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      1. Author :
        Rusckowski, Mary; Wang, Yuzhen; Blankenberg, Francis G; Levashova, Zoia; Backer, Marina V; Backer, Joseph M
      2. Title :
        Targeted scVEGF/177Lu radiopharmaceutical inhibits growth of metastases and can be effectively combined with chemotherapy
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        EJNMMI Research
      6. Products :
      7. Volume :
        6
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VEGF receptors,; 177Lu,; Targeted radiopharmaceutical,; Breast cancer,; Metastases; IVIS; IVIS BLI in vivo
      12. Abstract :
        Background: scVEGF/177Lu is a novel radiopharmaceutical targeted by recombinant single-chain (sc) derivative of vascular endothelial growth factor (VEGF) that binds to and is internalized by vascular endothelial growth factor receptors (VEGFR). scVEGF/177Lu potential as adjuvant and neoadjuvant anti-angiogenic therapy was assessed in metastatic and orthotopic mouse models of triple-negative breast cancer. Methods: Metastatic lesions in Balb/c mice were established by intracardiac injection of luciferase-expressing 4T1luc mouse breast carcinoma cells. Mice with metastatic lesions received single intravenous (i.v.) injection of well-tolerated dose of scVEGF/177Lu (7.4 MBq/mouse) at day 8 after 4T1luc cell injection. Primary orthotopic breast tumors in immunodeficient mice were established by injecting luciferase-expressing MDA231luc human breast carcinoma cells into mammary fat pad. Tumor-bearing mice were treated with single injections of scVEGF/177Lu (7.4 MBq/mouse, i.v), or liposomal doxorubicin (Doxil, 1 mg doxorubicin per kg, i.v.), or with a combination of Doxil and scVEGF/177Lu given at the same doses, but two hours apart. “Cold” scVEGF-targeting conjugate was included in controls and in Doxil alone group. The effects of treatments were defined by bioluminescent imaging (BLI), computed tomography (CT), computed microtomography (microCT), measurements of primary tumor growth, and immunohistochemical analysis. Results: In metastatic model, adjuvant treatment with scVEGF/177Lu decreased overall metastatic burden and improved survival. In orthotopic primary tumor model, a combination of Doxil and scVEGF/177Lu was more efficient in tumor growth inhibition than each treatment alone. scVEGF/177Lu treatment decreased immunostaining for VEGFR-1, VEGFR-2, and pro-tumorigenic M2-type macrophage marker CD206. Conclusions: Selective targeting of VEGFR with well-tolerated doses of scVEGF/177Lu is effective in metastatic and primary breast cancer models and can be combined with chemotherapy. As high level of VEGFR expression is a common feature in a variety of cancers, targeted delivery of 177Lu for specific receptor-mediated uptake warrants further exploration.
      13. URL :
        N/A
      14. Call Number :
        PKI @ user @ 10761
      15. Serial :
        19542