Molecular photoacoustic tomography of breast cancer using receptor targeted magnetic iron oxide nanoparticles as contrast agents

In this report, we present a breast imaging technique combining high-resolution near-infrared (NIR) light induced photoacoustic tomography (PAT) with NIR dye-labeled amino-terminal fragments of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (NIR830-ATF-IONP) for breast cancer imaging using an orthotopic mouse mammary tumor model. We show that accumulation of the targeted nanoparticles in the tumor led to photoacoustic contrast enhancement due to the high absorption of iron oxide nanoparticles (IONP). NIR fluorescence images were used to validate specific delivery of NIR830-ATF-IONP to mouse mammary tumors. We found that systemic delivery of the targeted IONP produced 4- and 10-fold enhancement in photoacoustic signals in the tumor, compared to the tumor of the mice that received non-targeted IONP or control mice. The use of targeted nanoparticles allowed imaging of tumors located as deep as 3.1 cm beneath the normal tissues. Our study indicates the potential of the combination of photoacoustic tomography and receptor-targeted NIR830-ATF-IONP as a clinical tool that can provide improved specificity and sensitivity for breast cancer detection. In vivo photoacoustic MAP and fluorescence images before and after injection. Micrographs were merged with fluorescence images taken 24 hours post injection with indicated agent (a, e, i). Panels b thru l. Photoacoustic [GRAPHICS] MAP images were merged with images of blood vessels before injection (b, f, j), and at 5 hours (c, g, k) and 24 hours (d, h, l) post injection.