Noninvasive monitoring of HPMA copolymer-RGDfK conjugates by magnetic resonance imaging.
Pharm Res
; 26(5): 1121-9, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19160028
ABSTRACT
PURPOSE:
To evaluate the tumor targeting potential of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-gadolinium(Gd)-RGDfK conjugates by magnetic resonance (MR) T1-mapping.METHODS:
HPMA copolymers with and without RGDfK were synthesized to incorporate side chains for Gd chelation. The conjugates were characterized by their side-chain contents and r(1) relaxivity. In vitro integrin-binding affinities of polymeric conjugates were assessed via competitive cell binding assays on HUVEC endothelial cells and MDA-MB-231 breast cancer cells. In vivo MR imaging was performed on MDA-MB-231 tumor-bearing SCID mice at different time points using non-targetable and targetable polymers. The specificity of alphavbeta3 targeting was assessed by using non-paramagnetic targetable polymer to block alphavbeta3 integrins followed by injection of paramagnetic targetable polymers after 2 h.RESULTS:
The polymer conjugates showed relaxivities higher than Gd-DOTA. Endothelial cell binding studies showed that IC(50) values for the copolymer with RGDfK binding to alphavbeta3 integrin-positive HUVEC and MDA-MB-231 cells were similar to that of free peptide. Significantly lower T1 values were observed at the tumor site after 2 h using targetable conjugate (p < 0.012). In vivo blocking study showed significantly higher T1 values (p < 0.045) compared to targetable conjugate.CONCLUSION:
These results demonstrate the potential of this conjugate as an effective targetable MR contrast agent for tumor imaging and therapy monitoring.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Peptídeos Cíclicos
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Neoplasias da Mama
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Imageamento por Ressonância Magnética
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Meios de Contraste
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Hempa
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2009
Tipo de documento:
Article