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Updated: Jun 24, 2026

Studying Cell Death Initiation Using a Digital Microscope
Published on: November 10, 2023
Molecular imaging of cell death
Marijke De Saint-Hubert1, Kristof Prinsen, Luc Mortelmans
1Department of Nuclear Medicine, University Hospital Gasthuisberg Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Abstract:
Apoptosis (programmed cell death) and necrosis (uncontrolled cell death) are two distinct processes of cell death that have been described. Non-invasive molecular imaging of these two processes can have several clinical applications and has various approaches in pre-clinical research. Apoptosis imaging enables a specific and early measurement of response in cancer patients. In case of acute myocardial infarction (AMI) and cerebral stroke the degree of both apoptosis and necrosis is abundant. Imaging of both types of cell death is crucial for diagnosis and could differentiate between "real" and "rescuable" cell damage. In a pre-clinical setting cell death imaging offers the possibility for dynamic study protocols and repeated measurements of cell death in the same animal. This review provides an overview of the radiopharmaceutical development and in vivo evaluation of apoptosis and necrosis detecting radioligands that have emerged so far. Some apoptosis radiopharmaceuticals have made it to clinical trials ((99m)Tc-labeled Anx and (18)F-ML-10) while others need further optimization and evaluation (e.g., (18)F-WC-II-89). (99m)Tc-glucarate has been widely used in patients to image necrosis, but this radiopharmaceutical only works early after the onset of necrosis. Other necrosis avid probes like (123)I labeled hypericin and its monocarboxylic acid derivative and (99m)Tc(CO)(3)-bis-hydrazide-bis-DTPA pamoic acid need further evaluation but show already promising results for imaging of necrosis. As a general conclusion molecular imaging of both apoptosis and necrosis is necessary to understand the cell death process in several pathologies.
Insights
Molecular imaging of apoptosis (programmed cell death) and necrosis (uncontrolled cell death) aids in diagnosing diseases like cancer and stroke. This review covers radiopharmaceuticals for imaging these cell death types in pre-clinical and clinical settings.
Area of Science:
- Biomedical imaging
- Radiopharmaceutical science
- Cell biology
Background:
- Apoptosis and necrosis are distinct cell death processes with clinical implications.
- Non-invasive molecular imaging of cell death offers diagnostic and therapeutic monitoring applications.
- Current pre-clinical research explores various imaging approaches for cell death.
Purpose of the Study:
- To review radiopharmaceutical development for apoptosis and necrosis imaging.
- To evaluate in vivo performance of emerging radioligands.
- To highlight clinical applications and future directions in cell death imaging.
Main Methods:
- Review of published literature on apoptosis and necrosis imaging agents.
- Analysis of radiopharmaceutical development and pre-clinical/clinical evaluation.
- Categorization of imaging agents based on cell death type and stage of development.
Main Results:
- Several apoptosis imaging agents ((99m)Tc-Anx, (18)F-ML-10) have reached clinical trials.
- (99m)Tc-glucarate is used for early necrosis imaging, with other agents showing promise.
- Radioligands like (18)F-WC-II-89 require further optimization.
Conclusions:
- Molecular imaging of both apoptosis and necrosis is essential for understanding various pathologies.
- Continued radiopharmaceutical development is needed for accurate cell death assessment.
- Imaging cell death aids in early diagnosis and treatment response monitoring.

