Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [ 169 Yb]Yb 2 O 3 nanoseeds.

Autor: Ghosh S; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India., Patra S; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India., Younis MH; Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, USA., Chakraborty A; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India.; Radiation Medicine Centre, Bhabha Atomic Research Centre, Parel, Mumbai, 400012, India., Guleria A; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India.; Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India., Gupta SK; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India.; Radiochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India., Singh K; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India., Rakhshit S; Radiation Medicine Centre, Bhabha Atomic Research Centre, Parel, Mumbai, 400012, India., Chakraborty S; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India., Cai W; Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, USA. wcai@uwhealth.org., Chakravarty R; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India. rubelc@barc.gov.in.; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India. rubelc@barc.gov.in.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2024 May; Vol. 51 (6), pp. 1558-1573. Date of Electronic Publication: 2024 Jan 25.
DOI: 10.1007/s00259-024-06612-1
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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