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Sampson, JH, Brady, ML, Petry, NA, Croteau, D, Friedman, AH, Friedman, HS et al.. Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning. Neurosurgery 60(2 Suppl 1): ONS89-98; discussion ONS98

Department of Surgery, Duke University, Durham, North Carolina, United States
Neurosurgery (Impact Factor: 3.03). 03/2007; 60(2 Suppl 1):ONS89-98; discussion ONS98-9. DOI: 10.1227/01.NEU.0000249256.09289.5F
Source: PubMed

ABSTRACT Convection-enhanced delivery (CED) holds tremendous potential for drug delivery to the brain. However, little is known about the volume of distribution achieved within human brain tissue or how target anatomy and catheter positioning influence drug distribution. The primary objective of this study was to quantitatively describe the distribution of a high molecular weight agent by CED relative to target anatomy and catheter position in patients with malignant gliomas.
Seven adult patients with recurrent malignant gliomas underwent intracerebral infusion of the tumor-targeted cytotoxin, cintredekin besudotox, concurrently with 123I-labeled human serum albumin. High-resolution single-photon emission computed tomographic images were obtained at 24 and 48 hours and were coregistered with magnetic resonance imaging scans. The distribution of 123I-labeled human serum albumin relative to target anatomy and catheter position was analyzed.
Intracerebral CED infusions were well-tolerated and some resulted in a broad distribution of 123I-labeled human serum albumin, but target anatomy and catheter positioning had a significant influence on infusate distribution even within non-contrast-enhancing areas of brain. Intratumoral infusions were anisotropic and resulted in limited coverage of the enhancing tumor area and adjacent peritumoral regions.
CED has the potential to deliver high molecular weight agents into tumor-infiltrated brain parenchyma with volumes of distribution that are clinically relevant. Target tissue anatomy and catheter position are critical parameters in optimizing drug delivery.

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    • "CED has shown encouraging results in experimental animal models [56]. However, issues such as the limited amount of time CED can be applied [57], variable distribution, as well as safety concerns, render CED as a questionable mode of delivery of nanoparticles to glioma tissues [58, 59]. "
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    Oncotarget 03/2013; 4(3):378-96. · 6.63 Impact Factor
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    • "If catheters are inaccurately placed, leakage of infusate into the intraventricular spaces and subarachnoid will result in poor drug delivery and distribution [9]. Currently, catheters generate a certain amount of backflow where the fluid flow in a tissue-free region created by fluid pressure along the outer surface of the catheter [9] [10] [11]. In addition, any large (millimeter sized) bubbles may redirect the flow away from the catheter tip in unpredictable ways. "
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    ABSTRACT: The blood brain barrier (BBB) poses a significant challenge for drug delivery of macromolecules into the brain. Convection-enhanced delivery (CED) circumvents the BBB through direct intracerebral infusion using a hydrostatic pressure gradient to transfer therapeutic compounds. The efficacy of CED is dependent on the distribution of the therapeutic agent to the targeted region. Here we present a review of convection enhanced delivery of macromolecules, emphasizing the role of tracers in enabling effective delivery anddiscuss current challenges in the field.
    Current Drug Discovery Technologies 02/2012; 9(4). DOI:10.2174/157016312803305951
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    • "Recent clinical trials have shown the safety of CED in the treatment of Glioblastoma Multiforme (GBM) [5]–[7]. In addition, these trials have illustrated some of the technical challenges of CED and the need to monitor the process of convection to prevent toxicity on one hand and frank ineffectiveness due to limited convection on the other [8]. Adenoviral vectors or conditionally replicating adenoviruses (CRAds) have been used preclinically and clinically in a variety of intracranial diseases [9], [10]. "
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