Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin.
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.


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.


CONCLUSIONS
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.
Sampson
John H
JH
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Raghavan
Raghu
R
Provenzale
James M
JM
Croteau
David
D
Reardon
David A
DA
Coleman
R Edward
RE
Rodríguez Ponce
Inmaculada
I
Pastan
Ira
I
Puri
Raj K
RK
Pedain
Christoph
C
D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods; D005098:Exotoxins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics; D007261:Infusions, Intra-Arterial; D018793:Interleukin-13 / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D005098:Exotoxins; C521502:IL13-PE38; D000922:Immunotoxins; D018793:Interleukin-13; D011993:Recombinant Fusion Proteins