Global HDO uptake in human glioma xenografts is related to the perfused capillary distribution

The aim of this study is to evaluate the existence of a possible relationsh ip between global deuterium-labeled water (HDO) uptake rates and the diffus ion geometry of human glioma xenografts in nude mice. HDO diffusion times i n the whole extravascular tumor volume were estimated by combining quantita tive H-1-MR diffusion imaging and morphometric analysis of intercapillary d istances in two tumor lines with a different perfused vascular architecture , HDO uptake was measured independently using H-2-magnetic resonance spectr oscopy. Time constants of HDO-uptake curves ( tau) were compared to estimat ions of maximum HDO diffusion times (t(difmax)). Tumors with a homogeneousl y perfused capillary distribution showed a monoexponential HDO uptake. The t(dilmax) was comparable to tau values of HDO uptake curves: t(dlfmax) vari ed between 74 and 368 sec and the range of tau Values was 115-370 sec. Hete rogeneously perfused tumors had a bi-exponential HDO uptake with tdifmax in between the tau values of the fast and slow uptake phase. These findings i ndicate that the global HDO uptake is related to the perfused capillary dis tribution in human glioma xenografts. That HDO uptake rates indeed can depe nd on the perfused capillary distribution was substantiated in experiments with two-dimensional (2D) models. In these models with a diffusion-limited HDO uptake, HDO uptake curves could be approximated by curves derived from 2D HDO diffusion simulations. (C) 1999 Wiley-Liss, Inc.