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Imaging multidrug resistance P-glycoprotein transport function using microPET with technetium-94m-sestamibi
Heather M Bigott1, Julie L Prior, David R Piwnica-Worms
1Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, MO 63110, USA.
Molecular Imaging
|June 22, 2005
Summary
New PET imaging tracer (94m)Tc-MIBI effectively detects P-glycoprotein (Pgp) function, a key mechanism in multidrug resistance (MDR) in cancer. This tracer shows promise for visualizing MDR in patients.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Multidrug resistance (MDR) in cancer often involves the MDR1 efflux transporter P-glycoprotein (Pgp).
- Detecting Pgp function is crucial for understanding and overcoming treatment resistance.
- Radiotracers are valuable tools for in vivo molecular imaging.
Purpose of the Study:
- To synthesize and validate the positron-emitting radiotracer (94m)Tc-MIBI as a substrate for MDR1 Pgp.
- To assess the utility of (94m)Tc-MIBI for in vivo imaging of Pgp function using PET.
- To evaluate the impact of Pgp modulators on (94m)Tc-MIBI biodistribution.
Main Methods:
- Synthesis and cell transport studies of (94m)Tc-MIBI.
- Small-scale PET imaging and biodistribution studies in mdr1a/1b gene-deleted and wild-type mice.
- Tissue distribution studies in tumor-bearing nude mice (KB 3-1 and KB 8-5) with and without Pgp modulators.
Main Results:
- (94m)Tc-MIBI was successfully synthesized and confirmed as an MDR1 Pgp substrate in cell transport assays.
- In vivo PET imaging and biodistribution studies demonstrated (94m)Tc-MIBI's ability to detect Pgp function in mice.
- Tissue distribution studies showed the reversal effect of a Pgp modulator, confirming tracer responsiveness to Pgp activity.
- (94m)Tc-MIBI exhibited performance comparable to the established (99m)Tc-MIBI.
Conclusions:
- (94m)Tc-MIBI is biologically validated as a suitable radiotracer for PET imaging of Pgp-mediated multidrug resistance.
- This tracer holds potential for non-invasive assessment of Pgp function in cancer patients.
- The findings support the use of (94m)Tc-MIBI in preclinical research and potential clinical translation for MDR detection.