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

Abstract

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.