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EJNMMI Research

, 3:10

First Online: 14 February 2013Received: 25 November 2012Accepted: 30 January 2013DOI: 10.1186-2191-219X-3-10

Cite this article as: Van Vlaslaer, A., Mortishire-Smith, R.J., Mackie, C. et al. EJNMMI Res 2013 3: 10. doi:10.1186-2191-219X-3-10

Abstract

BackgroundC-PiB has been developed as a positron-emission tomography PET ligand for evaluating fibrillar β-amyloid Aβ in the human brain. The ligand is rapidly metabolized, with approximately 10% of intact tracer remaining 30 min after injection. When C-PiB is used as a treatment endpoint in intervention studies for Alzheimer’s disease AD, a concern is whether the clearance of the tracer changes from one scan to the next, increasing within subject variability in the PET signal. Subjects enrolled in AD trials may start or stop medications that inhibit or induce xenobiotic metabolizing enzymes such as the cytochrome P450 CYP isozymes.

FindingsWe conducted CYP phenotyping in recombinantly expressed systems, and in human liver microsomes, to evaluate CYP isozyme contributions to the metabolism of PiB carrier and profiled microsomal and hepatocyte incubations for metabolites. The metabolism of PiB appears to be polyzymic, with direct conjugation via UDP-glucuronosyltransferases UGTs also occurring.

ConclusionIt is unlikely that CYP inhibition or induction will significantly influence the clearance of C-PiB.

KeywordsAmyloid Pittsburgh compound B Drug metabolism Hepatic clearance P450 phenotyping Electronic supplementary materialThe online version of this article doi:10.1186-2191-219X-3-10 contains supplementary material, which is available to authorized users.

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Autor: Anne Van Vlaslaer - Russell J Mortishire-Smith - Claire Mackie - Xavier Langlois - Mark E Schmidt

Fuente: https://link.springer.com/



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