Spectrally Resolved Magnetic Resonance Imaging of the Xenon Biosensor** Christian Hilty,* Thomas J. Lowery, David E. Wemmer, and Alexander Pines Dr. C. Hilty, Prof. A. Pines Lawrence Berkeley National Laboratory, Materials Sciences Division, and University of California Berkeley, Department of Chemistry, Berkeley CA 94720, USA Fax: +1 (510) 486 5744 E-mail: hilty@berkeley.edu T. Lowery, Prof. D. Wemmer Lawrence Berkeley National Laboratory, Physical Biosciences Division, and University of California Berkeley, Department of Chemistry, Berkeley CA 94720, USA [**] This work was supported by the Director, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division, of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098. C.H. acknowledges support from the Schweizerischer Nationalfonds through a post-doctoral fellowship. T.L. acknowledges support from the University of California Biotechnology Research and Education Program for a training grant. Due to its ability to non-invasively record images, as well as elucidate molecular structure, nuclear magnetic resonance is the method of choice for applications as widespread as chemical analysis and medical diagnostics. Its detection threshold is, however, limited by the small polarization of nuclear spins in even the highest available magnetic fields. This limitation can, under certain circumstances, be alleviated by using hyper-polarized substances. [1] Xenon biosensors make use of the sensitivity gain of hyperpolarized xenon to provide magnetic resonance detection capability for a specific low-concentration target. [2-4] They consist of a cryptophane cage, [5] which binds one xenon atom, and which has been connected via a linker to a targeting moiety such as a ligand or antibody. Recent work has shown the possibility of using the xenon biosensor to detect small amounts of a substance in a heterogeneous environment by NMR. [6] Here, we demonstrate that magnetic resonance (MR) provides the capability to obtain spectrally and spatially resolved images of the distribution of