Enhancing 223Ra Treatment Efficacy by Anti- β1 Integrin Targeting.

Claudia Paindelli, Stefano Casarin, Feng Wang, Luis Diaz-Gomez, Jianhua Zhang, Antonios G. Mikos, Christopher J. Logothetis, Peter Friedl, Eleonora Dondossola

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


223Ra is an α-emitter approved for the treatment of bone metastatic prostate cancer (PCa), which exerts direct cytotoxicity toward PCa cells near the bone interface, whereas cells positioned in the core respond poorly because of short α-particle penetrance. β1 integrin (β1I) interference has been shown to increase radiosensitivity and significantly enhance external-beam radiation efficiency. We hypothesized that targeting β1I would improve 223Ra outcome. Methods: We tested the effect of combining 223Ra and anti-β1I antibody treatment in PC3 and C4-2B PCa cell models expressing high and low β1I levels, respectively. In vivo tumor growth was evaluated through bioluminescence. Cellular and molecular determinants of response were analyzed by ex vivo 3-dimensional imaging of bone lesions and by proteomic analysis and were further confirmed by computational modeling and in vitro functional analysis in tissue-engineered bone mimetic systems. Results: Interference with β1I combined with 223Ra reduced PC3 cell growth in bone and significantly improved overall mouse survival, whereas no change was achieved in C4-2B tumors. Anti-β1I treatment decreased the PC3 tumor cell mitosis index and spatially expanded 223Ra lethal effects 2-fold, in vivo and in silico. Regression was paralleled by decreased expression of radioresistance mediators. Conclusion: Targeting β1I significantly improves 223Ra outcome and points toward combinatorial application in PCa tumors with high β1I expression.

Original languageEnglish (US)
Pages (from-to)1039-1045
Number of pages7
JournalJournal of Nuclear Medicine
Issue number7
StatePublished - Jul 1 2022


  • Radium 223
  • bone metastasis
  • integrin beta 1 Running Title: Enhancing Radium 223 efficacy
  • prostate cancer
  • Integrins/antagonists & inhibitors
  • Integrin beta1/metabolism
  • Humans
  • Male
  • Treatment Outcome
  • Animals
  • Bone Neoplasms/diagnostic imaging
  • Prostatic Neoplasms/pathology
  • Proteomics
  • Cell Line, Tumor
  • Mice

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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