HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sampson, J. H. Articles by Pedain, C. Search for Related Content PubMed PubMed Citation Articles by Sampson, J. H. Articles by Pedain, C. Social Bookmarking                      What's this?

Induction of Hyperintense Signal on T2-Weighted MR Images Correlates with Infusion Distribution from Intracerebral Convection-Enhanced Delivery of a Tumor-Targeted Cytotoxin

¹ Department of Surgery, Duke University Medical Center, Durham, NC 27710.
² Therataxis, Inc., Baltimore, MD 21218.
³ Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC 27710.
⁴ NeoPharm, Inc., Waukegan, IL 60085.
⁵ BrainLAB AG, Feldkirchen, Germany.
⁶ Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
⁷ Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852.

OBJECTIVE. Convection-enhanced delivery is a promising approach to intracerebral drug delivery in which a fluid pressure gradient is used to infuse therapeutic macromolecules through an indwelling catheter into the interstitial spaces of the brain. Our purpose was to test the hypothesis that hyperintense signal changes on T2-weighted images produced by such infusions can be used to track drug distribution.

SUBJECTS AND METHODS. Seven adults with recurrent malignant glioma underwent concurrent intracerebral infusions of the tumor-targeted cytotoxin cintredekin besudotox and ¹²³I-labeled human serum albumin. The agents were administered through a total of 18 catheters among the seven patients. Adequacy of distribution of drug was determined by evidence of distribution of ¹²³I-labeled human serum albumin on SPECT images coregistered with MR images. Qualitative analysis was performed by three blinded observers. Quantitative analysis also was performed.

RESULTS. Infusions into 12 catheters produced intraparenchymal distribution as seen on SPECT images, but infusions into six catheters did not. At qualitative assessment of signal changes on MR images, reviewers correctly predicted which catheters would produce extraparenchymal distribution and which catheters would produce parenchymal distribution. Of the 12 infusions that produced intraparenchymal distribution, four catheters had been placed in regions of relatively normal signal intensity and produced regions of newly increased signal intensity, the volume of which highly correlated with the volume and geometry of distribution on SPECT (r² = 0.9502). Eight infusions that produced intraparenchymal distribution were performed in regions of preexisting hyperintense signal. In these brains, additional signal changes were always produced, but quantitative correlations between areas of newly increased signal intensity and the volume and geometry of distribution on SPECT could not be established.

CONCLUSION. Convection-enhanced infusions frequently do not provide intraparenchymal drug distribution, and these failures can be identified with MRI soon after infusion. When infusions are performed into regions of normal signal intensity, development of hyperintense signal change strongly correlates with the volume and geometry of distribution of infusate.

Keywords: brain • convection-enhanced delivery • drug delivery • glioma • MRI • oncology

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?