Development of a multifunctional platform for near-infrared imaging and targeted radionuclide therapy for tumors

Biotin receptor (BR) is overexpressed in several human tumor cell lines and has become an important biomarker for tumor diagnosis and treatment. Therefore, much attention has been attracted in the field of developing BR-targeting agents. In clinical practice, a multifunctional platform that can be used for both diagnosis and treatment is much desirable. In this study, to improve diagnostic and therapeutic efficacy of BR-positive tumors, we developed a multifunctional platform RT-H₂ to combine with the cyanine scaffold for near infrared (NIR) imaging and the radioisotope ¹³¹I for targeted radionuclide therapy (TRT). In vitro experiments showed that RT-H₂ possessed favorable NIR properties and could selectively accumulate in BR-positive HeLa cells. In vivo NIR imaging of HeLa tumor-bearing mice exhibited high accumulation and long retention time (72 h) of RT-H₂ in the tumor. Furthermore, RT-H₂ was also employed as a carrier to develop ¹³¹I-labeled TRT agent due to its favorable properties in vivo. The radiolabeling conditions were optimized and the optimal conditions determined to be 1.2 equiv of Idogen, reaction time 4 min and room temperature, yielding the radiotracer [¹³¹I]I-RT-H₂ with the radiochemical purity (RCP) of > 95% after a simple purification by a C18 column. In vitro cell experiments indicated that [¹³¹I]I-RT-H₂ could specifically target Hela cells and displayed dose-dependent antitumor effect. In vivo experiments demonstrated that [¹³¹I]I-RT-H₂ obviously inhibited the tumor proliferation in HeLa tumor-bearing mice within 4 weeks. All these results indicate that RT-H₂ has the potential to serve as a multifunctional platform for tumor diagnosis and treatment.