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This study aimed to develop a method of administering F-18-FDG to the common octopus in order to perform a PET biodistribution assay characterizing glucose metabolism in organs and regenerating tissues. Methods: Seven animals (two of which had a regenerating arm) were anesthetized with 3.7% MgCl2 in artificial seawater and then injected with 18-30 MBq of isosmotic F-18-FDG through either the left branchial heart or the anterior vena cava. After an uptake time of about 50 min, the animals were sacrificed and placed on the bed of a small-animal PET scanner, and 10-min static acquisitions were obtained at 3-4 bed positions to visualize the entire body. To confirm image interpretation, internal organs of interest were collected and counted with a.-counter. Results: Administration through the anterior vena cava resulted in a good full-body distribution of F-18-FDG as seen on the PET images. Uptake was high in the mantle mass and relatively lower in the arms. In particular, the brain, optic lobes, and arms were clearly identified and were measured for their uptake (SUVmax: 6.57 +/- 1.86, 7.59 +/- 1.66, and 1.12 +/- 0.06, respectively). Interestingly, F-18-FDG uptake was up to 3-fold higher in the highly proliferating areas of regenerating arms. Conclusion: This study represents a stepping-stone to the use of non-invasive functional techniques for addressing questions about invertebrate neuroscience and regenerative medicine.