Effect of concentration on the accuracy of convective imaging distribution of a gadolinium-based surrogate tracer

Abstract

Object: Accurate real-time imaging of coinfused surrogate tracers can be used to determine the convective distribution of therapeutic agents. To assess the effect that a concentration of a Gd-based surrogate tracer has on the accuracy of determining the convective distribution, the authors infused different concentrations of Gd-diethylenetriamine pentaacetic acid (DTPA) in primates during MR imaging.

Methods: Five nonhuman primates underwent convective infusion (1 or 5 mM, 21-65 μl) of Gd-DTPA alone, Gd-DTPA and (14)C-sucrose, or Gd-DTPA and (14)C-dextran into the bilateral striata. Animals underwent real-time MR imaging during infusion (5 animals) and autoradiographic analysis (2 animals).

Results: Gadolinium-DTPA could be seen filling the striata at either concentration (1 or 5 mM) on real-time MR imaging. While the volume of distribution (Vd) increased linearly with the volume of infusion (Vi) for both concentrations of tracer (1 mM: R(2) = 0.83; 5 mM: R(2) = 0.96), the Vd/Vi ratio was significantly (p < 0.0001) less for the 1-mM (2.3 ± 1.0) as compared with the 5-mM (7.4 ± 1.9) concentration. Autoradiographic and MR volumetric analysis revealed that the 5-mM concentration most accurately estimated the Vd for both small (sucrose [359 D], 12% difference between imaging and autoradiographic distribution) and large (dextran [70 kD], 0.2% difference) molecules compared with the 1-mM concentration (sucrose, 65% difference; dextran, 68% difference).

Conclusions: The concentration of infused Gd-DTPA plays a critical role in accurately assessing the distribution of molecules delivered by CED. A 5-mM concentration of Gd-DTPA most accurately estimated the Vd over a wide range of molecular sizes.

Fig. 1

Magnetic resonance images of serial dilutions of Gd-DTPA in vitro (mM concentration).

Fig. 2

Axial real-time T1-weighted MR image of bilateral striata with 1 mM (arrowhead) and 5 mM (arrow) of Gd-DTPA revealing reduced

Fig. 3

Graph demonstrating the relationship between Vd and Vi. There was a highly linear relationship between Vd (determined by MR imaging) and Vi of Gd-DTPA at the 1-mM (R² = 0.83, gray circles) and 5-mM concentration (R² = 0.96, black circles). The mean Vd/Vi ratio (7.4 ± 0.9) for the 5-mM concentration was significantly (p < 0.05) higher than that for the 1-mM concentration (2.3 ± 1.0).

Fig. 4

Quantitative analysis of the specific activity (concentration) of ¹⁴C-sucrose (left) and ¹⁴C-dextran (right) across perfused regions of bilateral striata revealing a square-shaped distribution of substrate of both molecules. PSL-BG = photostimulated luminescence given per area (concentration of radiation).

Fig. 5

Graph showing Gd-DTPA postinfusion Vd. The Vd increased (maximal increase 30 minutes after infusion) significantly (p < 0.05) more for the 5-mM concentration (96% increase over Vd at infusion cessation, black circles) than for the 1-mM concentration (61% increase, gray circles).