Introduction of Re-188 to enhance the inhibiting effect of Bevacizumab for Non-small-cell Lung Cancer

Objectives To strenghten the inhibiting effect of Bevacizumab (Bev) for non-small-cell lung cancer (NSCLC) by additive introduction of emitting beta rays of radionuclide, Re-188 was labeled to Bev, which was already proved effective in retarding the neovascularization of tumor.

Methods Re-188 was labeled to Bev using glucohepatonate as the transchelator. Two TLC systems were used to measure the product and 188Re-perrhenate, so as to detect the labeling rate and labeling stability of 188Re-Bev. Both in situ and xenograft NSCLC tumor models (n = 5 for each group) were prepared and then used for the evaluation of tumor response by the glycometabolism assessed by 18F-FDG PET, tumor size, and body weight. Injection dose of Bev referred to clinical applications, i.e., 5mg per kilogram body weight every week; for the beta-ray enhanced group, 18.5 MBq Re-188-labeled equal amount of Bev was injected intravenously. At the end of treatments, biopsies were performed for pathological evaluation of tumorous lesions so as to assess and compare the therapeutic efficiency.

Results Re-188 was labeled to Bev with > 97 % radiochemical purity, and no obvious de-labeling was measured in vitro for more than 24 hours. For in situ NSCLC tumor models, a more satisfactory outcome of 188Re-Bev was observed and reflected by the quicker decrease of focal SUVmean and SUVmax. Meanwhile, body weights were not significantly influenced by the introduction of Re-188. However, there was no obvious reduction of tumor volumes for xenograft NSCLC tumor model, probably resulting from the low uptake of Bev in the lesions of xenograft models.

Conclusions Introduction of Re-188 to Bevacizumab enhanced the therapeutic effect for NSCLC, and no harm to bodies was observed.