Aim:Several cationic radiotracers originally developed as myocardial perfusion agents have shown potential for both early detection of cancer and non-invasive monitoring of multiple drug resistance(MDR)by single photo...Aim:Several cationic radiotracers originally developed as myocardial perfusion agents have shown potential for both early detection of cancer and non-invasive monitoring of multiple drug resistance(MDR)by single photon emission computed tomography.We have introduced two cationic complexes,^(99m)Tc-DMEOP[di-methoxy-tris-pyrazolyl-^(99m)Tc-(CO)_(3)]and ^(99m)Tc-TMEOP[tri-methoxy-tris-pyrazolyl-^(99m)Tc-(CO)_(3)],which showed excellent preclinical results as cardiac imaging probes,namely a persistent heart uptake with rapid blood and liver clearance.This study aimed at the evaluation of their usefulness for tumoral detection and functional assessment of MDR.Methods:The uptake and efflux kinetics of ^(99m)Tc-DMEOP and ^(99m)Tc-TMEOP were evaluated in human prostate,lung,and breast cancer cell lines,including drug-resistant cell lines that are known to overexpress the MDR P-glycoprotein(Pgp).The effects of MDR modulators were also studied.In vivo studies were performed in xenografted tumor models,and the MDR phenotype of the tumors was confirmed by Western blot.Results:The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for ^(99m)Tc-Sestamibi,increasing over time.The uptake of ^(99m)Tc-TMEOP is greatly reduced in cells overexpressing Pgp and increased in the presence of a Pgp modulator.In nude mice,the tumor uptake of ^(99m)Tc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp tumors.Conclusion:The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for ^(99m)Tc-Sestamibi,increasing over time.The uptake of ^(99m)Tc-TMEOP is greatly reduced in cells overexpressing Pgp,and increased in the presence of a Pgp modulator.In nude mice,the tumor uptake of ^(99m)Tc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp tumors.展开更多
基金This work was supported by Covidien(Petten,The Netherlands).
文摘Aim:Several cationic radiotracers originally developed as myocardial perfusion agents have shown potential for both early detection of cancer and non-invasive monitoring of multiple drug resistance(MDR)by single photon emission computed tomography.We have introduced two cationic complexes,^(99m)Tc-DMEOP[di-methoxy-tris-pyrazolyl-^(99m)Tc-(CO)_(3)]and ^(99m)Tc-TMEOP[tri-methoxy-tris-pyrazolyl-^(99m)Tc-(CO)_(3)],which showed excellent preclinical results as cardiac imaging probes,namely a persistent heart uptake with rapid blood and liver clearance.This study aimed at the evaluation of their usefulness for tumoral detection and functional assessment of MDR.Methods:The uptake and efflux kinetics of ^(99m)Tc-DMEOP and ^(99m)Tc-TMEOP were evaluated in human prostate,lung,and breast cancer cell lines,including drug-resistant cell lines that are known to overexpress the MDR P-glycoprotein(Pgp).The effects of MDR modulators were also studied.In vivo studies were performed in xenografted tumor models,and the MDR phenotype of the tumors was confirmed by Western blot.Results:The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for ^(99m)Tc-Sestamibi,increasing over time.The uptake of ^(99m)Tc-TMEOP is greatly reduced in cells overexpressing Pgp and increased in the presence of a Pgp modulator.In nude mice,the tumor uptake of ^(99m)Tc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp tumors.Conclusion:The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for ^(99m)Tc-Sestamibi,increasing over time.The uptake of ^(99m)Tc-TMEOP is greatly reduced in cells overexpressing Pgp,and increased in the presence of a Pgp modulator.In nude mice,the tumor uptake of ^(99m)Tc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp tumors.
