Assessing p-glycoprotein (Pgp) activity in vivo utilizing 68Ga-Schiff base complexes

Area of Science:

• Radiochemistry
• Molecular Imaging
• Oncology

Background:

• P-glycoprotein (Pgp) is a key transporter in multidrug resistance (MDR).
• Non-invasive in vivo imaging of Pgp overexpression is crucial for MDR tumor identification.
• Current methods lack specificity for functional Pgp assessment.

Purpose of the Study:

• To synthesize and evaluate novel (68)Ga-labeled Schiff base compounds for imaging Pgp activity.
• To assess the in vitro and in vivo performance of these tracers in Pgp-positive tumor models.
• To determine the potential of these tracers for non-invasive detection of MDR tumors.

Main Methods:

• Six Schiff base compounds were synthesized and labeled with (68)Ga.
• In vitro studies involved Pgp-positive tumor cells and verapamil inhibition.
• In vivo studies utilized micro-PET imaging in tumor-bearing rats.

Main Results:

• High labeling yields (>92%) were achieved for most (68)Ga tracers.
• Tracers demonstrated varying cellular accumulation in vitro.
• In vivo studies identified (68)Ga-ENBDMPI and (68)Ga-MFL6.MZ for specific tumor uptake.
• Verapamil administration increased tracer concentration by ~25%, confirming Pgp activity.

Conclusions:

• Two (68)Ga-labeled ligands show promise for non-invasive imaging of intratumoral Pgp activity.
• These tracers could enable pre-therapeutic identification of patients with MDR tumors.
• This facilitates personalized treatment strategies for cancer patients.