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

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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 (T½ = 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.

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Acknowledgements

The authors are grateful for the financial support from the Bhabha Atomic Research Centre (BARC), the National Institutes of Health (P30 CA014520 and T32 CA009206), and the University of Wisconsin-Madison. The authors from BARC are grateful to Dr. P. K. Mohapatra, Associate Director, Radiochemistry and Isotope Group, BARC, Dr. Sandip Basu, Head, Radiation Medicine Centre (Medical), BARC and Dr. Tapas Das, Head, Radiopharmaceuticals Division, BARC for their support to this work. Dr. A.K. Debnath, Technical Physics Division, BARC, is acknowledged for providing the XPS data. The Sophisticated Analytical Instrumentation Facility of the Indian Institute of Technology Bombay is gratefully acknowledged for the HRTEM analysis of the samples.

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Authors and Affiliations

  1. Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India

    Sanchita Ghosh, Sourav Patra, Khajan Singh, Sudipta Chakraborty & Rubel Chakravarty

  2. Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India

    Sanchita Ghosh, Sourav Patra, Avik Chakraborty, Apurav Guleria, Santosh K. Gupta, Sudipta Chakraborty & Rubel Chakravarty

  3. Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, USA

    Muhsin H. Younis & Weibo Cai

  4. Radiation Medicine Centre, Bhabha Atomic Research Centre, Parel, Mumbai, 400012, India

    Avik Chakraborty & Sutapa Rakhshit

  5. Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India

    Apurav Guleria

  6. Radiochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India

    Santosh K. Gupta

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  1. Sanchita Ghosh
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Correspondence to Weibo Cai or Rubel Chakravarty.

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All animal studies were performed according to the guidelines of the Animal Care and Use Committee of the Bhabha Atomic Research Centre, India.

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Weibo Cai declares conflict of interest with the following corporations: Actithera, Inc., Rad Source Technologies, Inc., Portrai, Inc., rTR Technovation Corporation, and Four Health Global Pharmaceuticals Inc. All other authors declare that they have no conflict of interest.

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Ghosh, S., Patra, S., Younis, M.H. et al. Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [169Yb]Yb2O3 nanoseeds. Eur J Nucl Med Mol Imaging 51, 1558–1573 (2024). https://doi.org/10.1007/s00259-024-06612-1

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