Dopamine D2 Receptor Radiopharmaceutical: I-123-Epidepride Toxicology and Preclinical SPECT Image

Dopamine plays an important role in the brain, and several diseases of the central nervous system are associated with dopamine system dysfunction. A significantly different density of dopamine D2 receptors has been reported in Parkinson’s disease patients. Dopamine D2 receptor distribution in the central nervous system can be evaluated using the radiopharmaceutical [123I]Epidepride, which shows great potential for use as an imaging agent. In the image analysis software showed that the binding ratios of [123I]Epidepride significantly useful alterations of dopamine D2/D3 receptor binding sites in striatum, hypothalamus and midbrain. To investigate the toxicity of this radiopharmaceutical, we determined its effects in Sprague Dawley rats. We first synthesized Epidepride for the toxicity study, and then sought to determine the “No Observed Adverse Effect Level” (NOAEL) of Epidepride by analyzing acute single-dose effects. We injected unlabeled Epidepride (0 to 2000 µg/kg) into the tail vein of rats. This dose provided a safety margin of 100- to 10,000-fold over the maximum recommended human dose (200 µg/60 kg). After two weeks, we observed rat mortality, clinical situation (hypoactivity, body weight), and gross necropsy, and there were no changes. This lack of change showed that Epidepride exerted no adverse toxic effects in our rat model at dosage levels up to 2000 µg/kg. The results can achieve suitable be a reference method in toxicology and in vivo image for new drug studies of dopamine D2/D3 receptor related disease like schizophrenia and Parkinson’s syndrome to helpful evaluate therapeutic effects in the future.