Magnetic Resonance Imaging-Based Assessment of Gadolinium-Conjugated Diethylenetriamine Penta-Acetic Acid Test-Infusion in Detecting Dysfunction of Convection-Enhanced Delivery Catheters

Background In a phase 1 trial conducted at our institute, convection-enhanced delivery (CED) was used to administrate the Delta-24-RGD adenovirus in patients with a recurrent glioblastoma multiforme. Infusion of the virus was preceded by a gadolinium-conjugated diethylenetriamine penta-acetic acid (Gd-DTPA) test-infusion. In the present study, we analyzed the results of Gd-DTPA test infusion through 50 catheters. Methods Thirteen adults with a recurrent glioblastoma multiforme were enrolled in a larger phase 1 multicenter, dose-finding study, in which a conditionally replication-competent adenovirus was administered by CED. Up to 4 infusion catheters per patient were placed intra- and/or peritumorally. Before infusion of the virus, a Gd-DTPA infusion was performed for 6 hours, directly followed by a MRI scan. The MRIs were evaluated for catheter position, Gd-DTPA distribution outcome, and contrast leakage. Results Leakage of Gd-DTPA into the cerebrospinal fluid was detected in 17 of the 50 catheters (34%). Sulcus crossing was the most frequent cause of leakage. In 8 cases, leakage could only be detected on the fluid-attenuated inversion recovery sequence. Nonleaking catheters showed a significantly larger Gd-DTPA distribution fraction (volume of distribution/volume of infusion) than leaking catheters (P = 0.009). A significantly lower volume of distribution/volume of infusion was observed in intratumoral catheters, compared with peritumoral catheters (P = 0.004). Gd-DTPA test infusion did not result in significant changes in Karnofsky Performance Score and Neurological Status. Conclusions Pre-CED treatment infusion of Gd-DTPA is an adequate and safe method to identify dysfunctional catheters. The use of an optimized drug delivery catheter is necessary to reduce leakage and improve the efficacy of intracerebral drug infusion.

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