A novel method for evaluating the depletion of veterinary pharmaceuticals using radioisotopes

Antimicrobial resistance (AMR) as one of the world's most pressing public health problems needs immediate attention, because it has the ability to affect the human healthcare, agriculture, and veterinary industries. Despite warnings about overuse and their implications, antimicrobials are overprescribed worldwide for humans and animals, which leads to the promotion of resistant microorganisms such as bacteria. Food is a medium for exposure to or transfer of residues of the drugs and can contribute to the burden of the pharmaceuticals associated with development of AMR. Studying on residues of veterinary drugs in foods is essential in the fight against AMR. Herein, we introduce a new method for visualizing the residues of a veterinary drug in animal matrices using radionuclides, called "Depletion Imaging". Amoxicillin was chosen to be the first antimicrobial for this study. The drug was labeled with [Zn-62/Zn-65] ZnCl2. Radiolabelled amoxicillin and non-labeled amoxicillin were administrated to rainbow trout fish simultaneously. To enable visualization of the remaining residues of amoxicillin in fish, In-vivo positron emission tomography (PET) imaging was done at different intervals from 30 min to 21 days after administration. Evaluation of the amount of radiolabelled amoxicillin in fish was done using a high purity germanium (HPGe) nuclear detector, and enzyme linked immunosorbent assay (ELISA) technique was used for the non-labeled drug. In this study, a comprehensive method for in-house production of zinc radioisotopes was also included. The results showed that depletion imaging and biodistribution study based on gamma spectroscopy of radionuclides in tissues, is a precise method for accurate understanding of the drug's distribution, metabolic and excretory profile.