Photoacoustic imaging to optimize tumor delivery of human hemoglobin-derived oxygen carriers and subsequent photodynamic therapy.

Photodynamic therapy shows promise as a minimally invasive, tumor-selective treatment, but it requires the presence of oxygen, often scarce within tumors. Such therapy can be potentiated by delivering hemoglobin-based oxygen carriers into tumors, but the appropriate carrier concentration and interval between their delivery and photodynamic therapy must be selected for a given treatment setting. Here we exploited the ability of photoacoustic imaging to non-invasively measure intratumoral oxygenation in order to optimize the delivery of oxygen carriers derived from human hemoglobin. In tumor-bearing mice, the largest increase in intratumoral oxygen saturation relative to baseline occurred 6 h after injection of carriers at 600 mg/kg, and photodynamic therapy under this condition significantly magnified the effects on tumor apoptosis and growth. The oxygen carriers induced no obvious off-target toxicity, and their oxygenating effects declined substantially by 24 h after injection, indicating that the oxygenation response was transient under the sampled conditions. Our results illustrate the power of photoacoustic imaging for optimizing the intratumoral delivery of hemoglobin-based oxygen carriers and subsequent photodynamic therapy. Our results offer preclinical evidence that oxygen carriers derived from human hemoglobin may be more biocompatible than oxygen-carrying nanoparticles.