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Refining a Large Animal Model Assessing Real-Time Lymphatic Function: Getting Closer to Clinical Translation
Valeria P Bustos1, Rosie Friedman1, James E Fanning1, Jason Dinh2, Hajin Joanne Kim2, Rita Laurence2, Satoshi Kashiwagi2, Bernard T Lee1, HakSoo Choi2, Dhruv Singhal1 1Division of Plastic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 2Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA

Background: Developing a method to evaluate real-time lymphatic function will have profound implications for the diagnosis, surveillance, and treatment of lymphatic diseases. Currently, no accurate and reproducible method of measuring direct lymphatic flow exists. Our team has been working on a large animal model to develop a method for evaluating real-time lymphatic function utilizing optical dyes. We will present our most recent modifications aimed at delivering a model which is clinically translatable.

Methods: Two optical dyes were injected into the respective hind limbs of nine female swine, and their transit was simultaneously assessed. Specifically, near-infrared imaging of blood and urine samples was performed after subcutaneous injection of 700 nm and 800 nm emitting fluorophores at set time points. Continuous imaging was also performed of the superficial epigastric vein and adjacent skin. The pharmacokinetics, biodistribution, and clearance of the two dyes were evaluated.

Results: Inconsistent pharmacokinetics of the two dyes led to refinement in both fluorophore delivery and composition. Reproducible fluorophore delivery into the dermis was achieved utilizing a novel delivery platform VAX-ID that provides standardized, accurate, and user-friendly intradermal injections. Moreover, we modified our fluorophore by removing human serum albumin, thereby optimizing the pharmacokinetics of the optical dye for ultimate clinical translation.

Conclusion: Developing a model for noninvasive measures of direct lymphatic flow in real-time remains a critical unmet need in the field of lymphatics. We continue to focus on the clinical translatability of our model with the goal of human translation in the near future.
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