Tehran University of Medical Sciences Frontiers in Biomedical Technologies 2345-5837 0 0 2026 07 18 1433 1433 Samaneh Zolghadri Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran Sara Vosoughi Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran Nafiseh Salek Nuclear Fuel Research School, Nuclear Science and Technology Research Institute, Tehran, Iran Mohsen Mehrabi Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran Hassan Yousefnia Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran 2025 08 11 2026 01 02 Objective: The aim of this preclinical study was to evaluate the dosimetry and radiation safety of [64Cu]Cu-DOTATATE, a promising PET radiopharmaceutical for imaging SSTR2-positive neuroendocrine tumors (NETs), and to establish its potential for clinical translation. Materials and Methods: [64Cu]Cu-DOTATATE was synthesized by radiolabeling DOTATATE with [64Cu]CuCl₂, and its radiochemical purity was assessed using HPLC and RTLC. Biodistribution studies were conducted in rats at 2, 4, 12, and 24 h post-injection, and the organs' radioactivity was measured using an HPGe detector. Dosimetry calculations were performed based on the MIRD schema using animal biodistribution data to estimate absorbed doses in human organs. Results: [64Cu]Cu-DOTATATE demonstrated excellent radiochemical purity (>99%) and stability over 12 h in PBS and human serum. Biodistribution analysis showed rapid blood clearance and high uptake in SSTR2-expressing organs, such as the pancreas and adrenals, with renal excretion as the primary elimination route. The estimated absorbed doses in key organs were highest in the pancreas (0.205 mGy/MBq), followed by kidneys and liver. Comparative dosimetry with other SSTR-targeted agents, like 68Ga-DOTATATE, revealed similar or lower radiation doses in non-target organs. Conclusion: [64Cu]Cu-DOTATATE exhibited favorable pharmacokinetics and an acceptable radiation dose profile, supporting its potential as a safe and effective PET imaging agent for SSTR2-positive NETs. The extended half-life of [64Cu] enhances its clinical utility with improved tumor-to-background contrast and centralized production logistics, paving the way for its use in clinical settings. https://fbt.tums.ac.ir/index.php/fbt/article/view/1433 https://fbt.tums.ac.ir/index.php/fbt/article/download/1433/577