This study investigated the application of VivoVist™, a high-contrast micro-CT contrast agent, in spectral Photon-Counting (PC) micro-CT imaging in mouse models. With a long blood half-life, superior concentration, and reduced toxicity VivoVist, composed of barium (Ba)-based nanoparticles, offers a cost-effective solution for enhancing Computed Tomography (CT) imaging. To evaluate its efficacy, we employed an in-house developed spectral micro-CT with a photon-counting detector. VivoVist was administered through retro-orbital injection in a non-tumor-bearing C57BL/6 mouse and in two mice with MOC2 buccal tumors, with scans taken at various post-injection intervals. We used a multi-channel iterative reconstruction algorithm to provide multi-energy tomographic images with a voxel size of 125 microns or 75 microns for high-resolution scans; we performed post-reconstruction spectral decomposition with water, calcium (Ca), iodine (I), and barium (Ba) as bases. Our results revealed effective separation of Ba from I-based contrast agents with minimal cross-contamination and superior contrast enhancement for VivoVist at 39 keV. We also observed VivoVist's potential in delineating vasculature in the brain and its decreasing concentration in the blood over time post-injection, with increased uptake in the liver and spleen. We also explored the simultaneous use of VivoVist and liposomal iodinated nanoparticles in a cancer study involving radiation therapy. Our findings reveal that VivoVist, combined with radiation therapy, did not significantly increase liposomal iodine accumulation within head and neck squamous cell carcinoma tumors. In conclusion, our work confirms VivoVist's promising role in enhancing PCCT imaging and its potential in studying combination therapy, warranting further investigation into its applications in diagnostics and radiotherapy.
Significance: Decreasing the oxygen consumption rate (OCR) of tumor cells is a powerful method for ameliorating tumor hypoxia. However, quantifying the change in OCR is challenging in complex experimental systems.
Aim: We present a method for quantifying the OCR of two tumor cell lines using oxygen-sensitive dual-emissive boron nanoparticles (BNPs). We hypothesize that our BNP results are equivalent to the standard Seahorse assay.
Approach: We quantified the spectral emissions of the BNP and accounted for external oxygen diffusion to quantify OCR over 24 h. The BNP-computed OCR of two breast cancer cell lines, E0771 and 4T07, were compared with their respective Seahorse assays. Both cell lines were also irradiated to quantify radiation-induced changes in the OCR.
Results: Using a Bland–Altman analysis, our BNPs OCR was equivalent to the standard Seahorse assay. Moreover, in an additional experiment in which we irradiated the cells at their 50% survival fraction, the BNPs were sensitive enough to quantify 24% reduction in OCR after irradiation.
Conclusions: Our results conclude that the BNPs are a viable alternative to the Seahorse assay for quantifying the OCR in cells. The Bland–Altman analysis showed that these two methods result in equivalent OCR measurements. Future studies will extend the OCR measurements to complex systems including 3D cultures and in vivo models, in which OCR measurements cannot currently be made.
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