In vivo imaging of hepatobiliary transport function mediated by multidrug resistance associated protein and P-glycoprotein
| العنوان: | In vivo imaging of hepatobiliary transport function mediated by multidrug resistance associated protein and P-glycoprotein |
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| المؤلفون: | Elisabeth G.E. de Vries, Willem Vaalburg, Folkert Kuipers, Charles M. A. Bijleveld, Rick Havinga, N. Harry Hendrikse, Winette T. A. van der Graaf, Coby Meijer |
| المساهمون: | Center for Liver, Digestive and Metabolic Diseases (CLDM), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical pharmacology and pharmacy |
| المصدر: | Hendrikse, N H, Kuipers, F, Meijer, C, Havinga, R, Bijleveld, C M A, Van Der Graaf, W T A, Vaalburg, W & De Vries, E G E 2004, ' In vivo imaging of hepatobiliary transport function mediated by multidrug resistance associated protein and P-glycoprotein ', Cancer Chemotherapy and Pharmacology, vol. 54, no. 2, pp. 131-138 . https://doi.org/10.1007/s00280-004-0793-2 Cancer Chemotherapy and Pharmacology, 54(2), 131-138. SPRINGER Cancer Chemotherapy and Pharmacology, 54(2), 131-138. Springer Verlag |
| بيانات النشر: | Springer Science and Business Media LLC, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Male, Technetium Tc 99m Sestamibi, Cancer Research, MRP, ACUTE MYELOID-LEUKEMIA, Pharmacology, TC-99M-HIDA CHOLESCINTIGRAPHY, Toxicology, (99m)Technetium, CONJUGATE EXPORT PUMP, chemistry.chemical_compound, Dubin–Johnson syndrome, In vivo, medicine, Animals, Bile, Pharmacology (medical), Secretion, ATP Binding Cassette Transporter, Subfamily B, Member 1, Rats, Wistar, Radionuclide Imaging, functional imaging, P-glycoprotein, biology, GY/TR, Technetium, Technetium Tc 99m Lidofenin, Transporter, Glutathione, medicine.disease, GENE, ATP-DEPENDENT TRANSPORT, Rats, carbohydrates (lipids), Liver, Oncology, chemistry, Biochemistry, Cell culture, biology.protein, P-gp, DUBIN-JOHNSON-SYNDROME, Multidrug Resistance-Associated Proteins, Radiopharmaceuticals, Perfusion, CARCINOMA CELL-LINE, MEMBRANE-VESICLES |
| الوصف: | Multidrug resistance associated proteins (MRPs) and P-glycoprotein (P-gp) are involved in hepatobiliary transport of various compounds. Our aim was (1) to define transporter specificity of the cholescintigraphic agents 99mTc-HIDA and 99mTc-MIBI, which are used clinically for myocardial perfusion measurements; and (2) to deduce MRP and P-gp functions in vivo from hepatic 99mTc kinetics. Accumulation of radioactivity was measured in the human tumor cell lines GLC4, GLC4/ADR 150x (MRP1-overexpressing/ P-gp-negative) and GLC4/P-gp (P-gp-overexpressing). Bile secretion was quantified in untreated and in glutathione-depleted control and MRP2-deficient (GY/TR-) rats. Hepatobiliary transport was measured using a gamma camera in both types of rats. 99mTc-HIDA accumulated 5.8-fold less in GLC4/ADR 150x calls than in GLC4 or GLC4/P-gp cells. In GLC4/ADR150x, the cellular 99mTc-HIDA content was increased 3.4-fold by the MRP1,2 inhibitor MK571 (50 μM), while MK571 had no measurable effect in GLC4 and GLC4/P-gp cells. 99mTc-MIBI accumulated less in GLC4/P-gp and GLC 4/ ADR150x cells than in GLC4 cells. Bile secretion of 99mTc-HIDA was impaired in GY/TR- compared to control rats and not affected by glutathione depletion in GY/TR- rats. Hepatic secretion of 99mTc-HIDA was slower in GY/TR- (t1/2 40 min) than in control rats (t1/2 7 min). Bile secretion of 99mTc-MIBI was similar in both rat strains and impaired by glutathione depletion in control rats only, indicating compensatory activity of additional transporter(s) in GY/TRT- rats. 99mTc-HIDA is transported only by MRP1,2 only, while 99mTc-MIBI is transported by P-gp and MRP1,2. The results indicate that hepatic P-gp and MRP1,2 function can be assessed in vivo by sequential use of both radiopharmaceuticals. |
| تدمد: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-004-0793-2 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f7b04e202ad730df01a39a7e7e225a07 https://doi.org/10.1007/s00280-004-0793-2 |
| Rights: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....f7b04e202ad730df01a39a7e7e225a07 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320843 03445704 |
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| DOI: | 10.1007/s00280-004-0793-2 |