Biodistribution and residue depletion monitoring of 65Zn-labeled sulfadiazine in rainbow trout using PET imaging and HPGe gamma spectroscopy

Monitoring veterinary drug residues in aquaculture is essential for food safety, regulatory compliance, and the determination of reliable withdrawal periods. Sulfadiazine remains one of the therapeutically relevant antibiotics in fish farming, yet characterization of its long-term depletion kinetics in edible tissues is often limited by the sensitivity of conventional analytical methods and by the high cost and synthetic complexity of classical radiotracers such as carbon-14. To address these limitations, the present study employed zinc-65, a relatively cost-effective radionuclide that can be produced in cyclotron facilities available in many countries, to label sulfadiazine and investigate its long-term biodistribution and residue depletion profile in rainbow trout ( Oncorhynchus mykiss ). Following co-administration of the zinc-65-labeled sulfadiazine complex and the unlabeled drug, biodistribution studies and whole-body PET imaging were performed at selected time points over an 8-week period to visualize spatial and temporal tracer distribution. After imaging, the fish were sacrificed and dissected, and samples of fillet with skin, internal organs, and other tissues were collected for quantitative analysis using high-purity germanium (HPGe) gamma spectroscopy. This combined imaging and tissue-based radioanalytical approach enabled sensitive tracking of sulfadiazine-associated radiolabeled residues and provided both spatial and quantitative information on their persistence and clearance. The results demonstrated successful PET visualization and biodistribution monitoring throughout the 8-week study period, while HPGe measurements confirmed the gradual depletion and trace persistence of radiolabeled residues in edible fillet tissue and other organs. By using zinc-65 as an economically more accessible alternative to carbon-14, with the additional advantage of domestic cyclotron production, this integrated PET/HPGe methodology provides a sensitive and practical platform for studying long-term veterinary drug kinetics and may support improved residue evaluation and withdrawal-time assessment in aquaculture.