Review of methods used to study oxygen transport at the microcirculatory level

Abstract

The existence of hypoxic regions in tumors has long been recognized as a key factor leading to radiation resistance. More recently, it has been found that low oxygen levels also affect drug resistance, angiogenesis, cytokine production, cell cycle control, apoptosis, and metastatic propensity of tumors. Until now, most approaches to eliminating hypoxia have been empirical. However, improved understanding of the underlying mechanisms may permit the development of more soundly based, effective approaches. As discussed in this review, critical evaluation of the factors governing oxygen transport in tumors requires a thorough understanding of the methods used to study this process. Many experimental methodologies can be used to address these issues. In this review, the emphasis is placed on techniques that measure parameters on the scale of the diffusion distance of oxygen. Studies at the microregional level provide the most detailed physiological information on such processes. Over the past few years, significant progress in technology has allowed us to measure tumor oxygenation, yet spatial and temporal heterogeneities continue to provide significant challenges to obtaining clear knowledge of oxygen transport. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 237–255 (2000). © 2000 Wiley‐Liss, Inc.

Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

“…DCE-MRI was compared with invasive pO 2 mapping. The fluorescence lifetime method we have used to measure pO2 has several advantages over the Eppendorf device, including absence of oxygen consumption and increased accuracy at low oxygen tensions common in neoplastic tissue (23). We chose to study post-RT effects relatively early to reflect clinical practice, with surgery after short term RT being usually performed within 1 week after the end of therapy.…”

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

“…It has been used as the 'gold standard' for measurement of tissue oxygenation. 53,54 The major problem of this technique is that it cannot make repeated measurements in the same position because it must be moved to minimize oxygen consumption by the electrode itself. Alternatively, recessed tip microelectrodes as compared with the Eppendorf 1 system, permit continuous recordings of tissue oxygenation without moving the probe.…”

Temporal heterogeneity in oxygen tension in human melanoma xenografts

“…Steep gradients in pO 2 and pO 2 values ranging from 0 mmHg to those found in welloxygenated normal tissues are characteristic features of tumours, implying that tumour tissues may show extensive spatial heterogeneity in cellular radiation sensitivity (Wouters and Brown, 1997) and hypoxia-induced gene expression (Acker and Plate, 2002;Harris, 2002). In contrast, studies of the temporal heterogeneity in pO 2 in tumours are sparse (Dewhirst et al, 2000). However, examinations of fluctuations in microvessel blood flow in window chamber tumours and measurements of the kinetics of red blood cell flux in experimental and human solid tumours by laser Doppler flowmetry have suggested that temporal heterogeneity in pO 2 and acute hypoxia are common events in tumour tissues (Endrich et al, 1979;Brizel et al, 1993;Chaplin and Hill, 1995;Hill et al, 1996).…”

“…The low number of investigations of the temporal heterogeneity in pO 2 in tumours most likely reflects that adequate equipment for measurement of fluctuations in pO 2 in tissues has not been commercially available (Dewhirst et al, 2000). A new oxygensensing device, the OxyLite system, was marketed recently (Young et al, 1996;Griffiths and Robinson, 1999).…”