Detection of disseminated breast cancer growth and treatment response using non-invasive bioluminescence imaging.

Academic Article

Abstract

  • 742 Background: TRA-8, a mouse anti-human DR5 monoclonal antibody induces apoptosis in TRAIL-sensitive tumor cells. However no non-invasive method is available to monitor the treatment effects on disseminated cancer. We report a non-invasive and sensitive BI technology to determine the efficacy of combined treatment of TRA-8 and Adriamycin on disseminated breast cancer in animal model. METHODS: Human breast cancer cell line 2LMP, a subclone of MDA-MB-231, was transfected with adeno associated virus encoding luciferase (AAV-luc). A stable luciferase-positive cell line was established by screening. Two groups (5/group) of athymic female nude mice were used. Four sites (liver, spleen, chest cavity and peritoneum) of each mouse were injected with luciferase-positive 2LMP cells (0.25x106/site). After 7 days, BI revealed disseminated tumor sites; one group of mice was injected i.v. with 150 μg TRA-8 and 6 mg/kg Adriamycin, and the 2nd group of mice did not receive any treatment. All treatments were given 2X/wk for 3 wks. Mice were imaged over time with an IVIS-100 Xenogen imaging system and tumor mass was estimated from ventral, dorsal, left and right lateral views by measuring light transmitted from the luciferase positive tumors. RESULTS: All untreated mice died by day 21 with 4-6 fold increases in bioluminescence and extensive metastasis, including bone. Treated mice had a dramatic decrease in bioluminescence to 15-20% of day 7 values that persisted for 45 days and then began a progressive regrowth of tumor (increasing bioluminescence) in multiple sites. Dissemination of breast cancer was detected by BI and confirmed by dissection. In all untreated mice, numerous tumor nodules were detected in lungs, heart, pleural space, bones including ribs and spine, diaphragm, esophagus and pericardium, liver, spleen, stomach, kidneys, ovaries, uterus, and peritoneal membrane. CONCLUSIONS: BI demonstrated high sensitivity for non-invasive detection and treatment monitoring of disseminated breast tumors in mice. Combination therapy with TRA-8 and Adriamycin was highly effective in the regression of disseminated breast cancer in this animal model. No significant financial relationships to disclose.
  • Pubmed Id

  • 10722793
  • Author List

  • Chaudhuri TR; Cao Z; Ponnazhagan S; Stargel A; Simhadri PL; Zhou T; Lobuglio AF; Buchsbaum DJ; Zinn KR
  • Start Page

  • 742
  • Volume

  • 22
  • Issue

  • 14_suppl