Visualization of multidrug resistance in vivo

被引:154
作者
Hendrikse, NH
Franssen, EJ
van der Graaf, WTA
Vaalburg, W
de Vries, EGE
机构
[1] Univ Groningen Hosp, PET Ctr, NL-9700 RB Groningen, Netherlands
[2] Univ Groningen Hosp, Dept Internal Med, Div Med Oncol, NL-9713 EZ Groningen, Netherlands
[3] Univ Groningen Hosp, Dept Nucl Med, NL-9713 EZ Groningen, Netherlands
关键词
multidrug resistance; single-photon emission tomography; positron emission tomography; P-glycoprotein; multidrug resistance-associated protein;
D O I
10.1007/s002590050390
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Various mechanisms are involved in multidrug resistance (MDR) for chemotherapeutic drugs, such as the drug efflux pumps, P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP). In this review the mechanisms involved in MDR are described and results are reviewed with particular attention to the in vivo imaging of Pgp and MRP. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However, these methods do not yield information about the dynamic function of Pgp and MRP in vivo. For the study of Pgp- and MRP-mediared transport, single-photon emission tomography (SPET) and positron emission tomography (PET) are available. Technetium-99m sestamibi is a substrate for Pgp and MRP, and has been used in clinical studies for tumour imaging, and to visualize blockade of Pgp-mediated transport after modulation of the Pgp pump. Other Tc-99m radiopharmaceuticals, such as Tc-99m-tetrofosmin and several Tc-99-Q complexes, are also substrates for Ppp, but to date only results from in vitro and animal studies are available for these compounds. Several agents, including [C-11]colchicine, [C-11]verapamil and [C-11]daunorubicin, have been evaluated for the quantification of Pgp-mediated transport with PET in vivo. The results suggest that radiolabelled colchicine, verapamil and daunorubicin are feasible substrates with which to image Pgp function in tumours. Uptake of [C-11]colchicine and [C-11]verapamil is relatively high in the chest area, reducing the value of both tracers for monitoring Pgp-mediated drug transport in rumours located in this region. In addition, it has to be borne in mind that only comparison of Pgp-mediated transport of radioalabelled substrates in the absence and in the presence of Pgp blockade gives quantitative information on Pgp-mediated pharmacokinetics, Leukotrienes are specific substrates for MRP. Therefore, N-[C-11]acetyl-leukotriene E-4 provides an opportunity to study MRP function non-invasively. Results obtained in MRP2 mutated GY/TR rats have demonstrated visualization of MRP-mediated transport. This tracer permits the study of MRP transport function abnormalities in vivo, e.g, in Dubin-Johnson patients, who are MRP2, gene deficient. Results obtained show the feasibility of using SPET and PET to study the functionality of MDR transporters in vivo.
引用
收藏
页码:283 / 293
页数:11
相关论文
共 92 条
[1]   THE MULTIDRUG RESISTANCE (MDR1) GENE-PRODUCT FUNCTIONS AS AN ATP CHANNEL [J].
ABRAHAM, EH ;
PRAT, AG ;
GERWECK, L ;
SENEVERATNE, T ;
ARCECI, RJ ;
KRAMER, R ;
GUIDOTTI, G ;
CANTIELLO, HF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (01) :312-316
[2]  
ALMQUIST KC, 1995, CANCER RES, V55, P102
[3]  
BAILLY JD, 1995, LEUKEMIA, V9, P799
[4]  
Ballinger J. R., 1995, Journal of Nuclear Medicine, V36, p202P
[5]  
Ballinger JR, 1996, J NUCL MED, V37, P1578
[6]   TC-99(M)-SESTAMIBI AS AN AGENT FOR IMAGING P-GLYCOPROTEIN-MEDIATED MULTIDRUG-RESISTANCE - IN-VITRO AND IN-VIVO STUDIES IN A RAT BREAST-TUMOR CELL-LINE AND ITS DOXORUBICIN-RESISTANT VARIANT [J].
BALLINGER, JR ;
HUA, HA ;
BERRY, BW ;
FIRBY, P ;
BOXEN, I .
NUCLEAR MEDICINE COMMUNICATIONS, 1995, 16 (04) :253-257
[7]  
Barbarics E, 1998, CANCER RES, V58, P276
[8]   TC-99M-HIDA CHOLESCINTIGRAPHY IN DUBIN-JOHNSON AND ROTOR SYNDROMES [J].
BARMEIR, S ;
BARON, J ;
SELIGSON, U ;
GOTTESFELD, F ;
LEVY, R ;
GILAT, T .
RADIOLOGY, 1982, 142 (03) :743-746
[9]  
BOURHIS J, 1989, CANCER RES, V49, P5062
[10]  
Buchler M, 1996, J BIOL CHEM, V271, P15091