A Bioorthogonal Probe for Multiscale Imaging by (19)F-MRI and Raman Microscopy: From Whole Body to Single Cells

[Image: see text] Molecular imaging techniques are essential tools for better investigating biological processes and detecting disease biomarkers with improvement of both diagnosis and therapy monitoring. Often, a single imaging technique is not sufficient to obtain comprehensive information at different levels. Multimodal diagnostic probes are key tools to enable imaging across multiple scales. The direct registration of in vivo imaging markers with ex vivo imaging at the cellular level with a single probe is still challenging. Fluorinated ((19)F) probes have been increasingly showing promising potentialities for in vivo cell tracking by (19)F-MRI. Here we present the unique features of a bioorthogonal (19)F-probe that enables direct signal correlation of MRI with Raman imaging. In particular, we reveal the ability of PERFECTA, a superfluorinated molecule, to exhibit a remarkable intense Raman signal distinct from cell and tissue fingerprints. Therefore, PERFECTA combines in a single molecule excellent characteristics for both macroscopic in vivo(19)F-MRI, across the whole body, and microscopic imaging at tissue and cellular levels by Raman imaging.