Imperial College London


Faculty of MedicineDepartment of Surgery & Cancer




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BibTex format

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 = {},
volume = {9},
year = {2019}

RIS format (EndNote, RefMan)

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 -
UR -
VL - 9
ER -