Umberto Tosi1, Mark M Souweidane2. 1. Department of Neurosurgery, Weill Cornell Medicine, New York, New York, USA. 2. Department of Neurosurgery, Weill Cornell Medicine, New York, New York, USA; Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Electronic address: mmsouwei@med.cornell.edu.
Abstract
BACKGROUND: Convection-enhanced delivery (CED) has been introduced into contemporary therapeutic strategies for incurable brain neoplasms as diffuse intrinsic pontine glioma. Therapeutic benefit in part is predictably dependent on drug distribution within tumors. However, therapeutics can rarely be detected through conventional imaging techniques. Coinfusion of the tracer gadolinium-diethylenetriaminepentacetate (Gd-DTPA) has been advocated to monitor drug distributive features including volume, tumor coverage, and efflux during and after administration. The kinetics of Gd-DTPA are unclear as longitudinal magnetic resonance imaging 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 magnetic resonance imaging based on the case of a child with recurrent diffuse intrinsic pontine glioma treated with an oncolytic virus (ICOVIR-5) delivered by CED with coinfused 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.
BACKGROUND: Convection-enhanced delivery (CED) has been introduced into contemporary therapeutic strategies for incurable brain neoplasms as diffuse intrinsic pontine glioma. Therapeutic benefit in part is predictably dependent on drug distribution within tumors. However, therapeutics can rarely be detected through conventional imaging techniques. Coinfusion of the tracer gadolinium-diethylenetriaminepentacetate (Gd-DTPA) has been advocated to monitor drug distributive features including volume, tumor coverage, and efflux during and after administration. The kinetics of Gd-DTPA are unclear as longitudinal magnetic resonance imaging 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 magnetic resonance imaging based on the case of a child with recurrent diffuse intrinsic pontine glioma treated with an oncolytic virus (ICOVIR-5) delivered by CED with coinfused 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.
Authors: Chibueze D Nwagwu; Amanda V Immidisetti; Michael Y Jiang; Oluwasegun Adeagbo; David C Adamson; Anne-Marie Carbonell Journal: Pharmaceutics Date: 2021-04-15 Impact factor: 6.321