title: Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina 27710, USA. john.sampson@duke.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: Martin L
authors.initials: ML
authors.lastname: Brady
authors.forename: Neil A
authors.initials: NA
authors.lastname: Petry
authors.forename: David
authors.initials: D
authors.lastname: Croteau
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: Terence
authors.initials: T
authors.lastname: Wong
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.forename: Raj K
authors.initials: RK
authors.lastname: Puri
authors.forename: Christoph
authors.initials: C
authors.lastname: Pedain
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D002404:Catheterization; D018481:Convection; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D005098:Exotoxins / Q000008:administration & dosage* / Q000009:adverse effects; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007276:Injections, Intraventricular; D018793:Interleukin-13 / Q000008:administration & dosage* / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010865:Pilot Projects; D011993:Recombinant Fusion Proteins; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000970:Antineoplastic Agents; D005098:Exotoxins; C521502:IL13-PE38; D018793:Interleukin-13; D011993:Recombinant Fusion Proteins