Study of the new minimally-invasive proton therapy with antivascular effects

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Antitumor effects of the proton therapy in combination with the combretastatin A-4 derivative, AVE8062 were studied by using NFSa fibrosarooma implanted into the hind legs of C3H/He mice in order to investigate the minimally invasive treatment technique in proton therapy with antivassular effects.The proton therapy facilities for small animals were developed to perform the treatment experiments on the tumor mouse model at Cyclotron and Radioisotope Center (CYRIC), Tohoku University. In addition, proton-irradiation experiments with a dog tumor cell of squamous cell carcinoma were performed to derive the relative biological effectiveness (RBE) of a therapeutic 80-MeV proton beam compared to a gamma ray of ^<6O>Co. The RBE of the 80 MeV proton was 1.4-1.6 at the Bragg peak, 1.1 at the spread-out Bragg peak.The time course of a tumor growth was measured after a single irradiation of the proton beam and/or a single intraperitoneal administration of AVE8062. The proton irradiation provided large antitumor effects such as a tumor volume reduction and a tumor growth delay (TGD) depending on the proton absorbed dose ( 15 or 30 Gy ), while there were not significant differences in TGD between the AVE8062 administration groups ( 5 or 10 mg/kg) and an unirradiated control. The proton irradiation in combination with the AVE8062 administration resulted in the almost same TGD as the monotherapy of proton irradiation. The present results suggest that it is important to optimize the protocol for the combined treatment to provide a larger antitumor effect compared to the monotherapy.