Hafnium Complexes as Dose Enhancement Agents for Photon Capture Therapy and as Contrast Agents for Radiotherapy

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Abstract

Hafnium is a promising element as contrast agent for diagnostic and therapeutic radiology. Currently there is 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. Biodistribution and contrast properties studies of Hf-CDTA were made in vivo with micro-CT. Mice with transplanted subcutaneous mammary adenocarcinoma Ca755 were used for the study. 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. 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 Hf-CDTA formulation must be improved to increase water solubility and decrease toxicity. Hf-NTA appeared to be unacceptably toxic for radiological application.

About the authors

A. A Lipengolts

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation; National Research Nuclear University (Moscow Engineering Physics Institute); N.S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences

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Kashirskoye Shosse 24, Moscow, 115478, Russia; Kashirskoe shosse 31, Moscow, 115409, Russia; Leninsky prosp. 31, Moscow, 119991, Russia

V. A Skribitsky

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation; National Research Nuclear University (Moscow Engineering Physics Institute)

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Kashirskoye Shosse 24, Moscow, 115478, Russia; Kashirskoe shosse 31, Moscow, 115409, Russia

Yu. A Finogenova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation; Peoples' Friendship University of Russia named after Patrice Lumumba

Email: b-f.finogenova@yandex.ru
Kashirskoye Shosse 24, Moscow, 115478, Russia; ul. Miklukho-Maklaya 6, Moscow, 117198, Russia

A. T Shulyak

N.S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences; Peoples' Friendship University of Russia named after Patrice Lumumba; MIREA – Russian Technological University; Leninsky prosp. 31, Moscow, 119991, Russia

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ul. Miklukho-Maklaya 6, Moscow, 117198, Russia; prosp. Vernadskogo 78, Moscow, 119454, Russia

M. A Abakumov

N.I. Pirogov Russian National Research Medical University

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ul. Ostrovityanova 1, Moscow, 117997, Russia

A. Yu Bykov

N.S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences

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Leninsky prosp. 31, Moscow, 119991, Russia

E. Yu Grigorieva

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation

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Kashirskoye Shosse 24, Moscow, 115478, Russia

A. V Smirnova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation; Moscow Clinical Research Center named after A. S. Loginov, Moscow Healthcare Department

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Kashirskoye Shosse 24, Moscow, 115478, Russia; Shosse Entuziastov 86, Moscow, 111123, Russia

K. E Shpakova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation; National Research Nuclear University (Moscow Engineering Physics Institute)

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Kashirskoye Shosse 24, Moscow, 115478, Russia; Kashirskoe shosse 31, Moscow, 115409, Russia

K. Yu Zhizhin

N.S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences; MIREA – Russian Technological University

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Leninsky prosp. 31, Moscow, 119991, Russia; prosp. Vernadskogo 78, Moscow, 119454, Russia

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