PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the Visualization of beta-Amyloid Plaques

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F13%3A10139591" target="_blank" >RIV/00216208:11310/13:10139591 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1021/ml400042w" target="_blank" >http://dx.doi.org/10.1021/ml400042w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/ml400042w" target="_blank" >10.1021/ml400042w</a>

Jazyk výsledku

angličtina

Název v původním jazyce

PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the Visualization of beta-Amyloid Plaques

Popis výsledku v původním jazyce

In an effort toward the visualization of beta-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a well-established marker of Afi plaques, to DO3A-monoamide that is capable of forming stable, noncharged complexes with different trivalent metal ions including Gd3+ for MRI and In-111(3+). for SPECT applications. Proton relaxivity measurements evidenced binding of Gd(DO3A-PiB) to the amyloid peptide A beta(1-40) and to human serum albumin, resulting in a two- and four-fold relaidvity increase, respectively. Ex vivo immunohistochemical studies showed that the DO3A-PiB complexes selectively target A beta plaques on Alzheimer's disease human brain tissue. Ex vivo biodistribution dataobtained for the In-111-analogue pointed to a moderate blood-brain barrier (BBB) penetration in adult male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min postinjection.

Název v anglickém jazyce

PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the Visualization of beta-Amyloid Plaques

Popis výsledku anglicky

In an effort toward the visualization of beta-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a well-established marker of Afi plaques, to DO3A-monoamide that is capable of forming stable, noncharged complexes with different trivalent metal ions including Gd3+ for MRI and In-111(3+). for SPECT applications. Proton relaxivity measurements evidenced binding of Gd(DO3A-PiB) to the amyloid peptide A beta(1-40) and to human serum albumin, resulting in a two- and four-fold relaidvity increase, respectively. Ex vivo immunohistochemical studies showed that the DO3A-PiB complexes selectively target A beta plaques on Alzheimer's disease human brain tissue. Ex vivo biodistribution dataobtained for the In-111-analogue pointed to a moderate blood-brain barrier (BBB) penetration in adult male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min postinjection.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Medicinal Chemistry Letters

ISSN

1948-5875

e-ISSN

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Svazek periodika

4

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

5

Strana od-do

436-440

Kód UT WoS článku

000318892800005

EID výsledku v databázi Scopus

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