%0 Journal Article
%T Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes
%A A. Marissa Wolfe
%A Anjan Motamarry
%A Ayele H. Negussie
%A Bradford J. Wood
%A Christian Rossmann
%A Dieter Haemmerich
%A James Small
%J International Journal of Hyperthermia
%D 2019
%R https://doi.org/10.1080/02656736.2019.1642521
%X Abstract Objective: Thermosensitive liposomal doxorubicin (TSL¨CDox) is a promising stimuli-responsive nanoparticle drug delivery system that rapidly releases the contained drug in response to hyperthermia (HT) (>40£¿¡ãC). Combined with localized heating, TSL¨CDox allows highly localized delivery. The goals of this study were to demonstrate that real-time fluorescence imaging can visualize drug uptake during delivery, and can predict tumor drug uptake. Methods: Nude mice carrying subcutaneous tumors (Lewis lung carcinoma) were anesthetized and injected with TSL¨CDox (5£¿mg/kg dose). Localized HT was induced by heating tumors for 15, 30 or 60£¿min via a custom-designed HT probe placed superficially at the tumor location. In vivo fluorescence imaging (excitation 523£¿nm, emission 610£¿nm) was performed before, during, and for 5£¿min following HT. After imaging, tumors were extracted, drug uptake was quantified by high-performance liquid chromatography, and correlated with in vivo fluorescence. Plasma samples were obtained before and after HT to measure TSL¨CDox pharmacokinetics. Results: Local drug uptake could be visualized in real-time during HT. Compared to unheated control tumors, fluorescence of heated tumors increased by 4.6-fold (15£¿min HT), 9.3-fold (30£¿min HT), and 13.2-fold (60£¿min HT). HT duration predicted tumor drug uptake (p£¿=£¿.02), with tumor drug concentrations of 4.2£¿¡À£¿1.3£¿¦Ìg/g (no HT), 7.1£¿¡À£¿5.9£¿¦Ìg/g (15£¿min HT), 14.1£¿¡À£¿6.7£¿¦Ìg/g (30£¿min HT) and 21.4£¿¡À£¿12.6£¿¦Ìg/g (60£¿min HT). There was good correlation (R2£¿=£¿0.67) between fluorescence of the tumor region and tumor drug uptake. Conclusions: Real-time in vivo fluorescence imaging can visualize drug uptake during delivery, and can predict tumor drug uptake
%U https://www.tandfonline.com/doi/full/10.1080/02656736.2019.1642521