Safety Evaluation of 177 Lu-TEFAPI-06 with Long-Term Blood Circulation in Rodents

Purpose To evaluate the pharmacological and toxicological safety of TEFAPI-06 in rodents, offering crucial insights for its clinical trial applications. Methods For bistribution analysis, SD rats were divided into six groups to study the kinetics of ¹⁷⁷ Lu-TEFAPI-06 post intravenous administration. Rats were euthanized at predetermined time points (0.5h, 2h, 24h, 48h, 72h, 144h) for radioactivity measurements in blood and various organs. Additionally, tumor uptake in ¹⁷⁷ Lu-TEFAPI-06 treated mice was monitored using small animal in vivo imaging. For toxicological assessment, SD rats were assigned to high, medium, low-dose, and control groups. A single dose of TEFAPI-06 was administered via the tail vein. Observations included immediate and short-term physiological responses (up to 6h post-dosing), followed by twice-daily general health assessments. Blood samples were collected on days 3 and 15 for comprehensive analysis, including complete blood count, liver and kidney function, glucose and lipid levels, and histopathological evaluations. Results ¹⁷⁷ Lu-TEFAPI-06 is mainly metabolized in the liver and excreted through the kidneys, showing effective tumor targeting and prolonging residence time. Post-dose observations showed no significant behavioral or respiratory changes in any of the groups. The body weight and blood biochemical indexes of routine blood parameters in all dose groups were statistically comparable with those in the control group (P > 0.05). Pathological examination revealed no obvious abnormalities. Conclusion TEFAPI-06 appears safe in SD rats following a single intravenous injection, with efficient tumor targeting and rapid metabolism in normal tissues. These findings support its potential for further clinical trial considerations.