Synthesis and Acute Toxicity Evaluation of FEONM: A Novel PET Imaging Precursor for Alzheimer's Disease

Background Alzheimer’s disease (AD) remains a major global health challenge, necessitating the development of more effective diagnostic tools. This study focuses on the development and evaluation of FEONM, a novel PET imaging precursor structurally derived from FDDNP, designed for potential use in AD imaging. To assess its suitability for clinical translation, both synthetic feasibility and safety profile were examined. A practical multi-step synthetic route was established using Bucherer and Knoevenagel reactions. Additionally, the acute toxicity of FEONM was evaluated in Sprague-Dawley rats (n = 5 per group per sex) following administration at 0.2, 1.0, and 5.0 mg/kg doses. Key toxicological endpoints included body weight monitoring, hematological and clinical chemistry analysis, and gross necropsy findings. Results No mortality or abnormal clinical signs were observed across all dose groups. Low and moderate doses did not affect normal growth, while 5.0 mg/kg caused temporary weight suppression. Dose-dependent hematological and biochemical effects showed sex-specific differences, with females displaying greater hematological sensitivity including significant lymphocyte reduction (68% vs 30% in males) at the highest dose. Males exhibited notable glucose elevation (22%) and electrolyte disturbances. Gross necropsy revealed hepatic and mild gastrointestinal changes only at 5.0 mg/kg in 20% of animals, indicating a clear threshold effect with no pathological lesions at lower doses. Conclusions FEONM was successfully synthesized and showed acceptable safety margins at clinically relevant doses. The NOAEL was determined to be 1.0 mg/kg. Different toxicity effects were observed between male and female rats, with females being more sensitive to blood-related changes and males showing more metabolic problems. These results indicate that FEONM has potential for clinical use, but additional long-term studies are needed to determine the optimal dosing for safe human application.