Safety, Biodistribution, and Dosimetry of 99mTc-HYNIC-Annexin V, a Novel Human Recombinant Annexin V for Human Application

99mTc-hydrazinonicotinamido (HYNIC)-annexin V is a novel tracer for in vivo imaging of apoptosis. The present study on humans was performed to investigate the safety of 99m Tc-HYNIC-annexin V and to quantify the biodistribution and radiation dose. Methods: Six healthy, male volunteers participated in the study. A dual-head gamma camera was used to acquire conjugate anterior and posterior views. Imaging started with a transmission scan using a 57 Co-flood source to obtain a map of the local thickness of the volunteer. Approximately 250 MBq of 99m Tc-HYNIC-annexin V were injected intravenously, directly followed by a 30-min dynamic study. Whole-body scans were obtained at about 30 min, 3 h, 6 h, and 24 h after injection. Organ uptake was determined after correction for background, scatter, and attenuation. The MIRDOSE3.1 program was used to calculate organ-absorbed doses and effective dose. Signs of adverse effects were investigated by monitoring renal and liver function, hematology, blood coagulation, and vital signs (blood pressure, pulse, respiration rate, temperature, and electrocardiogram). Results: The kidneys accumulated 49.7 ± 8.1 percentage injected dose (%ID) at 3 h after injection; the liver, 13.1 ± 1.0 %lD; the red marrow, 9.2 ± 1.8 %ID; and the spleen, 4.6 ± 1.6 %ID. More than 90% of the blood activity was cleared with a half-life of 24 ± 3 min. The biologic half-life of the activity registered over the total body was long (69 ± 7 h). Excretion of the activity was almost exclusively through the urine (22.5 ± 3.5 %ID at 24 h), and hardly any activity was seen in the bowel or feces. Absorbed doses were found to be 196 ± 31 μGy/MBq for the kidneys, 41 ± 12 μGy/MBq for the spleen, 16.9 ± 1.3 μGy/MBq for the liver, and 8.4 ± 0.9 μGy/MBq for the red marrow. The effective dose was 11.0 ± 0.8 μSv/MBq, or 2.8 ± 0.2 mSv for the average injected activity of 250 MBq. No adverse effects were observed. Conclusion: 99m Tc-HYNIC-annexin V is a safe radiopharmaceutical, having a favorable biodistribution for imaging of apoptosis in the abdominal as well as thoracic area with an acceptable radiation dose.