Synthesis and Biological Evaluation of Rhein-Based MRI Contrast Agents for in Vivo Visualization of Necrosis.
Anal Chem
; 90(22): 13249-13256, 2018 11 20.
Article
em En
| MEDLINE
| ID: mdl-30379067
ABSTRACT
Early and accurate assessment of therapeutic response to anticancer therapy plays an important role in determining treatment planning and patient management in clinic. Magnetic rseonance imaging (MRI) of necrosis that occurs after cancer therapies provides chances for that. Here, we reported three novel MRI contrast agents, GdL1, GdL2, and GdL3, by conjugating rhein with gadolinium 2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]acetic acid (Gd-DOTA) through different linkers. The T1 relaxivities of three probes (7.28, 7.35, and 8.03 mM-1 s-1) were found to be higher than that of Gd-DOTA (4.28 mM-1 s-1). Necrosis avidity of GdL1 was evaluated on the rat models of reperfused liver infarction (RLI) by MRI, which showed an increase of T1-weighted contrast between necrotic and normal liver during 0.5-12 h. Besides, L1 was also labeled with 64Cu to assess its necrosis avidity on rat models of RLI and muscle necrosis (MN) by a γ-counter. The uptakes of 64CuL1 in necrotic liver and muscle were higher than those in normal liver and muscle ( P < 0.05). Then, the ability of GdL1 to assess therapeutic response was tested on rats bearing Walker 256 breast carcinoma injected with a vascular disrupting agent CA4P by MR imaging. The signal intensity of tumoral necrosis was strongly enhanced, and the contrast ratio between necrotic and viable tumor was 1.63 ± 0.11 at 3 h after administration of GdL1. Besides, exposed DNA in necrosis cells may be an important mechanism of three probes targeting to necrosis cells. In summary, GdL1 may serve as a promising MRI contrast agent for accurate assessment of treatment response.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Antraquinonas
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Meios de Contraste
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Compostos Heterocíclicos
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Necrose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Anal Chem
Ano de publicação:
2018
Tipo de documento:
Article