Vascular effects of plinabulin (NPI-2358) and the influence on tumour response when given alone or combined with radiation

Int J Radiat Biol. 2011 Nov;87(11):1126-34. doi: 10.3109/09553002.2011.605418.


Purpose: This study investigated the anti-tumour effects of the novel vascular disrupting agent plinabulin (NPI-2358) when given alone or combined with radiation.

Materials and methods: Foot implanted C3H mammary carcinomas or leg implanted KHT sarcomas were used, with plinabulin injected intraperitoneally. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measurements were made with gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) on a 7-tesla magnet. Treatment response was assessed using regrowth delay (C3H tumours), clonogenic survival (KHT sarcomas) or histological estimates of necrosis for both models.

Results: Plinabulin (7.5 mg/kg) significantly reduced the initial area under curve (IAUC) and the transfer constant (K(trans)) within 1 hour after injection, reaching a nadir at 3 h, but returning to normal within 24 h. A dose-dependent decrease in IAUC and K(trans), was seen at 3 h. No significant anti-tumour effects were observed in the C3H tumours until doses of 12.5 mg/kg were achieved, but started at 1.5 mg/kg in the KHT sarcoma. Irradiating tumours 1 h after injecting plinabulin enhanced response in both models.

Conclusions: Plinabulin induced a time- and dose-dependent decrease in tumour perfusion. The KHT sarcoma was more sensitive than the C3H tumour to the anti-tumour effects of plinabulin, while radiation response was enhanced in both models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Chemoradiotherapy
  • Diketopiperazines
  • Dose-Response Relationship, Drug
  • Female
  • Imidazoles / therapeutic use*
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / radiotherapy
  • Mice
  • Mice, Inbred C3H
  • Piperazines / therapeutic use*
  • Sarcoma, Experimental / drug therapy
  • Sarcoma, Experimental / pathology
  • Sarcoma, Experimental / radiotherapy


  • Antineoplastic Agents
  • Diketopiperazines
  • Imidazoles
  • NPI 2358
  • Piperazines