Enhanced Theranostic Efficacy of 89 Zr and 177 Lu-Labeled Aflibercept in Renal Cancer: A Viable Option for Clinical Practice

• Published in: Molecular pharmaceutics 2024-05, Vol.21 (5), p.2544-2554
• Main Authors: Chen, Zhao, Yang, Qi, Song, Lele, Qiu, Yongkang, Wang, Tianyao, Wu, Sitong, Huang, Wenpeng, Sun, Xinyao, Wang, Aixiang, Kang, Lei
• Format: Article
• Language: English
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.4c00084

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of Lu/ Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [ Zr]Zr-Abe, [ Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [ Zr]Zr-Abe and [ Lu]Lu-Abe was performed. Additionally, the [ Lu]Lu-Abe, [ Lu]Lu-Abe-block, Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [ Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with Lu and Df-Abe with Zr in our study. The uptake in tumor of [ Zr]Zr-Abe was significantly higher than that of [ Zr]Zr-Abe-block ( < 0.05) and provided excellent tumor contrast in PET images. [ Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [ Lu]Lu-Abe was significantly smaller than those of other treatment groups ( < 0.05). [ Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group ( < 0.05). In conclusion, [ Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [ Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.