Abstract 4269: Dynamic contrast-enhanced MSOT imaging to intratumoral pharmacokinetic modeling
Authors: Xiao Ted G. , Samykutty Abhilash , Weis Jared , Gayzik Scott , Topaloglu Umit , Thomas Alexandra , Chiba Akiko , McNally Lacey R. 
Published: August 2018

Introduction: Interactions between biological features and nanoparticles could affect tracer biodistribution, kinetics, clearance, and translocation. Because these effects cannot be simply extrapolated from in vitro studies, in vivo quantitative data are needed to determine the pharmacokinetic properties of tracers. Planar fluorescence or 2D fluorescent /bioluminescence imaging has the potential for the tracers to accumulate outside of the tumor and the potential of light scattering. MSOT allows for more precise determination of signal origin and intensity. HypoxiSense 680 is a tracer that targets the hypoxic tumor environment. Our objective is to assess the pharmacokinetics of HypoxiSense 680 in the context of an orthotopic breast tumor in vivo using MSOT. This study takes advantage of a novel contrast tracking imaging modality to study intratumoral pharmacokinetics in in vivo setting with a hypoxia-targeting tracer. Methods: Female, athymic mice were orthotopically implanted with MDA-MB-231 cells and tumors were allowed to grow to 4mm in diameter prior to the evaluation of the tracer. Mice were anesthetized with isoflurane and a mixture of 0.1L of O2 and 0.9L of medical air prior to the insertion of a tail vein catheter. The mouse was placed into the MSOT scanner for 10 minutes to equilibrate. Once the breast tumor was localized, images were acquired for 5 minutes to obtain a baseline measurement. Subsequently, 100μL of HypoxiSense 680 at the recommended dosage of 2nmol per mouse was injected over the course of 30s followed by a catheter flush with 100μL of saline solution. MSOT inVision 256-TF continuously measured optoacoustic signal within the mouse in vivo for a duration of 25 minutes. HypoxiSense 680 signal was isolated by spectral unmixing using backprojection algorithm. Results: A 2-compartmental PK model was constructed in MATLAB and curve-fitted against the animal data. There were two compartments to account for the contrast within the circulatory system and the tumor microenvironment. Rate constants of the model were determined by fitting the model curve to the experimental MSOT imaging data: kforward=2.76x10-4 sec-1, kreverse=4.73x10-4 sec-1, kelcentral=1.01x10-5 sec-1, kelperipheral=3.18x10-7 sec-1. The goodness of fit was evaluated (R=0.83, RMSE=0.0015). Conclusion: Optoacoustic imaging with MSOT provides live tracking of spectrally unique contrasts in vivo. This capability allows for a novel characterization method of intratumoral drug/contrast kinetics in vivo in mouse tumor models.

Citation Format: Ted G. Xiao, Abhilash Samykutty, Jared Weis, Scott Gayzik, Umit Topaloglu, Alexandra Thomas, Akiko Chiba, Lacey R. McNally. Dynamic contrast-enhanced MSOT imaging to intratumoral pharmacokinetic modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4269.