Preliminary efficacy of [(90)Y]DOTA-biotin-avidin radiotherapy against non-muscle invasive bladder cancer Journal Article
| Authors: | Alì, A.; Leibowitz, D.; Bhatt, N.; Doubrovin, M.; Spina, C. S.; Bates-Pappas, G. E.; Taub, R. N.; McKiernan, J. M.; Mintz, A.; Molotkov, A. |
| Article Title: | Preliminary efficacy of [(90)Y]DOTA-biotin-avidin radiotherapy against non-muscle invasive bladder cancer |
| 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. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. |
| Keywords: | bladder cancer; avidin; intravesical radionuclide therapy; [90y]dota-biotin-avidin |
| Journal Title: | European Journal of Nuclear Medicine and Molecular Imaging |
| Volume: | 50 |
| Issue: | 3 |
| ISSN: | 1619-7070 |
| Publisher: | Springer |
| Date Published: | 2023-02-01 |
| Start Page: | 692 |
| End Page: | 700 |
| Language: | English |
| DOI: | 10.1007/s00259-022-06027-w |
| PUBMED: | 36350400 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2023 -- Source: Scopus |
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