Preliminary imaging studies of [61Cu]diacetyl-bis (N4-methylthiosemi-carbazone) in normal and hypoxic tumor models

Jalilian, Amir Reza; Yousefnia, Hassan; Kamali-Dehghan, Mohsen; Moradkhani, Sedigheh; Bolourinovin, Fatemeh; Shafaii, Kamaleddin; Aslani, Gholamreza

Preliminary imaging studies of [61Cu]diacetyl-bis (N4-methylthiosemi-carbazone) in normal and hypoxic tumor models

Document Type : Original Article

Authors

Amir Reza Jalilian ¹

Hassan Yousefnia ¹

Mohsen Kamali-Dehghan ²

Sedigheh Moradkhani ²

Fatemeh Bolourinovin ²

Kamaleddin Shafaii ²

Gholamreza Aslani ²

¹ Radiopharmaceutical Research and Development Laboratory, Nuclear Science and Technology Research Institute, Atomic Energy organization of Iran, Tehran, Iran

² Agricultural, Medical and Industrial research School, Nuclear Science and Technology Research Institute, Atomic Energy organization of Iran, Karaj, Iran

Abstract

Introduction: [⁶¹Cu]diacetyl-bis(N⁴-methylthiosemicarbazone) ([⁶¹Cu]ATSM) is a well-established hypoxia imaging tracer with simple production and significant specifity. In this work the accumulation of the tracer is studied in wild-type, necrotic and hypoxic fibrosarcoma tumors.
Methods: [⁶¹Cu]ATSM was prepared using ATSM ligand and [⁶¹Cu]CuOAc followed by i.v. administration and imaging studies in wild-type rats and hypoxic fibrosarcoma-bearing mice.
Results: [⁶¹Cu]ATSM with high radiochemical purity (>99%, HPLC, RTLC) was injected to wild-type rats as well as hypoxic and necrotic fibrosarcoma-bearing mice followed by imaging up to 3 hours.
Conclusion: [⁶¹Cu]ATSM was mainly accumulated in liver, as well as kidney and bladder and less but still significant in brain of wild-type rats. A significant and hypoxia-specific tumor/non tumor ratio in hypoxic models was observed by co-incidence imaging 2 h post injection, while in necrotic and 12-week tumor-induced mice very slight tumor uptakes were detected. [⁶¹Cu]ATSM is a positron emission tomography (PET) radiotracer for selective tumor hypoxia imaging from necrotic and proliferative tumors.

Keywords

[61Cu]ATSM

Copper radiopharmaceuticals

Hypoxia

Co-incidence imaging

Fibrosarcoma

Subjects