title: Dose-response relationship of ultrasound contrast agent in an in vivo murine melanoma model.
abstract: Many factors affect the sensitivity and reliability of tumor vasculature assessment at the small doses of contrast agent necessary for imaging mice. In this study we investigate the dose-response relationship of ultrasound contrast agent for a minimal exposure power Doppler technique (minexPD) in a murine melanoma model. K1735 murine melanomas grown in 25 C3H/HeN mice were imaged by power Doppler ultrasound using different doses of contrast agents, Optison(R) and Definity(R). Six mice were treated with an antivascular agent, combretastatin A4-phosphate (CA4P), and imaged before and after treatment. The color-weighted fractional area (CWFA) of the peak-enhanced image was measured to assess tumor perfusion on a relative scale of 0 to 100. CWFA increased logarithmically with dose (R(2)=0.97). Treatment with CA4P resulted in pronounced reduction in tumor perfusion 2 h after contrast injection, but perfusion recovered in the tumor periphery after 2 days. CWFA was significantly different between pre- and post-treatment for all doses at 2 h and 2 days (p < 0.05, respectively). There was no significant difference detectable between the two contrast agents, Optison(R) and Definity(R) (p = 0.46). In vivo tumor enhancement in mice increases as logarithmic function with dose. Although the extent of enhancement is dose dependent, the difference between pre- and post-therapy enhancement is relatively unchanged and uniform at varying doses. The two contrast agents tested in this study performed equally well. These results suggest that quantitative contrast-enhanced power Doppler imaging is an effective method for monitoring therapy response of tumors in mice.
authors: Department of Clinical Studies, Philadelphia, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey Street, Philadelphia, PA 19104, USA. gseiler@vet.upenn.edu
authors: Gabriela S
authors: GS
authors: Seiler
authors: Lisa S
authors: LS
authors: Ziemer
authors: Susan
authors: S
authors: Schultz
authors: William M F
authors: WM
authors: Lee
authors: Chandra M
authors: CM
authors: Sehgal
mesh_terms: D000418:Albumins / Q000008:administration & dosage*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D003287:Contrast Media / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005466:Fluorocarbons / Q000008:administration & dosage*; D007091:Image Processing, Computer-Assisted; D008546:Melanoma, Experimental / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000188:drug therapy; D051379:Mice; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000188:drug therapy; D013267:Stilbenes / Q000494:pharmacology; D018608:Ultrasonography, Doppler
chemical_list: D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; C099458:FS 069; D005466:Fluorocarbons; D013267:Stilbenes; C058728:fosbretabulin; C042852:perflutren