title: Colocalization of gadolinium-diethylene triamine pentaacetic acid with high-molecular-weight molecules after intracerebral convection-enhanced delivery in humans.
abstract: BACKGROUND
  Convection-enhanced delivery (CED) permits site-specific therapeutic drug delivery within interstitial spaces at increased dosages through circumvention of the blood-brain barrier. CED is currently limited by suboptimal methodologies for monitoring the delivery of therapeutic agents that would permit technical optimization and enhanced therapeutic efficacy.
  
  
  OBJECTIVE
  To determine whether a readily available small-molecule MRI contrast agent, gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), could effectively track the distribution of larger therapeutic agents.
  
  
  METHODS
  Gd-DTPA was coinfused with the larger molecular tracer, I-labeled human serum albumin (I-HSA), during CED of an EGFRvIII-specific immunotoxin as part of treatment for a patient with glioblastoma.
  
  
  RESULTS
  Infusion of both tracers was safe in this patient. Analysis of both Gd-DTPA and I-HSA during and after infusion revealed a high degree of anatomical and volumetric overlap.
  
  
  CONCLUSIONS
  Gd-DTPA may be able to accurately demonstrate the anatomic and volumetric distribution of large molecules used for antitumor therapy with high resolution and in combination with fluid-attenuated inversion recovery (FLAIR) imaging, and provide additional information about leaks into cerebrospinal fluid spaces and resection cavities. Similar studies should be performed in additional patients to validate our findings and help refine the methodologies we used.
authors: Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. john.sampson@duke.edu
authors: John H
authors: JH
authors: Sampson
authors: Martin
authors: M
authors: Brady
authors: Raghu
authors: R
authors: Raghavan
authors: Ankit I
authors: AI
authors: Mehta
authors: Allan H
authors: AH
authors: Friedman
authors: David A
authors: DA
authors: Reardon
authors: Neil A
authors: NA
authors: Petry
authors: Daniel P
authors: DP
authors: Barboriak
authors: Terence Z
authors: TZ
authors: Wong
authors: Michael R
authors: MR
authors: Zalutsky
authors: Denise
authors: D
authors: Lally-Goss
authors: Darell D
authors: DD
authors: Bigner
mesh_terms: D000465:Algorithms; D001254:Astrocytoma / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D003131:Combined Modality Therapy; D003287:Contrast Media; D018481:Convection; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D019786:Gadolinium DTPA / Q000008:administration & dosage*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012711:Serum Albumin, Radio-Iodinated; D014055:Tomography, Emission-Computed
chemical_list: D003287:Contrast Media; D012711:Serum Albumin, Radio-Iodinated; D019786:Gadolinium DTPA