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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

09-11-2022 | Radionuclide Therapy | Original Article

Preliminary efficacy of [⁹⁰Y]DOTA-biotin-avidin radiotherapy against non-muscle invasive bladder cancer

Authors: Alessandra Alì, Dev Leibowitz, Nikunj Bhatt, Mikhail Doubrovin, Catherine S. Spina, Gleneara E. Bates-Pappas, Robert N. Taub, James M. McKiernan, Akiva Mintz, Andrei Molotkov

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2023

Abstract

Purpose

Bladder cancer represents 3% of all new cancer diagnoses per year. We propose intravesical radionuclide therapy using the β-emitter ⁹⁰Y linked to DOTA-biotin-avidin ([⁹⁰Y]DBA) to deliver short-range radiation against non-muscle invasive bladder cancer (NMIBC).

Material and methods

Image-guided biodistribution of intravesical DBA was investigated in an animal model by radiolabeling DBA with the ⁶⁸Ga and dynamic microPET imaging following intravesical infusion of [⁶⁸Ga]DBA for up to 4 h and post-necropsy γ-counting of organs. The antitumor activity of [⁹⁰Y]DBA was investigated using an orthotopic MB49 murine bladder cancer model. Mice were injected with luciferase-expressing MB49 cells and treated via intravesical administration with 9.2 MBq of [⁹⁰Y]DBA or unlabeled DBA 3 days after the tumor implantation. Bioluminescence imaging was conducted after tumor implantation to monitor the bladder tumor growth. In addition, we investigated the effects of [⁹⁰Y]DBA radiation on urothelial histology with immunohistochemistry analysis of bladder morphology.

Results

Our results demonstrated that DBA is contained in the bladder for up to 4 h after intravesical infusion. A single dose of [⁹⁰Y]DBA radiation treatment significantly reduced growth of MB49 bladder carcinoma. Attaching ⁹⁰Y-DOTA-biotin to avidin prevents its re-absorption into the blood and distribution throughout the rest of the body. Furthermore, immunohistochemistry demonstrated that [⁹⁰Y]DBA radiation treatment did not cause short-term damage to urothelium at day 10, which appeared similar to the normal urothelium of healthy mice.

Conclusion

Our data demonstrates the potential of intravesical [⁹⁰Y]DBA as a treatment for non-muscle invasive bladder cancer.

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Title: Preliminary efficacy of [90Y]DOTA-biotin-avidin radiotherapy against non-muscle invasive bladder cancer
Authors: Alessandra Alì
Dev Leibowitz
Nikunj Bhatt
Mikhail Doubrovin
Catherine S. Spina
Gleneara E. Bates-Pappas
Robert N. Taub
James M. McKiernan
Akiva Mintz
Andrei Molotkov
Publication date: 09-11-2022
Publisher: Springer Berlin Heidelberg
Keyword: Radionuclide Therapy
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2023
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-06027-w

2024 ASCO Annual Meeting

Springer Medicine

Preliminary efficacy of [⁹⁰Y]DOTA-biotin-avidin radiotherapy against non-muscle invasive bladder cancer

Abstract

Purpose

Material and methods

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Purpose

Material and methods

Results

Conclusion

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