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

• DOI: 10.3109/09553002.2011.605418
• Publication Date: 2011-08-04T19:05:06Z
• Authors: Lotte B. Bertelsen; Yuan Yuan Shen; Thomas Nielsen; Hans Stødkilde-Jø...; G. Kenneth Lloyd; Dietmar W. Siemann; Michael R. Horsman
• Keywords: Clonogenic assay

Purpose: This study investigated the anti-tumour effects of novel vascular disrupting agent plinabulin (NPI-2358) when given alone or combined with radiation.Materials and methods: Foot implanted C3H mammary carcinomas leg KHT sarcomas were used, injected intraperitoneally. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measurements made gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) on a 7-tesla magnet. Treatment response was assessed using regrowth delay (C3H tumours), clonogenic survival (KHT sarcomas) histological estimates necrosis for both models.Results: Plinabulin (7.5 mg/kg) significantly reduced initial area under curve (IAUC) transfer constant (Ktrans) within 1 hour after injection, reaching nadir at 3 h, but returning to normal 24 h. A dose-dependent decrease in IAUC Ktrans, seen No significant observed tumours until doses 12.5 mg/kg achieved, started 1.5 sarcoma. Irradiating h injecting enhanced models.Conclusions: induced time- tumour perfusion. The sarcoma more sensitive than plinabulin, while radiation models.