Synthesis and Bioimaging of Positron-Emitting 15O-Labeled 2-Deoxy-D-glucose of Two-Minute Half-Life

In positron emission tomography (PET), which exploits the affinity of a radiopharmaceutical for the target organ, a systematic repertoire of oxygen‐15‐labeled PET tracers is expected to be useful for bioimaging owing to the ubiquity of oxygen atoms in organic compounds. However, because of the 2‐min half‐life of 15O, the synthesis of complex biologically active 15O‐labeled organic molecules has not yet been achieved. A state‐of‐the‐art synthesis now makes available an 15O‐labeled complex organic molecule, 6‐[15O]‐2‐deoxy‐D‐glucose. Ultrarapid radical hydroxylation of 2,6‐dideoxy‐6‐iodo‐D‐glucose with molecular oxygen labeled with 15O of two‐minute half‐life provided the target 15O‐labeled molecule. The labeling reaction with 15O was complete in 1.3 min, and the entire operation time starting from the generation of 15O‐containing dioxygen by a cyclotron to the purification of the labeled sugar was 7 min. The labeled sugar accumulated in the metabolically active organs as well as in the bladder of mice and rats. 15O‐labeling offers the possibility of repetitive scanning and the use of multiple PET tracers in the same body within a short time, and hence should significantly expand the scope of PET studies of small animals. My PET nuclide: 6‐[15O]‐2‐Deoxy‐D‐glucose can be made by ultrarapid radical hydroxylation of 2,6‐dideoxy‐6‐iodo‐D‐glucose with 15O‐labeled molecular oxygen. It is by far the most‐complex 15O‐labeled compound produced to date. This extremely short‐lived organic tracer of two‐minute half‐life was applied to positron emission imaging of small animals.