Bioluminescence Image as a Quantitative Imaging Biomarker for Preclinical Evaluation of Cryoablation in a Murine Model

J Vasc Interv Radiol. 2018 Jul;29(7):1034-1040. doi: 10.1016/j.jvir.2018.03.013. Epub 2018 Jun 5.

Abstract

Purpose: To employ bioluminescence imaging (BLI) as a quantitative imaging biomarker to assess preclinical evaluation of cryoablation in a murine model.

Materials and methods: In vitro, Colon26-Luc (C26-Luc) cells were seeded at 6 different concentrations in 35-mm dishes. These were divided into 6 groups: group 0 (G0), a control group without treatment; and groups 1-5 (G1-G5) according to the number of freeze-thaw cycles, with each cycle consisting of freezing at -80°C for 10 min followed by thawing at room temperature for 5 minutes. BLI and flow-cytometric analysis were performed after cryotherapy. In vivo, 20 tumor-bearing mice with C26-Luc cells were divided into 4 groups: group 0 (G0), a control group; and groups 1-3 (G1-G3) according to the number of freeze-thaw cycles. Each cryoablation procedure was performed for 30 seconds with liquid nitrogen (-170°C) applied with cotton-tipped applicators. BLI was acquired at 6 hours and 1, 3, and 7 days after treatments.

Results: In vitro, BLI signal showed a negative correlation with the number of freeze-thaw cycles (r = -0.86, P = .02). In vivo, there was no difference in tumor volume at 1 day after cryoablation among all groups, but the BLI signals were significantly different between G0 and G2/G3 (P = .03 and P = .02, respectively) and between G1 and G3 (P = .04). BLI signals reflected tumor growth speed and survival ratio.

Conclusions: This study demonstrates the direct validation of BLI as a quantitative tool for the early assessment of therapeutic effects of cryoablation.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / diagnostic imaging
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery*
  • Cryosurgery*
  • Luminescent Measurements
  • Male
  • Mice, Inbred BALB C
  • Optical Imaging / methods*
  • Predictive Value of Tests
  • Reproducibility of Results
  • Time Factors
  • Tumor Burden