Diagnostic imaging of aggressive cancer with a high stroma content may benefit from the use of imaging contrast agents targeted with peptides that have high binding affinity to the extracellular matrix (ECM). In this study, we report the use of superparamagnetic iron-oxide nanoparticles (IO-NP) conjugated to a nonapeptide, CSGRRSSKC (CSG), which specifically binds to the laminin-nidogen-1 complex in tumours. We show that CSG-IO-NP accumulate in tumours, predominantly in the tumour ECM, following intravenous injection into a murine model of pancreatic neuroendocrine tumour (PNET). In contrast, a control untargeted IO-NP consistently show poor tumour uptake, and IO-NP conjugated to a pentapeptide. CREKA that bind fibrin clots in blood vessels show restricted uptake in the angiogenic vessels of the tumours. CSG-IO-NP show three-fold higher intratumoral accumulation compared to CREKA-IO-NP. Magnetic resonance imaging (MRI) T₂-weighted scans and T₂ relaxation times indicate significant uptake of CSG-IO-NP irrespective of tumour size, whereas the uptake of CREKA-IO-NP is only consistent in small tumours of less than 3 mm in diameter. Larger tumours with significantly reduced tumour blood vessels show a lack of CREKA-IO-NP uptake. Our data suggest CSG-IO-NP are particularly useful for detecting stroma in early and advanced solid tumours.

By mapping the mechanical properties of tissue, elastography can improve identification of breast cancer. On the macro-scale, ultrasound elastography and magnetic resonance elastography have emerged as effective clinical methods for the diagnosis of tumors. On the micro-scale, optical coherence elastography (OCE) shows promise for intraoperative tumor margin assessment during breast-conserving surgery. Whilst several OCE studies have demonstrated strong potential, the mechanical models used require the assumption of uniaxial stress throughout the sample. However, breast tissue is heterogeneous and contains compressible features ( e . g ., ducts and blood vessels) and collagen-rich fibrotic features ( e . g ., stroma). This heterogeneity can invalidate the assumption of uniaxial stress and reduce the accuracy of OCE, often making it challenging to interpret images. Here, we demonstrate a new variant of OCE based on mapping the Euler angle, i . e ., the angle between the principal compression and the loading axis induced by tissue heterogeneity, which removes the assumption of uniaxial deformation. This is enabled by a hybrid three-dimensional (3-D) displacement estimation method that combines phase-sensitive detection and complex cross-correlation, providing access to the 3-D displacement and 3-D strain tensor on the micro-scale. We demonstrate this new OCE technique through experiments on phantoms and 10 fresh human breast specimens. Through close correspondence with histology, our results show that mapping the Euler angle provides additional contrast to both optical coherence tomography and a current OCE technique in identifying cancer. Mapping the Euler angle in breast tissue may provide a new biomarker for intraoperative tumor margin assessment.