Comparison of optical and power Doppler ultrasound imaging for non-invasive evaluation of arsenic trioxide as a vascular disrupting agent in tumors

• Published in: PloS one Vol. 7; no. 9; p. e46106
• Main Authors: Alhasan, Mustafa K, Liu, Li, Lewis, Matthew A, Magnusson, Jennifer, Mason, Ralph P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-09-2012; Public Library of Science (PLoS)
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Apoptosis; Arsenic; Arsenic trioxide; Arsenicals - therapeutic use; Biology; Bioluminescence; Blood flow; Blood Vessels - drug effects; Brain; Brain cancer; Brain Neoplasms - blood supply; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Brain tumors; Breast cancer; Breast Neoplasms - blood supply; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer therapies; Care and treatment; Cell culture; Cell Line, Tumor; Chemical properties; Clinical trials; Doppler effect; Female; Fluorescence; Humans; Imaging; Light emission; Luciferase; Luciferin; Male; Medical research; Medicine; Mice; Mice, Nude; Movement disorders; Neoplasm Transplantation - diagnostic imaging; Neuroimaging; Optical Imaging - methods; Oxides - therapeutic use; Perfusion; Prostate; Prostatic Neoplasms - blood supply; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; R&D; Recovery; Research & development; Risk factors; Solid tumors; Tumors; Ultrasonic imaging; Ultrasonography, Doppler - methods; Ultrasound; Ultrasound imaging; Xenografts; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046106

Small animal imaging provides diverse methods for evaluating tumor growth and acute response to therapy. This study compared the utility of non-invasive optical and ultrasound imaging to monitor growth of three diverse human tumor xenografts (brain U87-luc-mCherry, mammary MCF7-luc-mCherry, and prostate PC3-luc) growing in nude mice. Bioluminescence imaging (BLI), fluorescence imaging (FLI), and Power Doppler ultrasound (PD US) were then applied to examine acute vascular disruption following administration of arsenic trioxide (ATO).During initial tumor growth, strong correlations were found between manual caliper measured tumor volume and FLI intensity, BLI intensity following luciferin injection, and traditional B-mode US. Administration of ATO to established U87 tumors caused significant vascular shutdown within 2 hrs at all doses in the range 5 to 10 mg/kg in a dose dependant manner, as revealed by depressed bioluminescent light emission. At lower doses substantial recovery was seen within 4 hrs. At 8 mg/kg there was >85% reduction in tumor vascular perfusion, which remained depressed after 6 hrs, but showed some recovery after 24 hrs. Similar response was observed in MCF7 and PC3 tumors. Dynamic BLI and PD US each showed similar duration and percent reductions in tumor blood flow, but FLI showed no significant changes during the first 24 hrs.The results provide further evidence for comparable utility of optical and ultrasound imaging for monitoring tumor growth, More specifically, they confirm the utility of BLI and ultrasound imaging as facile assays of the vascular disruption in solid tumors based on ATO as a model agent.