Journal of Neuro-Oncology

, Volume 98, Issue 1, pp 1–7 | Cite as

Convection-enhanced delivery of free gadolinium with the recombinant immunotoxin MR1-1

  • Dale Ding
  • Charles W. Kanaly
  • Darrell D. Bigner
  • Thomas J. Cummings
  • James E. HerndonII
  • Ira Pastan
  • Raghu Raghavan
  • John H. SampsonEmail author
Laboratory Investigation - Human/Animal Tissue


A major obstacle in glioblastoma (GBM) therapy is the restrictive nature of the blood-brain barrier (BBB). Convection-enhanced delivery (CED) is a novel method of drug administration which allows direct parenchymal infusion of therapeutics, bypassing the BBB. MR1-1 is a novel recombinant immunotoxin that targets the GBM tumor-specific antigen EGFRvIII and can be delivered via CED infusion. However, drug distribution via CED varies dramatically, which necessitates active monitoring. Gadolinium conjugated to diethylenetriamine penta-acetic acid (Gd-DTPA) is a commonly used MRI contrast agent which can be co-infused with therapies using CED and may be useful in monitoring infusion leak and early distribution. Forty immunocompetent rats were implanted with intracerebral cannulas that were connected to osmotic pumps and subsequently randomized into four groups that each received 0.2% human serum albumin (HSA) mixed with a different experimental infusion: (1) 25 ng/ml MR1-1; (2) 0.1 μmol/ml Gd-DTPA; (3) 25 ng/ml MR1-1 and 0.1 μmol/ml Gd-DTPA; (4) 250 ng/ml MR1-1 and 0.1 μmol/ml Gd-DTPA. The rats were monitored clinically for 6 weeks then necropsied and histologically assessed for CNS toxicity. All rats survived the entirety of the study without clinical or histological toxicity attributable to the study drugs. There was no statistically significant difference in weight change over time among groups (P > 0.999). MR1-1 co-infused with Gd-DTPA via CED is safe in the long-term setting in a pre-clinical animal model. Our data supports the use of Gd-DTPA, as a surrogate tracer, co-infused with MR1-1 for drug distribution monitoring in patients with GBM.


Immunotoxins Brain Drug delivery systems glioblastoma Gadolinium 



We acknowledge the expert technical assistance provided by Gary Archer, Tracy Chewning, and April Coan. This research was supported in part by Duke University’s CTSA grant TL1RR024126 from National Center for Research Resources, National Institutes of Health and by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Dale Ding
    • 1
  • Charles W. Kanaly
    • 2
  • Darrell D. Bigner
    • 3
  • Thomas J. Cummings
    • 4
  • James E. HerndonII
    • 5
  • Ira Pastan
    • 6
  • Raghu Raghavan
    • 7
  • John H. Sampson
    • 8
    Email author
  1. 1.School of MedicineDuke University Medical Center, DUMCDurhamUSA
  2. 2.Division of Neurosurgery, Department of SurgeryDuke University Medical CenterDurhamUSA
  3. 3.Department of Pathology, Duke University Medical CenterThe Preston Robert Tisch Brain Tumor Center at DukeDurhamUSA
  4. 4.Department of PathologyDuke University Medical CenterDurhamUSA
  5. 5.Department of Biostatistics and BioinformaticsDuke University Medical CenterDurhamUSA
  6. 6.Laboratory of Molecular Biology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  7. 7.Therataxis, LLCBaltimoreUSA
  8. 8.Division of Neurosurgery, Department of SurgeryDuke University Medical Center, The Preston Robert Tisch Brain Tumor Center at DukeDurhamUSA

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