title: Quantitative imaging of disease signatures through radioactive decay signal conversion.
abstract: In the era of personalized medicine, there is an urgent need for in vivo techniques able to sensitively detect and quantify molecular activities. Sensitive imaging of gamma rays is widely used; however, radioactive decay is a physical constant, and its signal is independent of biological interactions. Here, we introduce a framework of previously uncharacterized targeted and activatable probes that are excited by a nuclear decay-derived signal to identify and measure molecular signatures of disease. We accomplished this by using Cerenkov luminescence, the light produced by β-particle-emitting radionuclides such as clinical positron emission tomography (PET) tracers. Disease markers were detected using nanoparticles to produce secondary Cerenkov-induced fluorescence. This approach reduces background signal compared to conventional fluorescence imaging. In addition to tumor identification from a conventional PET scan, we demonstrate the medical utility of our approach by quantitatively determining prognostically relevant enzymatic activity. This technique can be applied to monitor other markers and represents a shift toward activatable nuclear medicine agents.
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Daniel L J
authors.initials: DL
authors.lastname: Thorek
authors.forename: Anuja
authors.initials: A
authors.lastname: Ogirala
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Beattie
authors.forename: Jan
authors.initials: J
authors.lastname: Grimm
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D004194:Disease / Q000145:classification*; D005453:Fluorescence; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D049268:Positron-Emission Tomography; D011868:Radioisotopes
chemical_list: D011868:Radioisotopes; D020778:Matrix Metalloproteinase 2