Combined SLO-OCT for non-surgical cancer nano-theranostics.

Abstract

Purpose : To evaluate multimodal, cellular-resolution ocular imaging tools for longitudinal investigation of successful xenograft of GFP tagged cancer cells in mouse eye and associated nano-theranostics. Clinical metastasis of solid tumors to the uvea is not uncommon, and so uvea/subretinal xenograft implants, both orthotopic and not orthotopic, have potential clinical relevance.

Methods : Xenografts were created between the uvea and retina in young adult nude (Nu/Nu) mice eyes by injection of different lines of tumor cells. A custom built combined SLO-OCT was used for tracking changes in tumor by its total volume (OCT) and by quantifying Fluorescent signal from GFP labeled Tumor cells (SLO). Consistent correlation was obtained (shown in Figs. 1 (a)-(c)) between both modalities (i.e., OCT and SLO) as the charatersitcs matches. Evolution of neovascularization was studied by OCT angiography (OCTA) for optimal delivery of nanoparticles during tumor growth. To visualize and photo-manipulate nanoparticle delivery to the xenografts, we used multifunctional porphyrin-based micellar nanoplatform as the model system.

Results : The growth of a representative xenograft glioblastoma are shown in Fig 2. This mouse was investigated for over 2 months after glioblastoma injection. SLO and OCT data were acquired simultaneously during imaging sessions and gave complementary information about tumor growth status. The SLO fluorescence channel allows monitoring of position and relative number of GFP-labeled glioblastoma cells, while the OCT data provided tumor volume measurement. Pv-OCTA was used to map the local vasculature, including neovascularization arising from the retina and choroid. Doxorubicin loaded nanoporphirin was delivered and activated from 84th day after injection.

Conclusions : Combined SLO/OCT imaging can provide in vivo cellular-level information about tumor development after initial injection, about nanocarrier distribution within the tumor microenvironment, and about tumor response to controlled optically activated treatment. This information will enable us to maximize the potential of light-stimulated nanotheranostic agents.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Fig. 1: Correlation between tumor growth parameters extracted by SLO and OCT for tumors with different growth rates.

 

Fig. 2: Growth and successful treatment of cancerous xenograft tumor.