Dynamic response of breast tumor oxygenation to hyperoxic respiratory challenge monitored with three oxygen-sensitive parameters

Abstract

The simultaneous measurement of three oxygen-sensitive parameters [arterial hemoglobin oxygen saturation (SaO2), tumor vascular-oxygenated hemoglobin concentration ([HbO2]), and tumor oxygen tension (pO2)] in response to hyperoxic respiratory challenge is demonstrated in rat breast tumors. The effects of two hyperoxic gases [oxygen and carbogen (5% CO2 and 95% O2)] were compared, by use of two groups of Fisher rats with subcutaneous 13762NF breast tumors implanted in pedicles on the foreback. Two different gas-inhalation sequences were compared, i.e., air-carbogen-air-oxygen-air and air-oxygen-air-carbogen-air. The results demonstrate that both of the inhaled, hyperoxic gases significantly improved the tumor oxygen status. All three parameters displayed similar dynamic response to hyperoxic gas interventions, but with different response times: the fastest for arterial SaO2, followed by biphasic changes in tumor vascular [HbO2], and then delayed responses for pO2. Both of the gases induced similar changes in vascular oxygenation and regional tissue pO2 in the rat tumors, and changes in [HbO2] and mean pO2 showed a linear correlation with large standard deviations, which presumably results from global versus local measurements. Indeed, the pO2 data revealed hetergeneous regional response to hyperoxic interventions. Although preliminary near-infrared measurements had been demonstrated previously in this model, the addition of the pO2 optical fiber probes provides a link between the noninvasive relative measurements of vascular phenomena based on endogenous reporter molecules, with the quantitative, albeit, invasive pO2 determinations.

Simultaneous Monitoring of Vascular Oxygenation and Tissue Oxygen Tension of Breast Tumors Under Hyperbaric Oxygen Exposure

“…This mathematical model has been utilized well to explain our experimental animal studies (Liu et al 2000, Gu et al 2003, Kim et al 2003b. Moreover, it has been supported by computer simulations (Kim and Liu 2005) and phantom study (Kim and Liu 2004) that the bi-phasic or bi-exponential feature can be well present if both a slow and a fast perfusion of flow co-exist within the interrogated area or volume by the NIR source and detector.…”

“…Due to the deep penetration depth and biochemical specificity of NIRS, it has been widely applied for quantitative measurements of cerebral oxygenation (Delpy andCope 1997, Yodh andBoas 2003) and blood oxygenation in muscles in vivo (Homma et al 1996). Recently, NIRS has been also used to monitor tumour vascular oxygenation with respect to interventions (Hull et al 1999, Liu et al 2000, Gu et al 2003. With notable exceptions (Chance 1997, Dehghani et al 2004, Shah et al 2004, NIRS currently lacks spatial resolution, and thus, the utility of global measurements requires validation, given the well-documented heterogeneity of tumour oxygenation.…”

“…The sensitivity and specificity analysis suggests that NIRS may identify clinically relevant hypoxia, even when its spatial extent is below the resolution limit of the NIRS technique. We have previously investigated correlates between pO2 assessed by electrodes , Kim et al 2003b or fibre-optic probes and NIRS (Gu et al 2003). On occasion, there was a good correlation between global vascular oxygenation assessed and local PO2 at individual locations, but often, disparate behaviour was observed.…”

VatuximabTM: Optimizing Therapeutic Strategies for Prostate Cancer Based on Dynamic MR Tumor Oximetry

“…We have used FREDOM to examine the effects of vascular targeting agents [36,267], vasoactive agents [215] and hyperoxic gases [10,200,[212][213][214][215][216][217][268][269][270]. We have shown that measurements are consistent with sequential determinations made using electrodes [271,272] and fiber optic probes (FOXY TM and OxyLite ) [201,216]. Repeat measurements are highly reproducible and generally quite stable in tumors under baseline conditions.…”

“…Other modalities provide an indication of hypoxia [197,198]. In many cases, there is a desire to measure pO 2 directly and this may be achieved using polarographic electrodes [199,200], fiber optic probes [201], free radical probes with electron spin resonance (ESR) [191,202], or PFC probes with NMR [9,10], as described below.…”