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Titolo:
Physicochemical and biological evaluation of P792, a rapid-clearance blood-pool agent for magnetic resonance imaging
Autore:
Port, M; Corot, C; Raynal, I; Idee, JM; Dencausse, A; Lancelot, E; Meyer, D; Bonnemain, B; Lautrou, J;
Indirizzi:
MRI Contrast Agent Res, Guerbet, F-95943 Roissy, France MRI Contrast AgentRes Roissy France F-95943 bet, F-95943 Roissy, France
Titolo Testata:
INVESTIGATIVE RADIOLOGY
fascicolo: 8, volume: 36, anno: 2001,
pagine: 445 - 454
SICI:
0020-9996(200108)36:8<445:PABEOP>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
MR CONTRAST AGENTS; GD-DTPA; ANGIOGRAPHY; COMPLEXES; ANGIOGENESIS; ALBUMIN; PHARMACOKINETICS; GD(III); RABBITS;
Keywords:
MRI blood-pool contrast agent; relaxivity; pharmacokinetics; biocompatibility; tolerance; clinical indications;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Port, M MRI Contrast Agent Res, Guerbet, BP 50400, F-95943 Roissy, France MRI Contrast Agent Res BP 50400 Roissy France F-95943 ssy, France
Citazione:
M. Port et al., "Physicochemical and biological evaluation of P792, a rapid-clearance blood-pool agent for magnetic resonance imaging", INV RADIOL, 36(8), 2001, pp. 445-454

Abstract

RATIONALE AND OBJECTIVES. To summarize the physicochemical characterization, pharmacokinetic behavior, and biological evaluation of P792, a new monogadolinated MRI blood-pool agent. METHODS. The molecular modeling of P792 was described The r(1) relaxivity properties of P792 were measured in water and 4% human serum albumin at different magnetic fields (20, 40, 60 MHz). The stability of the gadolinium complex was assessed. The pharmacokinetic and biodistribution profiles were studied in rabbits. Renal tolerance in dehydrated rats undergoing selective intrarenal injection was evaluated. Hemodynamic safety in rats and in vitrohistamine and leukotriene B-4 release were also tested. RESULTS. The mean diameter of P792 is 50.5 Angstrom and the r(1) relaxivity of this monogadolinium contrast agent is 29 L . mmol(-1) . . s(-1) at 60 MHz. The stability of the gadolinium complex in transmetallation is excellent. The pharmacokinetic and biodistribution profiles are consistent with that of a rapid-clearance blood-pool agent: P792 is mainly excreted by glomerular filtration, and its diffusion across normal endothelium is limited. Renal and hemodynamic safety is comparable to that of the nonspecific agent gadolinium-tetraazacyclododecane tetraacetic acid. No histamine or leukotriene B-4 release was found in RBL-2H3 isolated mastocytes. CONCLUSIONS. The relaxivity of P792 at clinical field is very high for a monogadolinium complex without protein binding. The pharmacokinetic and biodistribution profiles are consistent with those of a rapid-clearance blood-pool agent. Its initial safety profile is satisfactory. Experimental and clinical studies are underway to confirm the potential of P792 in MRI.

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Documento generato il 12/07/20 alle ore 03:25:13