Evaluation of apoptosis imaging biomarkers in a genetic model of cell death
Authors
Vassileva, VStribbling, M
Barnes, C
Carroll, L
Braga, M
Abrahams, J
Heinzmann, K
Haegeman, C
MacFarlane, M
Simpson, Kathryn L
Dive, Caroline
Honeychurch, Jamie
Illidge, Timothy M
Aboagye, O
Affiliation
Hospital for Children and Adolescents; Division for Stem Cell Transplantation and Immunology, University Hospital Frankfurt, Frankfurt, GermanyIssue Date
2019
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PURPOSE: We have previously developed the caspase-based radiotracer, 18F-ICMT-11, for PET imaging to monitor treatment response. We further validated 18F-ICMT-11 specificity in a murine melanoma death-switch tumour model with conditional activation of caspase-3 induced by doxycycline. METHODS: Caspase-3/7 activity and cellular uptake of 18F-ICMT-11, 18F-ML-10 and 18F-FDG were assessed in B16ova and B16ovaRevC3 cells after death-switch induction. Death-switch induction was confirmed in vivo in xenograft tumours, and 18F-ICMT-11 and 18F-ML-10 biodistribution was assessed by ex vivo gamma counting of select tissues. PET imaging was performed with 18F-ICMT-11, 18F-ML-10 and 18F-FDG. Caspase-3 activation was confirmed by immunohistochemistry. RESULTS: Significantly increased caspase-3/7 activity was observed only in B16ovaRevC3 cells after death-switch induction, accompanied by significantly increased 18F-ICMT-11 (p?<?0.001) and 18F-ML-10 (p?<?0.05) and decreased 18F-FDG (p?<?0.001) uptake compared with controls. B16ova and B16ovaRevC3 tumours had similar growth in vivo; however, B16ovaRevC3 growth was significantly reduced with death-switch induction (p?<?0.01). Biodistribution studies showed significantly increased 18F-ICMT-11 tumour uptake following death-switch induction (p?<?0.01), but not for 18F-ML-10. Tumour uptake of 18F-ICMT-11 was higher than that of 18F-ML-10 after death-switch induction. PET imaging studies showed that 18F-ICMT-11 can be used to detect apoptosis after death-switch induction, which was accompanied by significantly increased expression of cleaved caspase-3. 18F-FDG signal decreased in tumours after death-switch induction. CONCLUSIONS: We demonstrate that 18F-ICMT-11 can be used to detect caspase-3 activation in a death-switch tumour model, independent of the confounding effects of cancer therapeutics, thus confirming its specificity and supporting the development of this radiotracer for clinical use to monitor tumour apoptosis and therapy response.Citation
Vassileva V, Stribbling S, Barnes C, Carroll L, Braga M, Abrahams J, et al. Evaluation of apoptosis imaging biomarkers in a genetic model of cell death. EJNMMI Res. 2019 Feb 19;9(1):18.Journal
EJNMMI ResearchDOI
10.1186/s13550-019-0487-8PubMed ID
30783791Additional Links
https://dx.doi.org/10.1186/s13550-019-0487-8Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1186/s13550-019-0487-8
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