Monitoring Cell Death in Regorafenib-Treated Experimental Colon Carcinomas Using Annexin-Based Optical Fluorescence Imaging Validated by Perfusion MRI

Kazmierczak, Philipp M.; Burian, Egon; Eschbach, Ralf; Hirner-Eppeneder, Heidrun; Moser, Matthias; Havla, Lukas; Eisenblaetter, Michel; Reiser, Maximilian F.; Nikolaou, Konstantin und Cyran, Clemens C. (2015): Monitoring Cell Death in Regorafenib-Treated Experimental Colon Carcinomas Using Annexin-Based Optical Fluorescence Imaging Validated by Perfusion MRI.
In: PLOS ONE 10(9), e0138452

Abstract

Objective To investigate annexin-based optical fluorescence imaging (OI) for monitoring regorafenib-induced early cell death in experimental colon carcinomas in rats, validated by perfusion MRI and multiparametric immunohistochemistry. Materials and Methods Subcutaneous human colon carcinomas (HT-29) in athymic rats (n = 16) were imaged before and after a one-week therapy with regorafenib (n = 8) or placebo (n = 8) using annexin-based OI and perfusion MRI at 3 Tesla. Optical signal-to-noise ratio (SNR) and MRI tumor perfusion parameters (plasma flow PF, mL/100mL/min;plasma volume PV,%) were assessed. On day 7, tumors underwent immunohistochemical analysis for tumor cell apoptosis (TUNEL),proliferation (Ki-67),and microvascular density (CD31). Results Apoptosis-targeted OI demonstrated a tumor-specific probe accumulation with a significant increase of tumor SNR under therapy (mean Delta +7.78 +/- 2.95, control: -0.80 +/- 2.48, p = 0.021). MRI detected a significant reduction of tumor perfusion in the therapy group (mean Delta PF -8.17 +/- 2.32 mL/100 mL/min, control -0.11 +/- 3.36 mL/100 mL/min, p = 0.036). Immunohistochemistry showed significantly more apoptosis (TUNEL;11392 +/- 1486 vs. 2921 +/- 334, p = 0.001),significantly less proliferation (Ki-67;1754 +/- 184 vs. 2883 +/- 323, p = 0.012),and significantly lower microvascular density (CD31;107 +/- 10 vs. 182 +/- 22, p = 0.006) in the therapy group. Conclusions Annexin-based OI allowed for the non-invasive monitoring of regorafenib-induced early cell death in experimental colon carcinomas, validated by perfusion MRI and multiparametric immunohistochemistry.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Institut für Diagnostische und Interventionelle Neuroradiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1932-6203
• Sprache: Englisch