Multispectral Optoacoustic Tomography (MSOT) for Imaging of Pharmacokinetics and Biodistribution of Pegylated Superparamagnetic Iron Oxide Nanoparticles

Multispectral optoacoustic tomography (MSOT) has emerged as a leading technology that uses photoacoustic imaging for high-resolution imaging of cancer. MSOT combines the high contrast of optical imaging with the high resolution and great penetration depth of ultrasound imaging. It can detect sound waves that are produced following illumination of target tissue by multiple wavelengths to characterize the distribution of multiple endogenous and exogenous molecules simultaneously. MSOT is noninvasive and fast; therefore, it can image dynamic processes in real-time with high temporal resolution.

We used MSOT imaging to compare the in vivo pharmacokinetics, i.e. disappearance rate from circulation, and biodistribution profiles of Cy 7 fluorophore conjugated superparamagnetic iron oxide nanoparticles (Cy7-SPIONs) coated with three different sizes of polyethylene glycol (PEG). We used image reconstruction and spectral unmixing algorithms to visualize and quantify the concentration of Cy7-SPION in circulation and in organs of elimination. To validate the results, we collected blood and tissue samples, and quantified Cy7-SPIONs concentrations using electron spin resonance (ESR). The size of PEG, which alters the surface properties of SPIONs, significantly affected the pharmacokinetics and biodistribution profiles of Cy7-SPIONs.

In another study, we developed RGD-functionalized Cy7-SPIONs (RGD-Cy7-SPIONs) for in vivo MSOT imaging of αvβ3 integrin positive MCF-7 breast tumor-bearing mice. A significant increase in MSOT signal was observed at the tumor site with RGD-Cy7-SPIONs, compared to nontargeted Cy7-SPIONs. MSOT demonstrated superior sensitivity in tumor detection compared to two-dimensional fluorescent imaging.