Hafnium Complexes as Contrast Media and Dose Enhancing Agents for Radiology and Contrast-Enhanced Radiotherapy

Hafnium is a promising element as contrast agent for diagnostic and therapeutic radiology. Currently there are no suitable hafnium drugs with renal excretion which can be used in radiology. In this work two new hafnium complexes with nitrilotriacetic acid (Hf-NTA) and 1,2-diaminocyclohexanetetraacetic acid (Hf-CDTA) were synthesized and studied for acute toxicity and biodistribution. Inorganic chemistry methods were used for Hf-NTA and Hf-CDTA synthesis. Acute toxicity was studied in female mice C57Bl/6. Median lethal dose (LD50) of Hf-CDTA was assessed as 408 ± 64 mg Hf/kg and of Hf-NTA less than 120 mg Hf/kg. Biodistribution and contrast properties studies of Hf-CDTA were performed in vivo using micro-CT in mice with transplanted subcutaneous mammary adenocarcinoma Ca755. CT imaging of mice intravenously injected with Hf-CDTA confirmed its renal excretion and contrast capability. CT imaging of tumor region with single intratumoral administration of Hf-CDTA showed promising hafnium concentration and retention in tumor for use in contrast-enhanced radiotherapy. Hf-CDTA showed acceptable toxicity and biodistribution in mice with subcutaneous tumors for biomedical application in radiology and radiotherapy. For diagnostic clinical application, the Hf-CDTA formulation must be improved to increase water solubility and decrease toxicity. Hf-NTA appeared to be unacceptably toxic for radiological application.