Continuous intraputamenal convection-enhanced delivery in adult rhesus macaques.
J Neurosurg
; 123(6): 1569-77, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-25932605
ABSTRACT
OBJECT Assessing the safety and feasibility of chronic delivery of compounds to the brain using convection-enhanced delivery (CED) is important for the further development of this important therapeutic technology. The objective of this study was to follow and model the distribution of a compound delivered by CED into the putamen of rhesus monkeys. METHODS:
The authors sequentially implanted catheters into 4 sites spanning the left and right putamen in each of 6 rhesus monkeys. The catheters were connected to implanted pumps, which were programmed to deliver a 5-mM solution of the MRI contrast agent Gd-DTPA at 0.1 µl/minute for 7 days and 0.3 µl/minute for an additional 7 days. The animals were followed for 28 days per implant cycle during which they were periodically examined with MRI.RESULTS:
All animals survived the 4 surgeries with no deficits in behavior. Compared with acute infusion, the volume of distribution (Vd) increased 2-fold with 7 days of chronic infusion. Increasing the flow rate 3-fold over the next week increased the Vd an additional 3-fold. Following withdrawal of the compound, the half-life of Gd-DTPA in the brain was estimated as 3.1 days based on first-order pharmacokinetics. Histological assessment of the brain showed minimal tissue damage limited to the insertion site.CONCLUSIONS:
These results demonstrate several important features in the development of a chronically implanted pump and catheter system 1) the ability to place catheters accurately in a predetermined target; 2) the ability to deliver compounds in a chronic fashion to the putamen; and 3) the use of MRI and MR visible tracers to follow the evolution of the infusion volume over time.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Putamen
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Bombas de Infusão Implantáveis
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Sistemas de Liberação de Medicamentos
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Convecção
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Meios de Contraste
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Gadolínio DTPA
Limite:
Animals
Idioma:
En
Revista:
J Neurosurg
Ano de publicação:
2015
Tipo de documento:
Article