A comparison of two contrast agents for dynamic contrast enhanced photoacoustic imaging in a preclinical model of breast cancer

Abstract Dynamic contrast enhanced photoacoustic imaging (DCE PAI) can measure vascular perfusion in preclinical tumor models by monitoring the wash-in and wash-out of an exogenous contrast agent in tumor tissue. Indocyanine green (ICG) is often used for DCE PAI studies, but this agent is amphiphilic and non-specifically binds to proteins, complicating pharmacokinetics analyses of tumor vascular perfusion. A fluorescent agent, ZW800-1, may be repurposed for PAI. ZW800-1 is more hydrophilic than ICG and therefore may be a superior contrast agent for DCE PAI studies. Herein, we compared ZW800-1 and ICG during phantom studies of PA spectra, signal amplitude and photostability. ZW800-1 demonstrated narrower PA spectral features, stronger signal, and less dependence on proteins than ICG, while maintaining comparable photostability in protein-rich media. We then performed a DCE PAI study with an orthotopic 4T1 model of breast cancer before and after treatment with an acute vascular disrupting agent, combretastatin A4 phosphate. In vivo pharmacokinetics measurements of tumor vascular perfusion showed a greater dynamic range with ZW800-1 than with ICG, resulting in statistically significant decreases at each time point after vascular disruption treatment when using ZW800-1, but not with ICG. Therefore, ZW800-1 is a superior contrast agent for DCE PAI studies.