Synthesis, Bio-Evaluation, and HumanAbsorbed Dose Estimation of 68Ga-Zoledronic Derivative for PET

Document Type : Research Article


1 Radiation Application Department, Shahid Beheshti University, Tehran, I.R. IRAN

2 Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, I.R. IRAN

3 Faculty of Engineering, Science and Research Branch, Islamic Azad University, Tehran, I.R. IRAN


Today, the development of PET-based diagnostic radiopharmaceuticals is essential due to their accessibility by generators such as gallium-68 radioisotope. In this study, due to the distinctive properties of the bone-seeking agent of DOTA-ZOL, an effort is created to synthesize this valuable compound and use it in labeling with gallium-68. Further preclinical studies of  68Ga-DOTA-ZOL are performed, and therefore the human absorbed dose after injection of the labeled compound was estimated based on rat biodistribution data. DOTA-ZOL was synthesized and characterized by FT-IR, NMR, and MS analyses. A tin-based in-house 68Ge /68Ga generator was used for labeling studies. To get the simplest labeling condition of DOTA-ZOL, completely different experiments were performed by variable labeling parameters together with concentration, time, pH, and time. The radiochemical purity of the radiolabeled complex was examined using RTLC methodology by totally different solvent systems. The steadiness of the final complex was assessed in PBS and human serum. The biodistribution of the radiolabeled complex as well as 68GaCl3 was evaluated in normal rats up to 120 min post-injection. The human-absorbed dose of the complex was estimated using animal data 68Ga-DOTA-ZOL and was prepared with radiochemical purity of quite 97 at optimized conditions using synthesized DOTA-ZOL and an in-house generator. The complex was stable in both PBS (4 °C) and in human blood serum (37 °C). The biodistribution studies in normal rats showed a high accumulation of 68Ga-DOTA-ZOL injection with the most uptake at 30 min. The human absorbed dose estimation of the radiolabeled compound showed the highest absorbed dose is received by the bone tissue with the equivalent dose of 0.052 mGy/MBq. The results showed the attainable preparation of a new emerging bone-seeking agent of 68Ga- DOTA-ZOL using an in-house generator. Also, the radiolabeled compound is considered an approximately safe radiopharmaceutical in terms of radiation absorbed dose.


Main Subjects

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