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7. Change of Apoptosis and Glucose Metabolism in Lung Cancer Xenografts during Cytotoxic and Anti-Angiogenic Therapy Assessed by Annexin V Based Optical Imaging and 18F-FDG-PET/CT

Author

Gross, Jasmin, primary, Palmowski, Karin, additional, Doleschel, Dennis, additional, Rix, Anne, additional, Gremse, Felix, additional, Verburg, Frederic, additional, Mottaghy, Felix M., additional, Kiessling, Fabian, additional, Lederle, Wiltrud, additional, and Palmowski, Moritz, additional

Published
2021
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9. Hybrid μCT-FMT imaging and image analyses

Author

Gremse, Felix, Doleschel, Dennis, Zafarnia, Sara, Babler, Anne, Jahnen-Dechent, Willi, Lammers, Twan, Lederle, Wiltrud, Kiessling, Fabian, Faculty of Science and Technology, and Biomaterials Science and Technology

Subjects
METIS-315268, IR-99946
Abstract

We describe a protocol for hybrid imaging, combining fluorescence-mediated tomography (FMT) with micro computed tomography (µCT). After fusion and reconstruction, we perform interactive organ segmentation to extract quantitative measurements of the fluorescence distribution. Fluorescence-mediated tomography (FMT) enables longitudinal and quantitative determination of the fluorescence distribution in vivo and can be used to assess the biodistribution of novel probes and to assess disease progression using established molecular probes or reporter genes The combination with an anatomical modality, e.g., micro computed tomography (µCT), is beneficial for image analysis and for fluorescence reconstruction. We describe a protocol for multimodal µCT-FMT imaging including the image processing steps necessary to extract quantitative measurements. After preparing the mice and performing the imaging, the multimodal data sets are registered. Subsequently, an improved fluorescence reconstruction is performed, which takes into account the shape of the mouse. For quantitative analysis, organ segmentations are generated based on the anatomical data using our interactive segmentation tool. Finally, the biodistribution curves are generated using a batch-processing feature. We show the applicability of the method by assessing the biodistribution of a well-known probe that binds to bones and joints.

Published
2015

11. Erythropoietin Improves the Accumulation and Therapeutic Effects of Carboplatin by Enhancing Tumor Vascularization and Perfusion

Author

Doleschel, Dennis, primary, Rix, Anne, additional, Arns, Susanne, additional, Palmowski, Karin, additional, Gremse, Felix, additional, Merkle, Ruth, additional, Salopiata, Florian, additional, Klingmüller, Ursula, additional, Jarsch, Michael, additional, Kiessling, Fabian, additional, and Lederle, Wiltrud, additional

Published
2015
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13. Change of Apoptosis and Glucose Metabolism in Lung Cancer Xenografts during Cytotoxic and Anti-Angiogenic Therapy Assessed by Annexin V Based Optical Imaging and 18 F-FDG-PET/CT.

Author

Gross J, Palmowski K, Doleschel D, Rix A, Gremse F, Verburg F, Mottaghy FM, Kiessling F, Lederle W, and Palmowski M

Subjects
Angiogenesis Inhibitors pharmacology, Animals, Annexin A5 chemistry, Annexin A5 pharmacology, Apoptosis drug effects, Cell Proliferation drug effects, Fluorodeoxyglucose F18 pharmacology, Glucose metabolism, Heterografts, Humans, Lung Neoplasms pathology, Mice, Lung Neoplasms diagnostic imaging, Lung Neoplasms drug therapy, Optical Imaging, Positron Emission Tomography Computed Tomography
Abstract

Methods: For apoptosis imaging, the near-infrared probe Annexin Vivo750 was used in combination with fluorescence molecular tomography and microcomputed tomography (FMT/ µ CT). Glucose metabolism was assessed using 18 F-FDG-PET/CT. Five groups of nude mice bearing lung cancer xenografts (A549) were investigated: (i) untreated controls and two groups after (ii) cytotoxic (carboplatin) or (iii) anti-angiogenic (sunitinib) treatment for four and nine days, respectively. Imaging data were validated by immunohistochemistry., Results: In response to carboplatin treatment, an inverse relation was found between the change in glucose metabolism and apoptosis in A549 tumors. Annexin Vivo showed a continually increasing tumor accumulation, while the tumor-to-muscle ratio of 18 F-FDG continuously decreased during therapy. Immunohistochemistry revealed a significantly higher tumor apoptosis ( p =0.007) and a minor but not significant reduction in vessel density only at day 9 of carboplatin therapy. Interestingly, during anti-angiogenic treatment there was an early drop in the tumor-to-muscle ratio between days 0 and 4, followed by a subsequent minor decrease ( 18 F-FDG tumor-to-muscle-ratio: 1.9 ± 0.4; day 4: 1.1 ± 0.2; day 9: 1.0 ± 0.2; p =0.021 and p =0.001, respectively). The accumulation of Annexin Vivo continuously increased over time (Annexin Vivo: untreated: 53.7 ± 36.4 nM; day 4: 87.2 ± 53.4 nM; day 9: 115.1 ± 103.7 nM) but failed to display the very prominent early induction of tumor apoptosis that was found by histology already at day 4 (TUNEL: p =0.0036) together with a decline in vessel density (CD31: p =0.004), followed by no significant changes thereafter., Conclusion: Both molecular imaging approaches enable visualizing the effects of cytotoxic and anti-angiogenic therapy in A549 tumors. However, the early and strong tumor apoptosis induced by the anti-angiogenic agent sunitinib was more sensitively and reliably captured by monitoring of the glucose metabolism as compared to Annexin V-based apoptosis imaging., Competing Interests: All authors declare that there are no conflicts of interest., (Copyright © 2021 Jasmin Gross et al.)

Published
2021
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