Imperial College London


Faculty of MedicineDepartment of Surgery & Cancer




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BibTex format

author = {Dubash, SR and Merchant, S and Heinzmann, K and Mauri, F and Lavdas, I and Inglese, M and Kozlowski, K and Rama, N and Masrour, N and Steel, JF and Thornton, A and Lim, AK and Lewanski, C and Cleator, S and Coombes, RC and Kenny, L and Aboagye, EO},
doi = {10.1007/s00259-018-4098-9},
journal = {European Journal of Nuclear Medicine and Molecular Imaging},
pages = {2285--2299},
title = {Clinical translation of [F-18]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer},
url = {},
volume = {45},
year = {2018}

RIS format (EndNote, RefMan)

AB - BackgroundEffective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy.ResultsBreast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes.ConclusionThis study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer.
AU - Dubash,SR
AU - Merchant,S
AU - Heinzmann,K
AU - Mauri,F
AU - Lavdas,I
AU - Inglese,M
AU - Kozlowski,K
AU - Rama,N
AU - Masrour,N
AU - Steel,JF
AU - Thornton,A
AU - Lim,AK
AU - Lewanski,C
AU - Cleator,S
AU - Coombes,RC
AU - Kenny,L
AU - Aboagye,EO
DO - 10.1007/s00259-018-4098-9
EP - 2299
PY - 2018///
SN - 1619-7070
SP - 2285
TI - Clinical translation of [F-18]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer
T2 - European Journal of Nuclear Medicine and Molecular Imaging
UR -
UR -
UR -
VL - 45
ER -