Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer

Abstract

Real-time in vivo CT scanning of CED of iopamidol appears to be safe, feasible, and suitable for monitoring convective delivery of drugs with certain features and low infusion volumes.

Convection enhanced delivery for treating brain tumors and selected neurological disorders: symposium review

“…It provides a clear picture with good correlation of intensity in Hounsfield units. Dr. Lonser described a study which examined the safety and utility of an iodine-based low-molecular weight surrogate tracers for CT performed during CED in four primates [16]. The distribution of the tracer was determined by realtime postinfusion CT as well as quantitative autoradiography of small molecules (sucrose-MW 359 D) or large molecules (dextran-MW 70 kD).…”

Convection-enhanced delivery to the central nervous system

“…Because convective distribution of an infusate occurs in the interstitial space, the distribution volume achieved by CED of a given infusate volume is inversely proportional to the size of the extracellular space available in the target tis- 22,54,58,63 Perfusion into the tightly compacted white matter fibers of the brainstem is associated with larger distribution volume to infusion volume ratios, generally in the range of 6:1 to 10:1. 60,72,99 This property of CED allows large, clinically relevant volumes of CNS tissue to be perfused relatively rapidly.…”

“…3). 3,16,22,25,27,29,59,76,106 Because CED relies on bulk flow and because most large-and many small-molecular-weight compounds distribute at a similar rate during the typical time course of CED, surrogate tracers that differ substantially in size from the putative therapeutic can often be used to track drug distribution over infusion volumes necessary to treat many neurological disorders.…”

“…68 Further, avoiding entrainment of intraparenchymal air that occurs with malleable infusion catheters upon removal of the rigid inner stylet needed for accurate placement of the tip is necessary to avoid preferential distribution in the tissue air pocket. These critical cannula properties have been achieved through the development of inner infusate cannula-outer guide cannula combinations, 22,31,62 hollow fiber tubes, 77,78 as well as step-design cannulae.…”

“…22 For these specific compounds, modeling has shown that for a desired V i (in ml), q i (in ml/min) must be chosen so that q i ≥ V i /600. From such empirical relationships, it is likely that many neurological disorders can be investigated with the expectation that the infusate volume required would be accurately tracked using a small-molecular-weight contrast agent-provided that the therapeutic compound, large or small, is negligibly reactive and confined to the extracellular space.…”