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

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 10 April 2010

Abstract

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.

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Acknowledgements

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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Authors and Affiliations

  1. School of Medicine, Duke University Medical Center, DUMC, Box 3050, 220 Sands Building, Research Drive, Durham, NC, 27710, USA

    Dale Ding

  2. Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Box 3050, 220 Sands Building, Research Drive, Durham, NC, 27710, USA

    Charles W. Kanaly

  3. Department of Pathology, Duke University Medical Center, The Preston Robert Tisch Brain Tumor Center at Duke, Box 3156, Durham, NC, 27710, USA

    Darrell D. Bigner

  4. Department of Pathology, Duke University Medical Center, Box 3712, Durham, NC, 27710, USA

    Thomas J. Cummings

  5. Department of Biostatistics and Bioinformatics, Duke University Medical Center, 8034 Hock Plaza, Durham, NC, 27710, USA

    James E. Herndon II

  6. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Ira Pastan

  7. Therataxis, LLC, 1101 East 33rd Street, Suite B305, Baltimore, MD, 21218, USA

    Raghu Raghavan

  8. Division of Neurosurgery, Department of Surgery, Duke University Medical Center, The Preston Robert Tisch Brain Tumor Center at Duke, Box 3050, 220 Sands Building, Research Drive, Durham, NC, 27710, USA

    John H. Sampson

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  1. Dale Ding
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An erratum to this article can be found at http://dx.doi.org/10.1007/s11060-010-0183-z

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Ding, D., Kanaly, C.W., Bigner, D.D. et al. Convection-enhanced delivery of free gadolinium with the recombinant immunotoxin MR1-1. J Neurooncol 98, 1–7 (2010). https://doi.org/10.1007/s11060-009-0046-7

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  • DOI: https://doi.org/10.1007/s11060-009-0046-7

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