Evaluation of the Safety and Pharmacokinetic Analysis of the Radiopharmaceutical [99mTc]Tc-DB8 in Breast Cancer Patients

Purpose: To evaluate the safety and pharmacokinetics of the radiopharmaceutical agent [99mTc]Tc-DB8 in patients with breast cancer. Material and methods: The study included 15 patients diagnosed with breast cancer (T2‒4 N0‒3 M0‒1) prior to any systemic or local treatment. Patients were divided into three groups based on the administered protein dose: 40 µg, 80 µg, and 120 µg (5 patients per group). Throughout the study, participants were under continuous clinical observation, which included assessment of symptoms, measurement of blood pressure (BP), body temperature, and heart rate prior to injection, and at 2, 4, 6, 24, and 48 hours post-injection. Additionally, complete blood count, biochemical blood analysis, and electrocardiography were performed before the injection, and again at 24 and 48 hours post-administration. To assess the elimination rate of [99mTc]Tc-DB8 from the bloodstream, its distribution in organs and tissues, and the associated radiation dose, whole-body planar scintigraphy was conducted at 2, 4, 6, and 24 hours after radiopharmaceutical administration at doses of 40, 80, and 120 µg. The average administered activity was 334 ± 84 MBq, with a radiochemical purity exceeding 95 %. Results: Injection of [99mTc]Tc-DB8 was not associated with any reported complaints or clinically significant changes in blood pressure, heart rate, or body temperature at any of the time points, regardless of dose. No significant deviations were observed in complete blood count, biochemical parameters, urinalysis, or ECG prior to injection, or at 48 hours and 7 days post-administration. The elimination half-life was 2.363 h for the 40 µg and 80 µg doses, and 2.233 h for the 120 µg dose. The highest absorbed doses were recorded in the mammary glands, kidneys, adrenal glands, pancreas, thyroid gland, urinary bladder and ovaries. The effective dose was 0.009 ± 0.001 mSv/MBq for the 40 µg dose, 0.011 ± 0.004 mSv/MBq for the 80 µg dose, and 0.014 ± 0.003 mSv/MBq for the 120 µg dose. Conclusion: The drug is safe at all stages of dynamic follow-up, which is confirmed by the subjective feelings of breast cancer patients and the absence of pathological changes according to laboratory and instrumental studies, which allows the continuation of the next stages of clinical trials. Similarly, [99mTc]Tc-DB8 demonstrated rapid elimination from the bloodstream when using 40, 80 and 120 micrograms of protein, and the highest absorption was recorded in the mammary gland, kidneys, adrenal glands, pancreas, thyroid, bladder and ovaries. Based on the results of the completed analysis, the use of the drug [99mTc]Tc-DB8 served as the basis for further studies.