Noninvasive measurement of microvascular and interstitial oxygen profiles in a human tumor in SCID mice.

Abstract

Simultaneous measurements of intravascular and interstitial oxygen partial pressure (Po2) in any tissue have not previously been reported, despite the importance of oxygen in health and in disease. This is due to the limitations of current techniques, both invasive and noninvasive. We have optically measured microscopic profiles of Po2 with high spatial resolution in subcutaneous tissue and transplanted tumors in mice by combining an oxygen-dependent phosphorescence quenching method and a transparent tissue preparation. The strengths of our approach include the ability to follow Po2 in the same location for several weeks and to relate these measurements to local blood flow and vascular architecture. Our results show that (i) Po2 values in blood vessels in well-vascularized regions of a human colon adenocarcinoma xenograft are comparable to those in surrounding arterioles and venules, (i) carbogen (95% 02/5% CO2) breathing increases microvascular P02 in tumors, and (iii) in unanesthetized and anesthetized mice P02 drops to hypoxic values at <200 Am from isolated vessels but drops by <5 mmHg (1 mmlg = 133 Pa) in highiy vascularized tumor regions. Our method should permit noninvasive evaluations of oxygen-modifying agents and offer further mechanistic information about tumor pathophysiology in tissue preparations where the surface of the tissue can be observed.

Vascular remodelling of an arterio-venous blood vessel network during solid tumour growth

“…50% of the peak values. These are typical observations in (Carmeliet and Jain, 2000;Torres Filho et al, 1994).…”

Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E–Deficient Mice

“…Comparisons of the lamellar structure across many species suggested that a minimal vessel wall thickness was required for the presence of vasa vasorum. 21 Intravital studies of tissue oxygenation in tumors demonstrated that significant hypoxia and acidosis occur when the distance from a capillary exceeds 100 m. 22 Given the thin media of the murine aorta, only relatively large lesions may exceed the limit at which growing plaques require additional sources of perfusion beyond the artery lumen and adventitial vessels. Our results are consistent with this assumption.…”

Fluorescence ratio imaging of interstitial pH in solid tumours: effect of glucose on spatial and temporal gradients

“…In the future, the FRIM technique may be further adapted and used in combination with a phosphorescence quenching technique (Torres-Filho et al, 1994), to evaluate noninvasively extracellular pH, intracellular pH and P02 in solid tumours transplanted in the dorsal chambers in mice.…”