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Updated: Jul 13, 2026
Tracking the Mammary Architectural Features and Detecting Breast Cancer with Magnetic Resonance Diffusion Tensor Imaging
Published on: December 15, 2014
Functional imaging of multidrug resistance in breast cancer
Silvana Del Vecchio1, Antonella Zannetti, Barbara Salvatore
1Institute of Biostructures and Biomages of the National Research Council (CNR), Naples (Italy); Institute of Biostructures and Biomages of the National Research Council (CNR), Naples (Italy).
Abstract:
Intrinsic or acquired multidrug resistance is the major cause of treatment failure in many human cancers. Multiple cellular mechanisms may contribute to the development of multidrug resistance including overexpression of P-glycoprotein (Pgp). The use of 99mTc-labeled lipophilic cations, which are transport substrate of Pgp, raised the possibility to predict the tumor response to treatment and to identify patients who will become refractory to subsequent therapy. Among these agents, 99mTc-MIBI is the most widely evaluated tracer and may serve as a paradigm of this class of compounds. In particular, many studies have shown the prognostic value of 99mTc-MIBI scan in different types of malignancy including breast cancer and the correlation with the expression of Pgp. However, additional mechanisms of cell resistance, mainly involving alterations of apoptosis, may also affect 99mTc-MIBI uptake in tumors. In particular, overexpression of the anti-apoptotic protein Bcl-2 prevents tumor cells to enter apoptosis and inhibits tracer accumulation into mitochondria. Therefore, while an absent or reduced early tracer uptake in large breast carcinomas reflects the existence of a defective apoptotic program, an enhanced tracer clearance in 99mTc-MIBI positive lesions reflects the activity of drug transporters such as Pgp. The existence of two different mechanisms underlying the predictive role of 99mTc-MIBI scan may be important to establish whether individual patients may benefit from Pgp inhibitors or Bcl-2 antagonists.
Insights
99mTc-MIBI scans can predict cancer treatment response by assessing multidrug resistance mechanisms. This imaging technique evaluates both P-glycoprotein activity and apoptosis, aiding in personalized therapy selection.
Area of Science:
- Oncology
- Nuclear Medicine
- Molecular Biology
Background:
- Multidrug resistance (MDR) is a primary cause of cancer treatment failure.
- Overexpression of P-glycoprotein (Pgp) and altered apoptosis are key MDR mechanisms.
- 99mTc-labeled lipophilic cations, like 99mTc-MIBI, are Pgp substrates used in imaging.
Purpose of the Study:
- To evaluate the prognostic value of 99mTc-MIBI scans in predicting tumor response to therapy.
- To correlate 99mTc-MIBI uptake with Pgp expression and apoptosis-related proteins (e.g., Bcl-2).
- To explore the dual mechanisms (Pgp transport and apoptosis) influencing 99mTc-MIBI uptake.
Main Methods:
- Utilized 99mTc-MIBI scintigraphy in various malignancies, including breast cancer.
- Correlated imaging findings with Pgp expression levels.
- Investigated the role of anti-apoptotic proteins, such as Bcl-2, in modulating tracer uptake.
Main Results:
- 99mTc-MIBI uptake correlates with Pgp expression, indicating potential for Pgp inhibitor efficacy.
- Reduced early tracer uptake in tumors suggests defects in apoptosis.
- Enhanced tracer clearance in positive lesions points to active Pgp drug transporters.
Conclusions:
- 99mTc-MIBI scintigraphy offers prognostic information by reflecting MDR mechanisms.
- Absent/reduced uptake indicates defective apoptosis, while enhanced clearance suggests Pgp activity.
- Understanding these dual mechanisms can guide the selection of targeted therapies, such as Pgp or Bcl-2 inhibitors.
