Correlation of beta-camera imaging and immunohistochemistry in radioimmunotherapy using90Y-labeled monoclonal antibodies in ovarian cancer animal models |
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Authors: | Kairemo Kalevi J A Ljunggren Kaj Wahlström Torsten Stigbrand Torgny Strand Sven-Erik |
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Institution: | 1.Department of Clinical Chemistry, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290, Helsinki, Finland ;3.Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290, Helsinki, Finland ;2.Department of Radiation Physics, University of Lund, Lund, Sweden ;4.Department of Medical Biochemistry, University of Ume?, Sweden ; |
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Abstract: | Tumor stroma contains much fibrin and monoclonal antifibrin antibody targeting is possible in tumors. In this study, nude
mouse human ovarian carcinoma xenograft specimens were investigated after treatment with90Y-labeled monoclonal antifibrin antibody Fab fragment or with90Y-labeled OC125-monoclonal antibody F(ab′)2 fragments. The mice received the radioimmunotherapy activity either intratumorally, intraperitoneally, or intravenously.
Beta-camera imaging (BCI) is a novel device for studying activity distribution in tissue specimens and, together with immunohistochemistry
(IHC) with OC125, antifibrin, anticarcinoembryonic antigen, anti-cytokeratin, and anti-placental alkaline phosphatase antibodies,
was used for correlation of activity distribution of tissue specimens. These results were in concordance: Antigen distribution
measured with IHC and radioactivity distribution were similar with the same antibodies, antifibrin, and OC125: However, these
antigens demonstrated rather different distribution. Tissue studies revealed that activity was concentrated also in the necrotic
tumor tissue, indicating that cell death was also caused by radiation. Differences in the tumor cell morphology were observed
using different routes of administration. With BCI, it is possible to quantitate activities in frozen sections (microdosimetry),
and these results were in concordance with absolute activities as measured by tissue sampling and well-counting. Three-dimensional
reconstruction of tissue slices combined with radioactivity distribution measured with BCI allows estimation of total absorbed
radiation dose in tumor after an appropriate dose planning. |
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Keywords: | Monoclonal antibodies radioimmunotherapy ovarian cancer 90Y fibrin xenograft nude mice CA125 immunohistochemistry beta-camera imaging |
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