Quantitative contrast enhanced ultrasound and CT assessment of tumor response to antiangiogenic therapy in rats.
Contrast-enhanced computed tomography (CECT) and contrast-enhanced destruction-replenishment subharmonic ultrasound (CEDRSU) were used to quantify blood flow and tumor viability during antiangiogenic therapy. SU11657 or placebo was administered to R3230AC tumor-baring rats over a two-week period. CEDRSU vascular volume (ASI) and volume flow (VF) and CECT perfusion (PR) and permeability (PM) measurements were made on day 0, 7 and 14. The percent change in imaging parameters was calculated between day 0 and 7 and 14. Serum drug level (SDL) was compared with imaging parameters. Imaging estimates of tumor viability were compared with histology images on day 14. The percent change in imaging measures for control and treated groups were significantly different on day 7(ASI, p = 0.02; VF, p = 0.008, PR, p = 0.0007; PM, p = 0.003) and 14 (ASI, p = 0.0004; VF, p = 0.002, PR, p = 0.003; PM, p = 0.005). Imaging identified animals with lower SDLs as having higher tumor vascularity and flow. Spatial estimates of tumor viability correlated with histology (CEDRSU, r(2) = 0.92, p << 0.001; CT, r(2) = 0.86, p << 0.001). CEDRSU and CECT provide measures of blood flow and viability in tumors during antiangiogenic therapy. Tumors with higher flow were identified in animals with lower SDL. SU11657 treatment results in decreased tumor flow and viability.
Pollard
Rachel E
RE
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. repollard@ucdavis.edu
Broumas
Amy R
AR
Wisner
Erik R
ER
Vekich
Sylvia V
SV
Ferrara
Katherine W
KW
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D020533:Angiogenesis Inhibitors / Q000097:blood / Q000627:therapeutic use*; D000818:Animals; D001810:Blood Volume / Q000502:physiology; D005260:Female; D007089:Image Enhancement / Q000379:methods; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D009368:Neoplasm Transplantation / Q000379:methods; D009930:Organic Chemicals / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012039:Regional Blood Flow; D014057:Tomography, X-Ray Computed / Q000379:methods; D014463:Ultrasonography
D020533:Angiogenesis Inhibitors; D009930:Organic Chemicals; C474557:SU 11657; D020794:Receptor Protein-Tyrosine Kinases