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

• Published in: European journal of nuclear medicine and molecular imaging Vol. 51; no. 6; pp. 1558 - 1573
• Main Authors: Ghosh, Sanchita, Patra, Sourav, Younis, Muhsin H., Chakraborty, Avik, Guleria, Apurav, Gupta, Santosh K., Singh, Khajan, Rakhshit, Sutapa, Chakraborty, Sudipta, Cai, Weibo, Chakravarty, Rubel
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2024; Springer Nature B.V
• Subjects: Autoradiography; Brachytherapy; Cancer therapies; Cardiology; Computed tomography; Glycoproteins; Imaging; In vivo methods and tests; Medical imaging; Medicine; Medicine & Public Health; Nanoparticles; Neutron irradiation; Neutron radiation; Nuclear Medicine; Nuclear reactors; Oncology; Original Article; Orthopedics; Radiation therapy; Radiochemical analysis; Radiology; Single photon emission computed tomography; Tumors; Radiolabeled nanoparticles; Nanoscale brachytherapy; Theranostics; Intratumoral injection; SPECT; Tumor regression; Cancer
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-024-06612-1

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 [ 169 Yb]Yb 2 O 3 nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy. Methods 169 Yb ( T ½  = 32 days) was produced by neutron irradiation of enriched (15.2% in 168 Yb) Yb 2 O 3 target in a nuclear reactor, radiochemically converted to [ 169 Yb]YbCl 3 and used for nanoparticle (NP) synthesis. Intrinsically radiolabeled NP were synthesized by controlled hydrolysis of Yb 3+ 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