Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy.
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 (approximately 200 mm(3)) in the rear foot of CDF1 mice were treated with flavone acetic acid (FAA, 150 mg/kg), 5,6-dimethylxanthenone-4-acetic acid (DMXAA, 20 mg/kg), combretastatin A-4 disodium phosphate (CA4DP, 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 degrees C heated custom-built LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by NIRS, using light guide coupled reflectance measurements at 800+/-10 nm. FAA, DMXAA, CA4DP, 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. CA4DP caused no change in the tumor blood volume, indicating that the mechanism of action of CA4DP 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 NIRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume.
Kragh
Michael
M
Institute of Molecular Pathology, Panum Institute, University of Copenhagen, 11 Frederik V Vej, DK-2200 Copenhagen, Denmark.
Quistorff
Bjørn
B
Horsman
Michael R
MR
Kristjansen
Paul E G
PE
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use; D006830:Hydralazine / Q000627:therapeutic use; D017078:Laser-Doppler Flowmetry / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic; D009536:Niacinamide / Q000627:therapeutic use; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013267:Stilbenes / Q000627:therapeutic use; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000627:therapeutic use; D014966:Xanthenes / Q000627:therapeutic use; D044004:Xanthones
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D013267:Stilbenes; D014665:Vasodilator Agents; D014966:Xanthenes; D044004:Xanthones; C066668:vadimezan; D009536:Niacinamide; D006830:Hydralazine; C049328:flavone acetic acid; C058728:fosbretabulin