Imaging Multidrug Resistance in Hematological Malignancies.

Area of Science:

• Nuclear Medicine
• Oncology
• Pharmacology

Background:

• Multidrug resistance (MDR) in hematological malignancies is linked to drug efflux pumps: P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP), and lung resistance protein (LRP).
• Current detection methods for these proteins have variable results and may not reflect in vivo function.
• There is a need for reliable methods to assess MDR and guide treatment decisions.

Purpose of the Study:

• To evaluate the potential of nuclear medicine imaging techniques, specifically SPECT and PET, for non-invasively assessing drug efflux pump function in tumors.
• To explore the utility of radiolabeled compounds as substrates for Pgp and MRP in visualizing MDR.

Main Methods:

• Evaluation of Single-Photon Emission Tomography (SPECT) and Positron Emission Tomography (PET) for assessing Pgp- and MRP-mediated transport.
• Utilizing Tc-99m-labeled agents (e.g., Tc-99m-Sestamibi, Tc-99m-Tetrofosmin) as substrates for Pgp and MRP.
• Employing carbon-11-labeled radiopharmaceuticals (e.g., colchicine, verapamil, daunorubicin) with PET for in vivo assessment of Pgp function.

Main Results:

• SPECT and PET imaging show potential for non-invasively determining the function of Pgp and MRP.
• Tc-99m-Sestamibi, Tc-99m-Tetrofosmin, and various C-11 labeled compounds are recognized as substrates by these drug efflux pumps.
• These imaging modalities can visualize Pgp expression and Pgp-mediated transport functions in vivo.

Conclusions:

• Nuclear medicine imaging with SPECT and PET offers a promising approach to detect MDR in tumors.
• These techniques can assess the in vivo function of key drug efflux pumps (Pgp, MRP).
• This capability could aid in predicting or monitoring response to chemotherapy by identifying MDR prior to or after treatment.