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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

25.01.2024 | Original Article

Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [¹⁶⁹Yb]Yb₂O₃ nanoseeds

verfasst von: Sanchita Ghosh, Sourav Patra, Muhsin H. Younis, Avik Chakraborty, Apurav Guleria, Santosh K. Gupta, Khajan Singh, Sutapa Rakhshit, Sudipta Chakraborty, Weibo Cai, Rubel Chakravarty

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 6/2024

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Abstract

Purpose

Classical brachytherapy of solid malignant tumors is an invasive procedure which often results in an uneven dose distribution, while requiring surgical removal of sealed radioactive seed sources after a certain period of time. To circumvent these issues, we report the synthesis of intrinsically radiolabeled and gum Arabic glycoprotein functionalized [¹⁶⁹Yb]Yb₂O₃ nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy.

Methods

¹⁶⁹Yb (T_½ = 32 days) was produced by neutron irradiation of enriched (15.2% in ¹⁶⁸Yb) Yb₂O₃ target in a nuclear reactor, radiochemically converted to [¹⁶⁹Yb]YbCl₃ and used for nanoparticle (NP) synthesis. Intrinsically radiolabeled NP were synthesized by controlled hydrolysis of Yb³⁺ ions in gum Arabic glycoprotein medium. In vivo SPECT/CT imaging, autoradiography, and biodistribution studies were performed after intratumoral injection of radiolabeled NP in B16F10 tumor bearing C57BL/6 mice. Systematic tumor regression studies and histopathological analyses were performed to demonstrate therapeutic efficacy in the same mice model.

Results

The nanoformulation was a clear solution having high colloidal and radiochemical stability. Uniform distribution and retention of the radiolabeled nanoformulation in the tumor mass were observed via SPECT/CT imaging and autoradiography studies. In a tumor regression study, tumor growth was significantly arrested with different doses of radiolabeled NP compared to the control and the best treatment effect was observed with ~ 27.8 MBq dose. In histopathological analysis, loss of mitotic cells was apparent in tumor tissue of treated groups, whereas no significant damage in kidney, lungs, and liver tissue morphology was observed.

Conclusions

These results hold promise for nanoscale brachytherapy to become a clinically practical treatment modality for unresectable solid cancers.

Graphical Abstract

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Titel: Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [169Yb]Yb2O3 nanoseeds
verfasst von: Sanchita Ghosh
Sourav Patra
Muhsin H. Younis
Avik Chakraborty
Apurav Guleria
Santosh K. Gupta
Khajan Singh
Sutapa Rakhshit
Sudipta Chakraborty
Weibo Cai
Rubel Chakravarty
Publikationsdatum: 25.01.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 6/2024
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-024-06612-1

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [¹⁶⁹Yb]Yb₂O₃ nanoseeds

Abstract

Purpose

Methods

Results

Conclusions

Graphical Abstract

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Graphical Abstract

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