Quantitative Analysis of Chemotherapeutic Effects in Tumors Using In Vivo Staining and Correlative Histology
Choi, Heung Kook
Choi, Hyun Ju
Ntziachristos, VasilisNote: Order does not necessarily reflect citation order of authors.
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CitationChoi, Heung Kook, Doreen Yessayan, Hyun Ju Choi, Eyk Schellenberger, Alex Bogdanov, Lee Josephson, Ralph Weissleder, and Vasilis Ntziachristos. 2005. “Quantitative Analysis of Chemotherapeutic Effects in Tumors Using In Vivo Staining and Correlative Histology.” Cellular Oncology : the Official Journal of the International Society for Cellular Oncology 27 (3): 183-190. doi:10.1155/2005/791936. http://dx.doi.org/10.1155/2005/791936.
AbstractAims: To microscopically analyze the chemotherapeutic response of tumors using in vivo staining based on an annexinV-Cy5.5 probe and independently asses their apoptotic count using quantitative histological analysis. Methods:: Lewis Lung Carcinomas cells, that are sensitive (CS-LLC) and resistant (CR-LLC) to chemotherapy were implanted in nude mice and grown to tumours. Mice were treated with cyclophosphamide and injected with a Cy5.5-annexinV fluorescent probe. In vivo imaging was performed using Fluorescence Molecular Tomography. Subsequently tumours were excised and prepared for histology. The histological tumour sections were stained for apoptosis using a terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. A minimum of ten tissue sections were analyzed per tumour for apoptosis quantification by TUNEL staining and corresponding Cy5.5 distribution. Results:: We detected higher levels of apoptosis and corresponding higher levels of Cy5.5 fluorescence in the CS-LLC vs. the CR-LLC tumours. The cell count rate on CS-LLC sections over CR-LLC was found to be ∼2 :1 where the corresponding area observed on Cy5.5 distribution measurements revealed a ∼1.7 :1 ratio of CS-LLC over CR-LLC. These observations are consistent with the higher apoptotic index expected from the CS-LLC cell line. Conclusions:: Quantitative analysis of histological slices revealed higher fluorescence and higher apoptotic count in the CS-LLC tumour images compared to the CR-LLC tumour images. These observations demonstrate that the annexinV-Cy5.5 probe sensed the chemotherapeutic effect of cyclophospamide and further confirmed in vivo FMT measurements.
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