Hyperbranched Polymeric 19F MRI Contrast Agents with Long T2 Relaxation Time Based on β-Cyclodextrin and Phosphorycholine

19F magnetic resonance imaging (19F MRI) is gaining attention as an emerging diagnostic technology. Effective 19F MRI contrast agents (CAs) for in vivo applications require a long transverse (or spin–spin) relaxation time (T2), short longitudinal (or spin–lattice) relaxation time (T1), high fluorine content, and excellent biocompatibility. Here, we present a novel hyperbranched polymeric 19F MRI CA based on β-cyclodextrin and phosphorylcholine. The influence of the branching degree and fluorine content on T2 was thoroughly investigated. Results demonstrated a maximum fluorine content of 11.85% and a T2 of 612 ms. This hyperbranched polymeric 19F MRI CA exhibited both great biocompatibility against cells and organs of mice and high-performance imaging capabilities both in vitro and in vivo. The research provides positive insights into the synthesis strategies, topological design, and selection of fluorine tags for 19F MRI CAs.