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

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).

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.

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.

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

European journal of nuclear medicine and molecular imaging. 2022 Nov 09 [Epub ahead of print]

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

Department of Radiology, Columbia University Irving Medical Center, New York, NY, 10032, USA., Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY, 10032, USA., Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, 10021, USA., Department of Medicine (Retired), Columbia University Irving Medical Center, New York, NY, 10032, USA., Department of Urology, Columbia University Irving Medical Center, New York, NY, 10032, USA., Department of Radiology, Columbia University Irving Medical Center, New York, NY, 10032, USA. .

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