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

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Abstract 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-hours, but returning to normal within 24-hours. A dose-dependent decrease in IAUC and K(trans), was seen at 3-hours. 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-hour 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.
Original languageEnglish
JournalInternational Journal of Radiation Biology
Pages (from-to)1126-1134
Number of pages9
Publication statusPublished - Nov 2011

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