Directional sensor for radioluminescence microscopy of next-generation tumor models - Microphysiological tumor models (μPTM) are increasingly used for preclinical research due to their ability to
closely simulate, in vitro, the physiology of solid tumors. With the advent of microfluidics technology, new
methods have been introduced to grow tissues in 3D inside perfused chambers and precisely control biological
factors, such as cells, nutrients and oxygen, at a spatial and temporal level. These models can incorporate 3D
extracellular matrices (ECM) and perfusable neovasculature, both key components of solid tumors. Being
optically transparent, they permit excellent visualization of live cells through advanced optical microscopy
techniques.
Radioluminescence microscopy (RLM) is a method that was developed to image clinical radiotracers in live
cells with high spatial resolution. However, this method in its current form cannot be used to adequately image
3D cell cultures due to the loss of spatial resolution and lack of tomographic capabilities for imaging thick
samples. The goal of this project is to develop a novel layered scintillator design for limited-angle tomographic
imaging of 3D cell cultures and other in vitro tissues such as organoids and tumor-chips. The dual-layer
scintillator will provide angular information that can be used for 3D reconstruction of radiotracer distribution in
these thick samples. Thus, such a technological advance has the potential for widespread use in research and
medicine using the arsenal of existing diagnostic and therapeutic radioisotopes. It could be used to bridge the
gap between these emergent tumor models and clinical trials, which use PET biomarkers as disease endpoints.
In addition, the technology could be used to characterize how properties specific to the 3D microenvironment
surrounding microtumors could affect the uptake and retention of radiotracers. Higher spatial resolution will allow
cells to be probed in situ, in dense tissue sections. These new capabilities will be critical to help researchers
develop patient-derived tumor models that recapitulate the most salient features of solid tumors and can be
imaged using clinically relevant PET tracers.
The objective of this Phase I project is to demonstrate the feasibility of successfully fabricating thin layers of
a highly dense transparent scintillator, separated by a layer of non-scintillating transparent material. This novel
design enables visualization of two scintillation spots so that the angle of incidence can be estimated to provide
limited-angle tomographic projections. This innovative design will provide the spatial resolution required for
visualization of radiotracer uptake in 3D cell cultures, microtumors, and other thick specimens.
