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Molecular imaging of apoptosis: from micro to macro.

Zeng W, Wang X, Xu P, Liu G, Eden HS, Chen X - Theranostics (2015)

Bottom Line: Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies.In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features.Their clinical translation will also be our focus.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Pharmaceutical Sciences, and Molecular Imaging Research Centre, Central South University, Changsha, 410013, China;

ABSTRACT
Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus.

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Related in: MedlinePlus

Representative radiolabeling strategies: (A) macrocyclic chelators, (B) Tc chelating agents and (C) 18F synthons.
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Figure 1: Representative radiolabeling strategies: (A) macrocyclic chelators, (B) Tc chelating agents and (C) 18F synthons.

Mentions: Radionuclide Labeling Strategies. There are various radiolabeling strategies available to incorporate a radionuclide into a probe molecule (Figure 1). The choice of technique for a radiochemist depends primarily on the radionuclide used 40. For instance, since many metallic radionuclides possess the ability to form stable complexes with chelating agents, radioactive metals are often labeled via complexation with a chelator, thus allowing further conjugation with probe molecules. Metal isotopes, including 64Cu, 68Ga and 111In are introduced to the tracers mainly with the aid of certain polyaminopolycarboxylic ligands, such as 1,4,7,10-tetraaza-cyclodecane-1,4,7,10-tetraacetic acid (DOTA), 2,2',2''-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) and diethylene triamine pentaacetic acid (DTPA). These chelators are efficient in coordinating the metals with all of the amino groups and some of the carboxyls. The multiple bonding sites lead to high binding strengths. Metals such as 99mTc can be efficiently chelated by other chelating groups. Although bare 99mTc can complex with polydentate chelators, such as boronic acid adducts or DTPA, the more favorable forms are [Tc=O]3+ or Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC), which possess better stability. Various chelators with a combinational form of NxS4-x have proved effective in binding with [Tc=O]3+, resulting in a square pyramidal structure with Tc in the center 41. 18F has so far been the most utilized radioisotope in PET imaging. Compared to the radiometal-labeling method, where the labeling process is no more than an instantaneous coordination, the 18F fluorination is far more complicated. There are generally two forms of 18F precursors, [18F]F (such as K[18F]F and Cs[18F]F) and [18F]F2 or its derivative (such as acetyl hypofluorite (CH3COO[18F]F)). Although there are reports of using these two precursors for direct peptide labeling, generally these approaches are regarded as inefficient and lacking chemoselectivity, and are rarely employed. Practically, it is more common to convert the 18F precursors to certain forms of 18F-labeled prosthetic groups (called synthons) and to use those synthons for peptide labeling. Due to the specificity of probe molecules for targets, attaching a bulky radiolabeled chelating group or a prosthetic group may influence the biological activity of the probe molecules. Therefore, site-specific radiochemistry is needed and important for the preparation of biologically active probes 42.


Molecular imaging of apoptosis: from micro to macro.

Zeng W, Wang X, Xu P, Liu G, Eden HS, Chen X - Theranostics (2015)

Representative radiolabeling strategies: (A) macrocyclic chelators, (B) Tc chelating agents and (C) 18F synthons.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4377726&req=5

Figure 1: Representative radiolabeling strategies: (A) macrocyclic chelators, (B) Tc chelating agents and (C) 18F synthons.
Mentions: Radionuclide Labeling Strategies. There are various radiolabeling strategies available to incorporate a radionuclide into a probe molecule (Figure 1). The choice of technique for a radiochemist depends primarily on the radionuclide used 40. For instance, since many metallic radionuclides possess the ability to form stable complexes with chelating agents, radioactive metals are often labeled via complexation with a chelator, thus allowing further conjugation with probe molecules. Metal isotopes, including 64Cu, 68Ga and 111In are introduced to the tracers mainly with the aid of certain polyaminopolycarboxylic ligands, such as 1,4,7,10-tetraaza-cyclodecane-1,4,7,10-tetraacetic acid (DOTA), 2,2',2''-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) and diethylene triamine pentaacetic acid (DTPA). These chelators are efficient in coordinating the metals with all of the amino groups and some of the carboxyls. The multiple bonding sites lead to high binding strengths. Metals such as 99mTc can be efficiently chelated by other chelating groups. Although bare 99mTc can complex with polydentate chelators, such as boronic acid adducts or DTPA, the more favorable forms are [Tc=O]3+ or Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC), which possess better stability. Various chelators with a combinational form of NxS4-x have proved effective in binding with [Tc=O]3+, resulting in a square pyramidal structure with Tc in the center 41. 18F has so far been the most utilized radioisotope in PET imaging. Compared to the radiometal-labeling method, where the labeling process is no more than an instantaneous coordination, the 18F fluorination is far more complicated. There are generally two forms of 18F precursors, [18F]F (such as K[18F]F and Cs[18F]F) and [18F]F2 or its derivative (such as acetyl hypofluorite (CH3COO[18F]F)). Although there are reports of using these two precursors for direct peptide labeling, generally these approaches are regarded as inefficient and lacking chemoselectivity, and are rarely employed. Practically, it is more common to convert the 18F precursors to certain forms of 18F-labeled prosthetic groups (called synthons) and to use those synthons for peptide labeling. Due to the specificity of probe molecules for targets, attaching a bulky radiolabeled chelating group or a prosthetic group may influence the biological activity of the probe molecules. Therefore, site-specific radiochemistry is needed and important for the preparation of biologically active probes 42.

Bottom Line: Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies.In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features.Their clinical translation will also be our focus.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Pharmaceutical Sciences, and Molecular Imaging Research Centre, Central South University, Changsha, 410013, China;

ABSTRACT
Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus.

Show MeSH
Related in: MedlinePlus