Abstract Photoacoustics (PA) is a hybrid in vivo imaging modality that combines the temporal resolution of optics, and low acoustic scattering and high spatial resolution of micro-ultrasound. This innovation can discern optical absorption of endogenous and exogenous contrast agent(s) in the tumor micro-environment. This advancement is made possible by precise control of optical wavelength using a tunable pulsed laser, ranging from 680-970nm. In this study, we demonstrate fluorescent pyroporphysome, a nanoparticle, to be a photoacoustic contrast agent by which we can monitor its accumulation locally within the tumor. Approach: Co-registered ultrasound (anatomical) and PA imaging of subcutaneous tumors was accomplished with a LZ250 21 MHz transducer on the Vevo® LAZR system (FUJIFILM VisualSonics, Inc.). Mammary tumors were generated by implanting from MDA-MB-231H2N cell line under the skin line. Pyroporphysomes (120 nm in size) were administered by tail vein at a dose of 300 nmoles. Multiwavelength photoacoustic scans were acquired and quantified over 24 hours using Vevo Spectro (FUJIFILM VisualSonics, Inc.), an ensuite absorbance spectrum quantification tool. Cri Maestro (Quorum Technologies, Inc.) was used for concurrent whole body fluorescence imaging. Results: Multi-wavelength analyses identified an in vivo PA absorbance of 680 nm to pyroporphysome. Earliest detection was at 20 minutes post bolus in the tumor and PA signal for pyroporphysomes persisted at 24 h. Signal accumulation is supported by a 22 fold change in signal intensity per 3D volume (3.8% post bolus vs 87% at 24h). Fluorescence analyses validate this accumulation in the tumor. Taken together, photoacoustic imaging identifies pyroporphysome as a bimodal contrast agent. Additional evidence includes a shift in signal localization in the PA scans wherein pyroporphysomes were first detected at the tumor periphery (<1mm below the skin line), and as deep as 2mm towards the tumor core at 24 hours. In conclusion, data herein presents photoacoustic imaging as the next generation imaging modality for concurrent molecular and anatomical information to better understand mechanistic changes in the tumor microenvironment. Citation Format: Minalini Lakshman, James Bu, Azusa Maeda, Gang Zheng, Andrew Needles, Catherine Theodoropoulos, Ralph Da Costa. A validation study on photoacoustics imaging of fluorescent pyroporphysome in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 720. doi:10.1158/1538-7445.AM2013-720
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