There is a pressing need for techniques that can be used for the noninvasive assessment of response to therapy and staging of disease. As many pathological conditions are associated with disordered glucose metabolism, such as diabetes, stroke and cancer, Simon Walker-Samuel and his colleagues have developed a noninvasive MRI-based method for imaging glucose uptake in vivo termed glucose chemical exchange saturation transfer (glucoCEST). This potentially cost-effective approach does not require the use of radiolabeled glucose analogs or ionizing radiation and allows nonlabeled glucose to be imaged at physiological quantities. Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. We developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between hydroxyl groups and water. This method differs from existing molecular imaging methods because it permits detection of the delivery and uptake of a metabolically active compound in physiological quantities. We show that our technique, named glucose chemical exchange saturation transfer (glucoCEST), is sensitive to tumor glucose accumulation in colorectal tumor models and can distinguish tumor types with differing metabolic characteristics and pathophysiologies. The results of this study suggest that glucoCEST has potential as a useful and cost-effective method for characterizing disease and assessing response to therapy in the clinic.

Introduction: Aggregation of tau is a hallmark of many neurodegenerative diseases, and tau imaging with positron emission tomography (PET) may allow early diagnosis and treatment monitoring. We assessed binding of the PET tracer [¹⁸F]AV‐1451 in a range of dementias.Methods: Phosphorimaging was used to quantify binding to postmortem brain tissue from 33 patients with different, histopathologically characterized, neurodegenerative dementias.Results: [¹⁸F]AV‐1451 showed high specific binding in cases with Alzheimer's disease (AD), moderate binding in Pick's disease and frontotemporal dementia with parkinsonism‐17, and low but displaceable binding in corticobasal degeneration, progressive supranuclear palsy, non–tau proteinopathies, and in controls without pathology. Tracer binding did not correlate with tau load within disease groups.Discussion: [¹⁸F]AV‐1451 binds to tau in AD, and some other tauopathies. However, evidence for a non–tau binding site and lack of correlation between tracer binding and antibody staining suggest that reliable quantification of tau load with this tracer is problematic.

Of the molecular biochemical alterations that occur during apoptosis, activation of caspases, notably caspase-3, is probably the most attractive for developing specific in vivo molecular imaging probes. We recently designed a library of isatin-5 sulfonamides and selected [ ¹⁸ F]ICMT-11 for further evaluation on the basis of subnanomolar affinity for activated capsase-3, high metabolic stability, and facile radiolabeling. In this present study, we have demonstrated that [ ¹⁸ F]ICMT-11 binds to a range of drug-induced apoptotic cancer cells in vitro and to 38C13 murine lymphoma xenografts in vivo by up to 2-fold at 24 h posttreatment compared to vehicle treatment. We further demonstrated that the increased signal intensity in tumors after drug treatment, detected by whole body in vivo microPET imaging, was associated with increased apoptosis. In summary, we have characterized [ ¹⁸ F]ICMT-11 as a caspase-3/7 specific PET imaging radiotracer for the assessment of tumor apoptosis that could find utility in anticancer drug development and the monitoring of early responses to therapy.

A novel [¹⁸F]NF reagent and two novel radiochemical transformations have been developed: [¹⁸F]NFSi has been prepared from sodium dibenzenesulfonimide and reacted in the presence of silyl enol ethers and allylsilanes to deliver labelled fluorinated ketones and allylic fluorides respectively; the radiosynthesis of the fluorinated A ring of vitamin D₃ has also been completed with success.