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

Autor: Marianna Inglese, Eric O. Aboagye, Kasia Kozlowski, Francesco Mauri, Andrew Thornton, R C Coombes, Laura M. Kenny, Shairoz Merchant, N Masrour, N Rama, Susan Cleator, Adrian Lim, Kathrin Heinzmann, Conrad R. Lewanski, J F Steel, Ioannis Lavdas, Suraiya Dubash
Přispěvatelé: Cancer Research UK
Rok vydání: 2018
Předmět:
Male
Indoles
Lung Neoplasms
Necrosis
medicine.medical_treatment
Apoptosis
[18F]ICMT-11
030218 nuclear medicine & medical imaging
0302 clinical medicine
PET TRACER
Image Processing
Computer-Assisted
Caspase 7
[F-18]ICMT-11
medicine.diagnostic_test
Caspase 3
Radiology
Nuclear Medicine & Medical Imaging
General Medicine
Middle Aged
INDUCED TUMOR APOPTOSIS
3. Good health
Gene Expression Regulation
Neoplastic
Nuclear Medicine & Medical Imaging
Caspase-3
ANNEXIN-V SCINTIGRAPHY
Positron emission tomography
030220 oncology & carcinogenesis
Isatin sulfonamide
Female
medicine.symptom
Life Sciences & Biomedicine
MRI
Adult
Azides
Programmed cell death
Biodistribution
0299 Other Physical Sciences
Breast Neoplasms
IMAGING AGENT
03 medical and health sciences
Breast cancer
medicine
Humans
Radiology
Nuclear Medicine and imaging
Lung cancer
Aged
Chemotherapy
Science & Technology
business.industry
1103 Clinical Sciences
IN-VITRO
medicine.disease
EVOLUTION
F-18-ML-10
Enzyme Activation
CELL-DEATH
Positron-Emission Tomography
CIRCULATING BIOMARKERS
Cancer research
business
Zdroj: European Journal of Nuclear Medicine and Molecular Imaging. 45:2285-2299
ISSN: 1619-7089
1619-7070
DOI: 10.1007/s00259-018-4098-9
Popis: 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.
Databáze: OpenAIRE
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