Abstract
Phosphorescent lifetime imaging was employed to measure the spatial and temporal distribution of oxygen partial pressure in tissue under the coverslip of a mammary window chamber breast cancer mouse model. A thin platinum-porphyrin coating, whose phosphorescent lifetime varies monotonically with oxygen partial pressure, was applied to the coverslip surface. Dynamic temporal responses to induced modulations in oxygenation levels were measured using this approach.
Highlights
Tumor hypoxia has important implications in terms of disease progression, aggressiveness, and treatment response [1,2]
The mammary window chamber (MWC) model that we have developed is orthotopic, allowing breast cancer tumors to develop in their natural environment, and does not impose restrictions on the development of the tumor in three-dimensions [10]
As described in the methods, multiple experiments were performed where tissue oxygenation levels were modulated. This was done to demonstrate the ability of the MWC coating to measure physiologically relevant changes in tissue pO2 in vivo. 3.1 Modulation with gas Phosphorescence lifetime maps and subsequent pO2 maps were derived from data acquired while the gas mixture of isoflurane anesthesia was modified
Summary
Tumor hypoxia has important implications in terms of disease progression, aggressiveness, and treatment response [1,2]. Two of the most common approaches to oxygen measurement include insertion of pO2 needle electrode probes and administration of nitroimidazoles (e.g., pimonidazole) [3,4]. Nitroimidazoles are administered IV or IP and are subject to delivery limitations in reaching the target tissue site. Tissue biopsy is destructive and limited to a measurement at a single time point [5]. Radiolabeled versions of nitroimidazoles have been developed [6,7]. While potentially this eliminates the need for tissue removal, the radiolabeled agent approach still presents a temporal snapshot of oxygenation levels and is dependent upon successful delivery of agent to the tissue of interest
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