Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
IBOX(2-(4 '-dimethylaminophenyl)-6-iodobenzoxazole): a ligand for imaging amyloid plaques in the brain
Autore:
Zhuang, ZP; Kung, MP; Hou, C; Plossl, K; Skovronsky, D; Gur, TL; Trojanowski, JQ; Lee, VMY; Kung, HF;
Indirizzi:
Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA Univ Penn PhiladelphiaPA USA 19104 pt Radiol, Philadelphia, PA 19104 USA Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 & Lab Med, Philadelphia, PA 19104 USA Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Pharmacol, Philadelphia, PA 19104 USA
Titolo Testata:
NUCLEAR MEDICINE AND BIOLOGY
fascicolo: 8, volume: 28, anno: 2001,
pagine: 887 - 894
SICI:
0969-8051(200111)28:8<887:I'ALFI>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALZHEIMERS-DISEASE; CONGO-RED; CHRYSAMINE-G; BINDING; COMPLEXES; PROTEIN; PROBES;
Keywords:
Alzheimer's disease; beta-amyloid; radioiodination and SPECT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Kung, HF Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 , Philadelphia, PA 19104 USA
Citazione:
Z.P. Zhuang et al., "IBOX(2-(4 '-dimethylaminophenyl)-6-iodobenzoxazole): a ligand for imaging amyloid plaques in the brain", NUCL MED BI, 28(8), 2001, pp. 887-894

Abstract

It is well known that overproduction and accumulation of beta -amyloid (A beta) plaques in the brain is a key event in the pathogenesis of Alzheimer's disease (AD). Previously it was demonstrated that [I-125]TZDM, 2-(4'-dimethylaminophenyl)-6-iodobenzothiazole, a thioflavin derivative, was an effective ligand with good in vitro and in vivo binding characteristics. To further improve the initial uptake and washout rate from the brain, important properties for in vivo imaging agents, a novel radioiodinated ligand, 2-(4'-dimethylaminophenyl)-6-iodobenzoxazole ([I-125]IBOX, 3), for detecting A beta plaques in the brain, was synthesized and evaluated. The new iodinated ligand, IBOX, is based on an isosteric replacement of a sulfur atom of TZDM by an oxygen, by which the molecular weight is reduced while the lipophilicity of the iodinated ligand is increased. Partition coefficients (P.C.) of these two ligands were 70 and 124 for TZDM and IBOX, respectively. In vitrobinding study indicated that the isosteric displacement yielded a new ligand with equal binding potency to A beta (1-40) aggregates (K-i = 1.9 and 0.8 nM for TZDM and IBOX, respectively). Autoradiography of postmortem brain sections of a confirmed AD patient by [I-125]IBOX showed excellent labelingof plaques similar to that observed with [I-125]TZDM. More importantly, invivo biodistribution of [I-125]IBOX in normal mice displayed superior peakbrain uptake (2.08% at 30 min vs 1.57% at 60 min dose/brain for [I-125]IBOX and [I-125]TZDM, respectively). In addition, the washout from the brain was much faster for [I-125]IBOX as compared to [I-125]TZDM. Based on the data presented for [I-125]IBOX, it is predicted that the brain trapping of this new radioiodinated ligand in the A beta containing regions will be more favorable than that of the parent compound, [I-125]TZDM. Further evaluation of [I-125]IBOX is warranted to confirm the A beta plaque labeling properties in vivo. (C) 2001 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/06/19 alle ore 17:10:19