A magnetic resonance approach is presented that enables high-sensitivity, high-contrast molecular imaging by exploiting xenon biosensors. These sensors link xenon atoms to specific biomolecular targets, coupling the high sensitivity of hyperpolarized nuclei with the specificity of biochemical interactions. We demonstrated spatial resolution of a specific target protein in vitro at micromolar concentration, with a readout scheme that reduces the required acquisition time by >3300-fold relative to direct detection. This technique uses the signal of free hyperpolarized xenon to dramatically amplify the sensor signal via chemical exchange saturation transfer (CEST). Because it is ∼10,000 times more sensitive than previous CEST methods and other molecular magnetic resonance imaging techniques, it marks a critical step toward the application of xenon biosensors as selective contrast agents in biomedical applications.

Significance: The field of xenon magnetic resonance imaging (MRI) is moving closer to the development of targeted xenon biosensors for in vivo applications. It is motivated by aca.10⁸-fold improved sensitivity compared with conventional proton MRI. This has been enabled by significant improvements to hardware (xenon polarizer design) and sensitivity (through the hyperpolarized¹²⁹Xe chemical exchange saturation transfer technique). In this paper, we capitalize on these improvements by demonstrating targeted xenon imaging on cells using a modular xenon biosensor. With this method, we can detect target cells with as little as 20 nM of our xenon contrast agent. Imaging of such low levels of cell-specific xenon hosts is unprecedented and reinforces the potential of xenon–cryptophane biosensors for molecular imaging applications.

Cancer-related cachexia is an obscure syndrome leading to muscle wasting, reduced physical fitness and quality of life. The aim of this study was to assess morphology, metabolism, and microcirculation in skeletal muscles of patients with cancer-related cachexia and to compare these data with matched healthy volunteers. In 19 patients with cancer-induced cachexia and 19 age-, gender-, and body-height-matched healthy volunteers body composition and aerobic capacity (VO(2max)) were analyzed. Skeletal muscle fiber size and capillarization were evaluated in biopsies of the vastus lateralis muscle. The cross-sectional area (CSA) of the quadriceps femoris muscle was measured by magnetic resonance imaging as well as its isokinetic and isometric force. The energy and lipid metabolism of the vastus lateralis muscle was quantified by (31)P and (1)H spectroscopy and parameters of its microcirculation by contrast-enhanced ultrasonography (CEUS). Morphologic parameters were about 30% lower in cachexia than in volunteers (body mass index: 20 +/- 3 vs. 27 +/- 4 kg m(-2), CSA: 45 +/- 13 vs. 67 +/- 14 cm(2), total fiber size: 2854 +/- 1112 vs. 4181 +/- 1461 microm(2)). VO(2max) was reduced in cachexia (23 +/- 9 vs. 32 +/- 7 ml min(-1) kg(-1), p=0.03), whereas histologically determined capillary density and microcirculation in vivo were not different. Both concentrations of muscular energy metabolites, pH, and trimethyl-ammonium-containing compounds were comparable in both groups. Absolute strength of quadriceps muscle was reduced in cachexia (isometric: 107 +/- 40 vs. 160 +/- 40 Nm, isokinetic: 101 +/- 46 vs. 167 +/- 50 Nm; p=0.03), but identical when normalized on CSA (isometric: 2.4 +/- 0.5 vs. 2.4 +/- 0.4 Nm cm(-2), isokinetic: 2.2 +/- 0.4 vs. 2.5 +/- 0.5 Nm cm(-2)). Cancer-related cachexia is associated with a loss of muscle volume but not of functionality, which can be a rationale for muscle training.