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

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

*Corresponding author for this work

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2 Citations (Web of Science)

Abstract

Aim of the Study. To compare Annexin V-based optical apoptosis imaging with the assessment of the glucose metabolism using F-18-FDG-PET/CT for monitoring the response to cytotoxic (carboplatin) and anti-angiogenic (sunitinib) therapy. Methods. For apoptosis imaging, the near-infrared probe Annexin Vivo750 was used in combination with fluorescence molecular tomography and microcomputed tomography (FMT/mu CT). Glucose metabolism was assessed using F-18-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 F-18-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 (F-18-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.

Original languageEnglish
Article number6676337
Number of pages11
JournalContrast Media & Molecular Imaging
Volume2021
DOIs
Publication statusPublished - 13 Apr 2021

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