(694b) Magnetic Nanoparticles for Multispectral Optoacoustic Imaging of Proteolytic Activity in the Tumor Microenvironment

Prostate Cancer (PCa) is the most diagnosed non-skin malignancy and the second leading cause of death from cancer among men in the United States. In order to achieve more effective therapy, early and accurate detection of prostate cancer is necessary to identify patients at high risk of disease progression. This allows for aggressive treatment to patients with tumors that carry certain metastatic potential. Unfortunately, current screening technologies for PCa, including the prostate-specific antigen (PSA) test, are limited by false-negatives and false-positives. A recent study showed that there is no PSA threshold that accurately predicts the presence or absence of PCa. Additionally, even when PCa is successfully detected, these screens provide no indication of the aggressiveness of the disease. Improved molecular imaging techniques, that are both quantitative and sensitive, and that can non-invasively detect processes deep within the human body are required to monitor changes which may be predictors of treatment outcomes.

The expression of matrix metalloproteinase-2 (MMP-2), an important tumor-associated protease, has been correlated with increasing metastatic potential in PCa and is therefore an attractive target for PCa targeting and diagnosis. We developed an MMP-2 sensitive, dual fluorochrome probe based on superparamagnetic iron oxide nanoparticles (SPIONs), with one fluorochrome (AF 700) that resisted proteolytic activation and thus served as an internal reference, while another optically distinct fluorochrome (AF 750) was conjugated to SPIONs through an MMP-2 sensitive peptide linker. We were able to quantify the presence of both fluorochromes using multispectral optoacoustic tomography (MSOT). The probe displayed sensitivity to MMP-2 activity in an MMP-2 overexpressing cell line in vitro and in vivo; slowly releasing AF 750 in low activity microenvironments and more rapidly in the presence of high MMP-2 activity. The MSOT ratio of AF 750 signal over AF 700 signal, which corrects for differences in the lesion size and depth, reflected the level of MMP-2 activity in the surrounding tissue; decreasing in areas of high MMP-2 activity, while remaining relatively constant in areas of low MMP-2 activity.