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Development of purine-derived 18F-labeled pro-drug tracers for imaging of MRP1 activity with PET.

Abstract：

:Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter that has been implicated in the pathology of several neurological diseases and is associated with development of multidrug resistance. To enable measurement of MRP1 function in the living brain, a series of 6-halopurines decorated with fluorinated side chains have been synthesized and evaluated as putative pro-drug tracers. The tracers were designed to undergo conjugation with glutathione within the brain and hence form the corresponding MRP1 substrate tracers in situ. 6-Bromo-7-(2-[(18)F]fluoroethyl)purine showed good brain uptake and rapid metabolic conversion. Dynamic PET imaging demonstrated a marked difference in brain clearance rates between wild-type and mrp1 knockout mice, suggesting that the tracer can allow noninvasive assessment of MRP1 activity in vivo.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Galante E,Okamura T,Sander K,Kikuchi T,Okada M,Zhang MR,Robson M,Badar A,Lythgoe M,Koepp M,Årstad E

doi

10.1021/jm401764a

subject

Has Abstract

pub_date

2014-02-13 00:00:00

pages

1023-32

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

57

pub_type

杂志文章

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