Radioactivity in the darkroom: the role of radioluminescence microscopy in PET radiotracer characterization and development (Conference Presentation)

Abstract

With 2500 scanners installed and 2 million scans performed last year in the United States, positron emission tomography (PET) has emerged as one of the most important imaging tools in oncology. The widespread availability of PET imaging and radiochemistry facilities has stirred the development of new PET tracers. The current pipeline for radiotracer development uses analytical tools that assume that the targeted cell populations are homogeneous. For instance, in vivo imaging tests reduce results to a single quantitative metrics, the standardized uptake value, which represents the average behavior of millions of cells. In reality, tumors and other organs are formed by clonally heterogeneous collections of different cell types; the average of these cells is not necessarily representative of the individual cells that make up the population. To give an example, the PET signal measured in a tumor is often ascribed to cancer cells alone when in fact other cell types such as immune cells and stromal cell contribute significantly to the average signal. These considerations have led to the development of a novel method, radioluminescence microscopy (RLM), that can characterize radiotracer uptake heterogeneity at the level of single cells. RLM combines optical and ionizing radiation to yield high-resolution microscopic images of cells and their interactions with radiotracers. The fundamental principles of RLM will be explained and its application to radiotracer discovery and validation will be presented.