Probing the in vivo changes in oxygen saturation with photoacoustic imaging as a non-invasive means of assessing treatment progression

摘要

In-vivo photoacoustic estimations of tumor oxygenation were used to assess the therapeutic efficacy of a thermosensitive liposome treatment in a pre-clinical mouse model. The treated group (n = 12) was administered doxorubicin-loaded, heat sensitive liposomes and exposed to mild hyperthermia (43°C) in order to deliver doxorubicin locally within the tumor micro-vessels. Control groups received systemic doxorubicin (n = 7) or saline (n = 12). The changes in tumor blood vessels after treatment were probed by analyzing the frequency content of the photoacoustic radiofrequency signals. Tumor oxygenation dropped by 15-20% during the first 30 minutes post-treatment when the tumors were exposed to encapsulated (Heat-Activated cyToxic - HaT-DOX) or free doxorubicin (DOX). The early (30 minutes to 5 hours) decrease in oxygen saturation strongly correlated to the reduction in tumor size assessed by caliper measurements. Control animals did not exhibit significant changes in tumor oxygenation at the early time points. The oxygenation at 7 days increased significantly for all groups. Measurements of the spectral slope from the normalized power spectra of the photoacoustic signals could also be used to differentiate between responder and non-responder mice. The results of this study suggest that photoacoustic imaging of tumors undergoing vascular-targeted cancer therapy can be used to assess treatment response early (hours) post-treatment through a combined analysis of oxygen saturation and photoacoustic radiofrequency spectroscopy.