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@article{Dubash:2018:10.1007/s00259-018-4098-9,
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 = {http://dx.doi.org/10.1007/s00259-018-4098-9},
volume = {45},
year = {2018}
}

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TY  - JOUR
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  - http://dx.doi.org/10.1007/s00259-018-4098-9
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000450713500007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/71802
VL  - 45
ER  -

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