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@article{Vassileva:2019:10.1186/s13550-019-0487-8,
author = {Vassileva, V and Stribbling, S and Barnes, C and Carroll, L and Braga, V and Abrahams, J and Heinzmann, K and Haegeman, C and MacFarlane, M and Simpson, K and Dive, C and Honeychurch, J and Illidge, T and Aboagye, E},
doi = {10.1186/s13550-019-0487-8},
journal = {EJNMMI Research},
title = {Evaluation of apoptosis imaging biomarkers in a genetic model of cell death},
url = {http://dx.doi.org/10.1186/s13550-019-0487-8},
volume = {9},
year = {2019}
}

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TY  - JOUR
AB  - PurposeWe 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.MethodsCaspase-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.ResultsSignificantly 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.ConclusionsWe 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 r
AU  - Vassileva,V
AU  - Stribbling,S
AU  - Barnes,C
AU  - Carroll,L
AU  - Braga,V
AU  - Abrahams,J
AU  - Heinzmann,K
AU  - Haegeman,C
AU  - MacFarlane,M
AU  - Simpson,K
AU  - Dive,C
AU  - Honeychurch,J
AU  - Illidge,T
AU  - Aboagye,E
DO  - 10.1186/s13550-019-0487-8
PY  - 2019///
SN  - 2191-219X
TI  - Evaluation of apoptosis imaging biomarkers in a genetic model of cell death
T2  - EJNMMI Research
UR  - http://dx.doi.org/10.1186/s13550-019-0487-8
UR  - http://hdl.handle.net/10044/1/67330
VL  - 9
ER  -

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