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Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: Descriptive effects of target anatomy and catheter positioning

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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    • "With the increasing use of CED in clinical neurosurgery (Kunwar et al., 2007; Lonser et al., 2007), investigators have sought to visualize the delivery of therapeutics intra-operatively. CED visualization with the aid of novel contrast materials co-infused with therapeutic agents has recently been investigated in rodents (Saito et al., 2004), non-human primates (Lonser et al., 2002; Murad et al., 2007; Saito et al., 2005) and humans (Lonser et al., 2007; Sampson et al., 2007). Real-time convective delivery (RCD) utilizes MRI to visualize the CED process with the aid of Gadolinium-loaded liposomes (GDL) to co-distribute with the therapeutic being delivered. "
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