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EFSUMB EUROPEAN FEDERATION OF SOCIETIES FOR ULTRASOUND IN MEDICINE AND BIOLOGY ‘Building a European Ultrasound Community’ Young Investigator’s Award WFUMB 2011 VIENNA AUSTRIA 28 August 2011 13.50 – 15.45 10 minutes each for presentation plus 3 minutes discussion

Use of VEGF-RECEPTOR TARGETED MICROBUBBLES (BR55) for the early ultrasound evaluation of response to antiangiogenic treatment in a xenograFt model of hepatocarcinoma 1

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M. Baron Toaldo , V. Salvatore , C. Palamà , S. Marinelli , M. Milazzo , L. Gramantieri , M. Cipone , 2 2 L. Bolondi , F. Piscaglia 1

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Department of Veterinary medical sciences Departement of Clinical Medicine Centro di Ricerca Biomedica Applicata University of Bologna

ABSTRACT Aim: To evaluate the early response to treatment to an antiangiogenetic drug (sorafenib) in a heterotopic murine model of hepatocellular carcinoma (HCC) using ultrasonographic molecular imaging. Material and Methods: the xenographt model was established injecting a suspension of HuH7 cells subcutaneously in 19 nude mice. When tumors reached a mean diameter of 5-10 mm, they were divided in two groups (treatment and vehicle). The treatment group received sorafenib (62 mg/kg) by daily oral gavage for 14 days. Molecular imaging was performed using contrast enhanced ultrasound (CEUS), by injecting into the mouse venous circulation a suspension of VEGFR-2 targeted microbubbles (BR55, kind gift of Bracco Research, Geneve, Switzerland). Video clips were acquired for 6 minutes, then microbubbles (MBs) were destroyed by a high mechanical index (MI) impulse, and another minute was recorded to evaluate residual circulating MBs. The US protocol was repeated at day 0,+2,+4,+7, and +14 from the beginning of treatment administration. Video clips were analyzed using a dedicated software (Sonotumor, Bracco Research) to quantify the signal of the contrast agent. Time/intensity curves were obtained and the difference of the mean MBs signal before and after high MI impulse (Differential Targeted Enhancement-dTE) was calculated. dTE represents a numeric value in arbitrary units proportional to the amount of bound MBs. At day +14 mice were euthanized and the tumors analyzed for VEGFR-2, pERK, and CD31 tissue levels using western blot analysis. Results: dTE values decreased from day 0 to day +14 both in treatment and vehicle groups, and they were statistically higher in vehicle group than in treatment group at day +2, at day +7, and at day +14. With respect to the degree of tumor volume in , treatment group was divided in two sub-groups, non0%). dTE values at day 0 (immediately before treatment start) were higher in non-responders than in responders group, with statistical difference at day 2. While dTE values were higher in the fast growth group than in the slow growth group only at day 0. A significant positive correlation was found between VEGFR-2 tissue levels and dTE values, confirming that level of BR55 tissue enhancement reflects the amount of tissue VEGF receptor. Conclusions: the present findings show that, at least in murine experimental models, CEUS with BR55 is feasable and appears to be a useful tool in the prediction of tumor growth and response to Sorafenib treatment in xenograft HCC.

YIA 2011 - abstract - toaldo  

YIA entry for WFUMB 2011

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