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

AbstractPurpose: 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 (Ktrans) 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 Ktrans, was seen at 3 h. No significant anti-tumour effects were observed in the C3H tumours until doses of 12.5 mg/kg wer...