Rachel Schor-Bardach MD, Abstract Co-Author: Nothing to Disclose

David C. Alsop PhD, Abstract Co-Author: Nothing to Disclose

Ivan Pedrosa MD, Abstract Co-Author: Nothing to Disclose

Stephanie Solazzo MA, Abstract Co-Author: Nothing to Disclose

Robert E. Lenkinski PhD, Abstract Co-Author: Nothing to Disclose

S. Nahum Goldberg MD, Presenter: Medical Advisory Board, Tyco Healthcare (Valleylab), Boulder, CO Research support, Tyco Healthcare (Valleylab), Boulder, CO Research support, RITA Medical Systems, Inc, Freemont, CA

To determine whether ASL MR imaging can detect early changes in therapeutic response to anti-angiogenic, sorafenib therapy in an animal tumor model.

Three human renal cell carcinoma xenographs were implanted in 28 nude mice including: Caki-1 (sorafenib resistant, n=6), A498 (sorafenib sensitive, n=6), and 786-0 (early response followed by rapid development of resistance by day 5, n=15). Animals received 80mg/kg of Sorafenib qd beginning at 12mm diameter. ASL imaging (2mm slice thickness at greatest axial diameter) was performed at baseline and day 14, with additional time points performed for 786-0 at days 3-9. ASL values were analyzed quantitatively (ie. using mean blood flow values) and qualitatively (ie. comparing spatial serial blood flow (BF) changes in the generated perfusion maps) and compared to the histopathologic reference standard for viability.

Baseline flow was 67.4±15.2(ml/100mg/min) for A498, 78.1±29.6 for 786-0 and 10.3±9.5 for Caki-1. Treated Caki-1 showed no significant change in blood flow on day 14 (15.6±7.5), whereas BF decreased variably in all treated A498 (39.3±22.6, 41.7% mean decrease). 786-0 showed decreased mean blood flow on day 3 (22.5±10.2, 71.2% decrease), with no significant further alterations in mean blood flow observed thereafter (10.9±15.5 - 31.8±28.8 days 5-14, p>0.10). Qualitatively, no significant change in ASL signal or pathologic appearance was seen after treatment for Caki-1. Day 14 A498 and day 5-9 786-0 had central loss of ASL signal, with patchy return of signal beyond day 9 in 786-0. Although BF change was variable, its extent corresponded tightly to histopathologic appearance (r2>0.7). High signal regions correlate to viable tumor, with zones of absent or diminished signal (i.e. less than 2 ml/100mg/min) represent necrosis.

ASL imaging provides important information regards tumor viability in lines that respond to sorafenib as manifest by tight radiologic pathologic correlation to induced intratumoral necrosis.

If further characterized and validated, ASL MRI may provide additional useful information upon which to base therapeutic decisions for patients with well-perfused tumors.

Schor-Bardach, R, Alsop, D, Pedrosa, I, Solazzo, S, Lenkinski, R, Goldberg, S, Arterial Spin Labeling (ASL) MR Perfusion Provides Excellent Radiologic-Pathologic Correlation for Monitoring Responses to Antiangiogenic Therapy in Renal Cell Cancer Animal Models.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5009447.html