A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

Micah John Luderer, Barbara Muz, Pilar de la Puente, Sanmathi Chavalmane, Vaishali Kapoor, Raymundo Marcelo, Pratim Biswas, Dinesh Thotala, Buck Rogers, Abdel Kareem Azab

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Purpose: Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. Methods: B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. Results: B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. Conclusions: B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

Original languageEnglish
Pages (from-to)2530-2539
Number of pages10
JournalPharmaceutical Research
Issue number10
StatePublished - Oct 1 2016


  • BNCT
  • boron neutron capture therapy
  • glioma
  • hypoxia
  • tumor targeting


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