Real-time, image-guided, convection-enhanced delivery of interleukin 13 bound to pseudomonas exotoxin.
Clin Cancer Res
; 12(10): 3145-51, 2006 May 15.
Article
em En
| MEDLINE
| ID: mdl-16707614
ABSTRACT
PURPOSE:
To determine if the tumor-targeted cytotoxin interleukin 13 bound to Pseudomonas exotoxin (IL13-PE) could be delivered to the brainstem safely at therapeutic doses while monitoring its distribution in real-time using a surrogate magnetic resonance imaging tracer, we used convection-enhanced delivery to perfuse rat and primate brainstems with IL13-PE and gadolinium-bound albumin (Gd-albumin). EXPERIMENTALDESIGN:
Thirty rats underwent convective brainstem perfusion of IL13-PE (0.25, 0.5, or 10 microg/mL) or vehicle. Twelve primates underwent convective brainstem perfusion of either IL13-PE (0.25, 0.5, or 10 microg/mL; n = 8), co-infusion of 125I-IL13-PE and Gd-albumin (n = 2), or co-infusion of IL13-PE (0.5 microg/mL) and Gd-albumin (n = 2). The animals were permitted to survive for up to 28 days before sacrifice and histologic assessment.RESULTS:
Rats showed no evidence of toxicity at all doses. Primates showed no toxicity at 0.25 or 0.5 microg/mL but showed clinical and histologic toxicity at 10 microg/mL. Quantitative autoradiography confirmed that Gd-albumin precisely tracked IL13-PE anatomic distribution and accurately showed the volume of distribution.CONCLUSIONS:
IL13-PE can be delivered safely and effectively to the primate brainstem at therapeutic concentrations and over clinically relevant volumes using convection-enhanced delivery. Moreover, the distribution of IL13-PE can be accurately tracked by co-infusion of Gd-albumin using real-time magnetic resonance imaging.
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Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
/
Tronco Encefálico
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Barreira Hematoencefálica
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ADP Ribose Transferases
/
Interleucina-13
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Fatores de Virulência
/
Exotoxinas
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article