Purpose: Bladder cancer represents 3% of all new cancer diagnoses per year. We propose intravesical radionuclide therapy using the β-emitter 90 Y linked to DOTA-biotin-avidin ([ 90 Y]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 68 Ga and dynamic microPET imaging following intravesical infusion of [ 68 Ga]DBA for up to 4 hours and post-necropsy γ-counting of organs. The antitumor activity of [ 90 Y]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 [ 90 Y]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 [ 90 Y]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 hours after intravesical infusion. A single dose of [ 90 Y]DBA radiation treatment significantly reduced growth of MB49 bladder carcinoma. Attaching 90 Y to the DOTA-avidin prevents its re-absorption into the blood and distribution throughout the rest of the body. Furthermore, immunohistochemistry demonstrated that [ 90 Y]DBA radiation treatment did not irreversibly damage the bladder urothelium, which appeared similar to the normal urothelium of healthy mice.
Conclusion: Our data demonstrates the potential of intravesical [ 90 Y]DBA as a treatment for non-muscle invasive bladder cancer.