Longitudinal Monitoring of Gd-DTPA Following Convection Enhanced Delivery in the Brainstem

Umberto Tosi, Mark M Souweidane
World Neurosurgery 2020 February 3

BACKGROUND: Convection-enhanced delivery (CED) has been introduced into contemporary therapeutic strategies for incurable brain neoplasms as diffuse intrinsic pontine glioma (DIPG). Therapeutic benefit in part is predictably dependent upon drug distribution within tumor. However, therapeutics can rarely be detected through conventional imaging techniques. Co-infusion of the tracer Gadolinium-diethylenetriaminepentacetate (Gd-DTPA) has been advocated to monitor drug distributive features including volume (Vd), tumor coverage, and efflux during and after administration. The kinetics of Gd-DTPA are unclear as longitudinal MRI is rarely performed. Understanding these changes would have important implications related to the timing of diagnostic imaging and reliance on tracers as surrogates of pharmacokinetic drug monitoring.

CASE DESCRIPTION: The behavior of Gd-DTPA as a surrogate is presented in a time-dependent fashion as measured by repeated MRI based on the case of a child with recurrent DIPG treated with an oncolytic virus (ICOVIR-5) delivered by CED with co-infused Gd-DTPA (1 mM, for a volume of 2000 μL). Initial Vd / Vi was 1.46. Gd-DTPA was observed up to 18 hours post CED but not thereafter.

CONCLUSIONS: This longitudinal imaging assessment provides a rare opportunity to better characterize the kinetics of surrogate tracers delivered by CED to the brainstem, highlighting the importance of immediate and longitudinal monitoring.

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