English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Small cell lung cancer (SCLC) is an aggressive tumor and prognosis remains poor. Therefore, the development of more effective therapy is needed. We previously reported that high levels of an anti-c-kit antibody (12A8) accumulated in SCLC xenografts. In the present study, we evaluated the efficacy of two antibodies (12A8 and 67A2) for radioimmunotherapy (RIT) of an SCLC mouse model by labeling with the  90 Y isotope.   Methods    111 In- or  125 I-labeled antibodies were evaluated  in vitro  by cell binding, competitive inhibition and cellular internalization assays in c-kit-expressing SY cells and  in vivo  by biodistribution in SY-bearing mice. Therapeutic efficacy of  90 Y-labeled antibodies was evaluated in SY-bearing mice upto day 28 and histological analysis was conducted at day 7.    Results  [ 111 In]12A8 and [ 111 In]67A2 specifically bound to SY cells with high affinity (8.0 and 1.9 nM, respectively). 67A2 was internalized similar to 12A8. High levels of [ 111 In]12A8 and [ 111 In]67A2 accumulated in tumors, but not in major organs. [ 111 In]67A2 uptake by the tumor was 1.7 times higher than for [ 111 In]12A8. [ 90 Y]12A8, but not [ 90 Y]67A2, suppressed tumor growth in a dose-dependent manner. Tumors treated with 3.7 MBq of [ 90 Y]12A8, and 1.85 and 3.7 MBq of [ 90 Y]67A2 (absorbed doses were 21.0, 18.0 and 35.9 Gy, respectively) almost completely disappeared approximately 2 weeks after injection, and regrowth was not observed except for in one mouse treated with 1.85 MBq [ 90 Y]67A2. The area of necrosis and fibrosis increased depending on the RIT effect. Apoptotic cell numbers increased with increased doses of [ 90 Y]12A8, whereas no dose-dependent increase was observed following [ 90 Y]67A2 treatment. Body weight was temporarily reduced but all mice tolerated the RIT experiments well.    Conclusion  Treatment with [ 90 Y]12A8 and [ 90 Y]67A2 achieved a complete therapeutic response when SY tumors received an absorbed dose greater than 18 Gy and thus are promising RIT agents for metastatic SCLC cells at distant sites.

Therapeutic Efficacy of C-Kit-Targeted Radioimmunotherapy Using 90Y-Labeled Anti-C-Kit Antibodies in a Mouse Model of Small Cell Lung Cancer