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PET-compatible endothelin receptor radioligands: synthesis and first in vitro and in vivo studies.

Abstract：

:The expression and function of endothelin (ET) receptors is abnormal in cardiovascular diseases, tumor progression, and tumor metastasis. In this study, we prepared two [(18)F]-fluorinated derivatives of the non-peptide ET(A) receptor antagonist PD 156707 and evaluated their ET receptor binding potencies. Ex vivo as well as in vivo biodistribution studies in mice were performed, as well as the metabolism of the radiotracer, which was examined by metabolite analysis in mice and rats. All tested derivatives of PD 156707 exhibited potent in vitro pharmacological characteristics with K(i) values comparable to that of the lead compound. The biodistribution studies showed a high accumulation of the tracer in bile and intestine. In vivo we were able to show that the visualization of the heart as a major target organ with high ET(A)R expression is possible.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Höltke C,Law MP,Wagner S,Kopka K,Faust A,Breyholz HJ,Schober O,Bremer C,Riemann B,Schäfers M

doi

10.1016/j.bmc.2009.08.058

subject

Has Abstract

pub_date

2009-10-15 00:00:00

pages

7197-208

issue

20

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(09)00833-5

journal_volume

17

pub_type

杂志文章

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