Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

European Journal of Nuclear Medicine - Tập 45 - Trang 2285-2299 - 2018
S. R. Dubash1, S. Merchant1, K. Heinzmann1, F. Mauri2, I. Lavdas1, M. Inglese1,3, K. Kozlowski1, N. Rama1, N. Masrour1, J. F. Steel1, A. Thornton1, A. K. Lim2, C. Lewanski4, S. Cleator4, R. C. Coombes4, Laura Kenny1,4, Eric O. Aboagye1
1Department of Surgery and Cancer, Imperial College London Hammersmith Hospital, London, UK
2Department of Radiology, Imperial College Healthcare NHS Trust, London, UK
3Department of Computer, Control and Management Engineering Antonio Ruberti, University of Rome, La Sapienza, Italy
4Department of Oncology, Imperial College Healthcare NHS Trust, London, UK

Tóm tắt

Effective 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. Breast 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. This 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.

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European Journal of Nuclear Medicine

Tập 45

2285-2299

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