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Pancreatic ductal adenocarcinoma continues to be one of the most lethal cancers today with an abysmal ~8% 5- year survival rate that has remained relatively constant over time. This is thought to be largely due the desmoplastic stroma in the extracellular matrix of these tumor types, inhibiting both the penetration as well as target engagement of treatments. Here we present a methodology for evaluating a monoclonal antibody’s drug target engagement in the presence of an extracellular matrix remodeling drug using paired-agent imaging principles and a subcutaneous tumor mouse model. 

Pancreatic ductal adenocarcinomas (PDACs) are often treatment resistant, and as such widefield imaging methods for the evaluation of ECM composition are needed. Here we present a method to measure the relative abundance of ECM diffracting components in PDAC samples alongside drug penetration in widefield images. Orthotopic mouse PDAC xenografts are grown and assessment of drug penetration as well as ECM composition is done using co-registration of scanning x-ray diffraction (XRD) and EGFR-specific drug penetration fluorescent widefield images. Preliminary data suggests a strongly negative correlation between abundance of diffracting ECM components and penetration of large drugs in solid tumors. This methodology may be used to provide crucial insights into both drug-development approaches and multi-therapeutic treatment strategies in late stage PDAC patients presenting with ECM desmoplasia. 

This work concerns a fluorescence optical projection tomography system for low scattering tissue, like lymph nodes, with angular-domain rejection of highly scattered photons. In this regime, filtered backprojection (FBP) image reconstruction has been shown to provide reasonable quality images, yet here a comparison of image quality between images obtained by FBP and iterative image reconstruction with a Monte Carlo generated system matrix, demonstrate measurable improvements with the iterative method. Through simulated and experimental phantoms, iterative algorithms consistently outperformed FBP in terms of contrast and spatial resolution. Moreover, when projection number was reduced, in order to reduce total imaging time, iterative reconstruction suppressed artifacts that hampered the performance of FBP reconstruction (structural similarity of the reconstructed images with “truth” was improved from 0.15 ± 1.2 × 10⁻³to 0.66 ± 0.02); and although the system matrix was generated for homogenous optical properties, when heterogeneity (62.98 cm^-1variance inµ_s) was introduced to simulated phantoms, the results were still comparable (structural similarity homo: 0.67 ± 0.02 vs hetero: 0.66 ± 0.02). 

Transmittance and fluorescence optical projection tomography can offer high-resolution and high-contrast visualization of whole biological specimens; however, applications are limited to samples exhibiting minimal light scattering. Our previous work demonstrated that angular-domain techniques permitted imaging of $\sim <\#comment/>1\mathrm{c}\mathrm{m}$diameter noncleared lymph nodes because of their low scattering nature. Here, an angle-restricted transmittance/fluorescence system is presented and characterized in terms of geometric and fluorescence concentration reconstruction accuracy as well as spatial resolution, depth of focus, and fluorescence limits of detection. Using lymph node mimicking phantoms, results demonstrated promising detection and localization capabilities relevant for clinical lymph node applications.