Altmetric

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

Title: Clinical translation of [F-18]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer
Authors: Dubash, SR
Merchant, S
Heinzmann, K
Mauri, F
Lavdas, I
Inglese, M
Kozlowski, K
Rama, N
Masrour, N
Steel, JF
Thornton, A
Lim, AK
Lewanski, C
Cleator, S
Coombes, RC
Kenny, L
Aboagye, EO
Item Type: Journal Article
Abstract: Background 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. Results 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. Conclusion 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.
Issue Date: 1-Dec-2018
Date of Acceptance: 17-Jul-2018
URI: http://hdl.handle.net/10044/1/71802
DOI: https://dx.doi.org/10.1007/s00259-018-4098-9
ISSN: 1619-7070
Publisher: Springer Verlag
Start Page: 2285
End Page: 2299
Journal / Book Title: European Journal of Nuclear Medicine and Molecular Imaging
Volume: 45
Issue: 13
Copyright Statement: © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: C2536/A16584
Keywords: Science & Technology
Life Sciences & Biomedicine
Radiology, Nuclear Medicine & Medical Imaging
Apoptosis
Positron emission tomography
[F-18]ICMT-11
Isatin sulfonamide
Caspase-3
ANNEXIN-V SCINTIGRAPHY
INDUCED TUMOR APOPTOSIS
CELL-DEATH
CIRCULATING BIOMARKERS
IMAGING AGENT
PET TRACER
IN-VITRO
EVOLUTION
MRI
F-18-ML-10
Apoptosis
Caspase-3
Isatin sulfonamide
Positron emission tomography
[18F]ICMT-11
Adult
Aged
Azides
Breast Neoplasms
Caspase 3
Caspase 7
Enzyme Activation
Female
Gene Expression Regulation, Neoplastic
Humans
Image Processing, Computer-Assisted
Indoles
Lung Neoplasms
Male
Middle Aged
Positron-Emission Tomography
Humans
Breast Neoplasms
Lung Neoplasms
Azides
Indoles
Positron-Emission Tomography
Gene Expression Regulation, Neoplastic
Enzyme Activation
Image Processing, Computer-Assisted
Adult
Aged
Middle Aged
Female
Male
Caspase 3
Caspase 7
Science & Technology
Life Sciences & Biomedicine
Radiology, Nuclear Medicine & Medical Imaging
Apoptosis
Positron emission tomography
[F-18]ICMT-11
Isatin sulfonamide
Caspase-3
ANNEXIN-V SCINTIGRAPHY
INDUCED TUMOR APOPTOSIS
CELL-DEATH
CIRCULATING BIOMARKERS
IMAGING AGENT
PET TRACER
IN-VITRO
EVOLUTION
MRI
F-18-ML-10
Nuclear Medicine & Medical Imaging
1103 Clinical Sciences
0299 Other Physical Sciences
Publication Status: Published
Online Publication Date: 2018-09-27
Appears in Collections:Division of Surgery
Division of Cancer



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons