Sonia Lavisse, Presenter: Nothing to Disclose

Valerie Rouffiac PhD, Abstract Co-Author: Nothing to Disclose

Nicolas Elie PhD, Abstract Co-Author: Nothing to Disclose

Pascale Lejeune PhD, Abstract Co-Author: Nothing to Disclose

Marie-Christine Bissery PhD, Abstract Co-Author: Nothing to Disclose

Nathalie Brigitte Lassau MD, PhD, Abstract Co-Author: Nothing to Disclose

AVE8062A is an analog of Combretastatin A4 showing potent antitumor efficacy by inhibiting tubulin polymerization. Although its in vivo efficacy is well demonstrated in animal models, there is a need to link the drug efficacy to its effect on the tumor functional vascularization and perfusion. In the US modality, widely used to evaluate early treatment efficacy in human trials, new modes involving the nonlinear properties of some contrast agents have been recently available and are able to provide a precise access to the tumor perfusion and quantification of the contrast uptake kinetics. In this study, the effect of AVE8062A on tumor hemodynamics was studied using DCE-US.

The drug was administred to 40 mice bearing established B16 melanoma. US examinations were performed on a Aplio machine (Toshiba) associated to a perfusion quantification software (CHI-Q). Animals were imaged before and at different times post AVE8062 injection (5, 15 min, 1, 6 and 24h). The protocol was performed with the quantification of the 1) intratumoral vascularization and 2) US contrast uptake within the tumor (Vascular Recognition Imaging) after Sonovue injection (Bracco). Peak intensity (PI), time-to-peak intensity (TPI) and mean transit time (MTT) parameters were extracted from the time intensity modelized curves expressed in raw data. For histological evaluation of vascularization and necrosis, tumors were sampled at the different time points.

A significant 35% decrease of the intratumoral vessel number was shown as early as 15 min post injection. The decrease was maximal (44%) 6 hours post treatment. Following contrast agent injection, a 5.4 dB (17%) decrease in PI was quantified after 1 hour and reached 16.4 dB (50%) at 6 h.TPI and MTT parameters showed significant modification only at 6h.

Doppler US, in combination with a perfusion software, is a sensitive and noninvasive technique that was able to show that AVE8062A induces a major decrease in tumor perfusion with a maximal effect by 6 hours.

DCE-US method can be used to evaluate functional consequences of anti-vascular agents therapy and is currently under investigation in an on going AVE8062A clinical trial

Lavisse, S, Rouffiac, V, Elie, N, Lejeune, P, Bissery, M, Lassau, N, Early Evaluation of the Vascular Targeting Agent AVE8062A in Melanoma Tumor Bearing Mice Using Dynamic Contrast-enhanced Ultrasonography (DCE-US).  Radiological Society of North America 2006 Scientific Assembly and Annual Meeting, November 26 - December 1, 2006 ,Chicago IL. http://archive.rsna.org/2006/4431351.html