019 and March 2020. 99mTc-MIBI planar and SPECT/CT imaging was conducted before and after NACT. Qualitative and quantitative analyses were performed, pre and post-NACT early and delayed lesion to non-lesion (LNL) ratios, and retention index (RI) of 99mTc-MIBI were calculated. Expression of P-gp and Bcl-2 in tumor cells was determined by immunohistochemistry. Results: Quantitively, inter-reader ICC for SPECT/CT based quantification was consistently higher than that of planar images. Post-NACT LNL ratios were significantly higher in patients with pathologic persistent disease (PPD). A change in RI between pre- and post-NACT scans demonstrated a significant association with DFS with a hazard ratio of 0.7 (95%CI: 06-1.0). Qualitatively, SPECT/CT was significantly more accurate compared to planar imaging in identifying residual viable tumor (81% compared to 57%). Her2neu positivity and high post-operative Bcl-2 and P-gp were associated with worse DFS. A significant association was found between increased expression of post-NACT Bcl-2 and PPD, advanced tumor stage and poor OS. Conclusion: 99mTc-MIBI SPECT/CT based qualitative evaluation of BC response to NACT is more accurate than planar imaging. Post-NACT MIBI retention is positively correlated with P-gp and Bcl-2 expression. 99mTc-MIBI SPECT/CT may predict MDR development. High post-NACT Bcl-2 expression is significantly associated with advanced tumor stage and OS. High post-NACT P-gp expression has a worse impact on pathologic response and DFS.

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