Introduction:
For chemical analysis, photoacoustic (PA) imaging with polyacrylamide (PAA) nanoparticle (NP) based contrast agent has been developed for tracking an altered metabolic state such as acidosis (low pH), hypoxia (low oxygen), and/or hyperkalemia (high potassium) in tumors. For pH and potassium imaging, we developed quantitative imaging techniques combining PA multi-wavelengths with ratio metric imaging methods. And, for oxygen imaging, we utilized lifetime-based oxygen sensing techniques.
The advanced study is focused on PA chemical imaging for guiding cancer therapy. As each chemical status (oxygen, pH and potassium concentrations) is strongly relevant to cancer progress and response to therapy (radio-, chemo- and immuno-therapy), a non-invasive, sensitive, and reliable approach for evaluating their temporal and spatial distributions in the tumor microenvironment (TME) in vivo is desirable. We apply the PA chemical imaging to predict a given tumor’s response to therapy. At first, we provide PA oxygen imaging to both predict the efficacy of radiation therapy for a given tumor and identify treatment- regions within the TME. And the study for comparing pH imaging and chemotherapy efficacy is currently underway.
Example results:
Figure 1. Quantitative pH images. (A) Spectroscopic optical absorption of oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb) and SNARF-PAA NPs at different pH levels. (D) pH image of in vivo tumor on a gray scale US image. (E) PA image of blood oxygen saturation. (Jo, J., et al. Nat. Commun. 2017, 8, 471.)
Figure 2. Quantitative tissue oxygen images. (A) PA lifetime-based oxygen imaging schematic. After injection of G2-PAA NPs, the decay rate calculated from PA images at 10-50 µs delays indicates oxygen concentration. (B) PA oxygen images of in vivo tumor. (C) PA oxygen images of in vivo thigh muscle. (Jo, J., et al., ACS Nano. 2019, 13, 14024)
Figure 3. Comparing similarity of oxygen map and radiation therapy effect. (A) Experimental setup. The high oxygen level and the DNA damaged area are compared. (B)(C) PA oxygen maps of in vivo tumors. (D)(E) H2AX stained histology microscopy images showing DNA damages by radiotherapy. (Jo, J., et al. ACS Nano. 2023)