Acute Effects of Vascular Modifying Agents in Solid Tumors Assessed by Noninvasive Laser Doppler Flowmetry and Near Infrared Spectroscopy

Abstract

The potential of noninvasive laser Doppler flowmetry (LDF) and near infrared spectroscopy (NIRS) to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (∼200 mm3) in the rear foot of CDF1 mice were treated with flavone acetic acid (FAA, 150 mg/kg), 5,6-dimethylxanthenone-4acetic acid (DMXAA, 20 mg/kg), combretastatin A-4 disodium phosphate (CAMP, 250 mg/kg), hydralazine (HDZ, 5 mg/kg), or nicotinamide (NTA, 500 mg/kg). Tumor perfusion before and after treatment was evaluated by noninvasive LDF, using a 41°C heated custombuilt LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by MRS, using light guide coupled reflectance measurements at 800±10 nm. FAA, DMXAA, CAMP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CAMP caused no change in the tumor blood volume, indicating that the mechanism of action of CAMP was vascular shut down with the blood pool trapped in the tumor. NTA caused no change in either tumor perfusion or tumor blood volume. We conclude that noninvasive LDF and MRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume.

Keywords

• laser Doppler flow (LDF)
• near infrared spectroscopy (NIRS)
• combretastatin A4 disodium phosphate
• hydralazine
• C3H mouse mammary carcinoma