| Autor: |
Hendrikse, NH, Schinkel, AH, De Vries, EGE, Fluks, E, Van der Graaf, WTA, Willemsen, ATM, Vaalburg, W, Franssen, EJF |
| Přispěvatelé: |
Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Jazyk: |
angličtina |
| Rok vydání: |
1998 |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology, 124(7), 1413-1418. Wiley-Blackwell |
| ISSN: |
0007-1188 |
| Popis: |
1 Homozygously mdr1a gene disrupted mice (mdr1a(-/-) mice) and wild type mice (mdr1a(+/+) mice) were used to develop a method for P-glycoprotein (P-gp) function imaging non-invasively and to study the effect of a P-gp reversal agent on its function in vivo. 2 [C-11]verapamil (0.1 mg/kg) was administered and the changes in tissue concentrations were determined ex vivo by organ extirpation and in viva with PET. To block P-gp function, cyclosporin A was administered. 3 Biodistribution studies revealed 9.5-fold (P 4 Positron camera data showed lower [C-11]verapamil levels in the brain of mdr1a(+/+) mice compared to those in mdr1a(-/-) mice. [C-11]verapamil accumulation in the brain of mdr1a(+/+) mice was increased by cyclosporin A to levels comparable with those in mdr1a(-/-) mice, indicating that reversal of P-gp mediated efflux can be monitored by PET. 5 We conclude that cyclosporin A can fully block the P-gp function in the blood brain barrier and the testes and that PET enables the in viva measurement of P-gp function and reversal of its function noninvasively. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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