Development of [18F]ICMT-11 for Imaging Caspase-3/7 Activity during Therapy-Induced Apoptosis

Garcia-Arguello, Segundo Francisco; Lopez-Lorenzo, Beatriz; Cornelissen, Bart; Smith, Graham

doi:10.3390/cancers12082191

Cited by 9 publications

(6 citation statements)

References 54 publications

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“…These are small molecules that form a reversible covalent bond in the active site of caspase-3 and -7 with high affinity by nucleophilic attack of the caspase cysteine at the 3-carbonyl group of the isatin moiety, which corresponds to the warhead of the molecule [ 24 , 25 ]. Their nanomolar affinity to caspase-3/7, with IC 50 values ranging from 0.5 to 80 nM for caspase-3 ( Table 1 ), and their low molecular weight made them good probe candidates to image caspase-3/7 activity [ 24 , 26 ]. They are, however, often prone to metabolic degradation.…”

Section: Small Molecule Probesmentioning

confidence: 99%

“…[ 18 F]ICMT-11 was evaluated in many preclinical tumor models, using various cell lines and treatments [ 26 ]. These preclinical studies had varying results but generally showed a 1.5- to 2.5-fold higher uptake of the radiotracer in treated tumors compared to controls.…”

Section: Small Molecule Probesmentioning

confidence: 99%

“…This approach showed a higher regional tumor uptake of the radiotracer in patients who responded to the therapy. It is mentioned that this tracer uptake is not an exclusive marker of response, as reviewed by Garcia-Arguello et al, including an extensive analysis of the preclinical and clinical studies of [ 18 F]ICMT-11 [ 26 ].…”

Section: Small Molecule Probesmentioning

confidence: 99%

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Molecular Imaging of Apoptosis: The Case of Caspase-3 Radiotracers

Beroske

Wyngaert

Stroobants

et al. 2021

IJMS

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The molecular imaging of apoptosis remains an important method for the diagnosis and monitoring of the progression of certain diseases and the evaluation of the efficacy of anticancer apoptosis-inducing therapies. Among the multiple biomarkers involved in apoptosis, activated caspase-3 is an attractive target, as it is the most abundant of the executioner caspases. Nuclear imaging is a good candidate, as it combines a high depth of tissue penetration and high sensitivity, features necessary to detect small changes in levels of apoptosis. However, designing a caspase-3 radiotracer comes with challenges, such as selectivity, cell permeability and transient caspase-3 activation. In this review, we discuss the different caspase-3 radiotracers for the imaging of apoptosis together with the challenges of the translation of various apoptosis-imaging strategies in clinical trials.

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Section: Small Molecule Probesmentioning

confidence: 99%

Section: Small Molecule Probesmentioning

confidence: 99%

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Molecular Imaging of Apoptosis: The Case of Caspase-3 Radiotracers

Beroske

Wyngaert

Stroobants

et al. 2021

IJMS

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“…Caspases belong to the cysteine proteases family and are intricately involved in the apoptotic process. In fact, activating the “executioner” caspase-3 enzyme initiates the breakdown of major structural proteins within the cell [ 19 ]. Based on our results, GA exposure markedly increased Caspase-3/7 activity ( Figure 3a ).…”

Section: Resultsmentioning

confidence: 99%

Gallic Acid Induces S and G2 Phase Arrest and Apoptosis in Human Ovarian Cancer Cells In Vitro

Liu

et al. 2021

Applied Sciences

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Ovarian cancer (OC) is among the top gynecologic cancers in the US with a death tally of 13,940 in the past year alone. Gallic acid (GA) is a natural compound with pharmacological benefits. In this research, the role of GA on cell proliferation, cell apoptosis, cell cycle-related protein expression was explored in OC cell lines OVCAR-3 and A2780/CP70. After 24, 48 and 72 h of GA treatment, the IC50 values in OVCAR-3 cells were 22.14 ± 0.45, 20.36 ± 0.18, 15.13 ± 0.53 μM, respectively and in A2780/CP70 cells IC50 values were 33.53 ± 2.64, 27.18 ± 0.22, 22.81 ± 0.56, respectively. Hoechst 33,342 DNA staining and flow cytometry results showed 20 μM GA exposure could significantly accelerate apoptosis in both OC cell lines and the total apoptotic rate increased from 5.34%(control) to 21.42% in OVCAR-3 cells and from 8.01%(control) to 17.69% in A2780/CP70 cells. Western blot analysis revealed that GA stimulated programmed OC cell death via a p53-dependent intrinsic signaling. In addition, GA arrested cell cycle at the S or G2 phase via p53-p21-Cdc2-cyclin B pathway in the same cells. In conclusion, we provide some evidence of the efficacy of GA in ovarian cancer prevention and therapy.

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“…The half-lives of isotopes used in PET or SPECT tracers are usually short, posing a unique barrier to commonplace application of these modalities for protease imaging. Nevertheless, the technology was successfully demonstrated for imaging metalloproteases [ 263 , 264 , 265 ], cysteine cathepsins [ 266 , 267 , 268 ] and caspases [ 269 , 270 ] in preclinical settings. In CT imaging modalities, X-rays are used to create cross-sectional images with high resolution and this technique is widely used for noninvasive clinical imaging [ 271 ].…”

Section: Monitoring Protease Activity In Cancermentioning

confidence: 99%

The Tumor Proteolytic Landscape: A Challenging Frontier in Cancer Diagnosis and Therapy

Vizovišek¹,

Ristanovic²,

Menghini³

et al. 2021

IJMS

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In recent decades, dysregulation of proteases and atypical proteolysis have become increasingly recognized as important hallmarks of cancer, driving community-wide efforts to explore the proteolytic landscape of oncologic disease. With more than 100 proteases currently associated with different aspects of cancer development and progression, there is a clear impetus to harness their potential in the context of oncology. Advances in the protease field have yielded technologies enabling sensitive protease detection in various settings, paving the way towards diagnostic profiling of disease-related protease activity patterns. Methods including activity-based probes and substrates, antibodies, and various nanosystems that generate reporter signals, i.e., for PET or MRI, after interaction with the target protease have shown potential for clinical translation. Nevertheless, these technologies are costly, not easily multiplexed, and require advanced imaging technologies. While the current clinical applications of protease-responsive technologies in oncologic settings are still limited, emerging technologies and protease sensors are poised to enable comprehensive exploration of the tumor proteolytic landscape as a diagnostic and therapeutic frontier. This review aims to give an overview of the most relevant classes of proteases as indicators for tumor diagnosis, current approaches to detect and monitor their activity in vivo, and associated therapeutic applications.

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Development of [18F]ICMT-11 for Imaging Caspase-3/7 Activity during Therapy-Induced Apoptosis

Cited by 9 publications

References 54 publications

Molecular Imaging of Apoptosis: The Case of Caspase-3 Radiotracers

Molecular Imaging of Apoptosis: The Case of Caspase-3 Radiotracers

Gallic Acid Induces S and G2 Phase Arrest and Apoptosis in Human Ovarian Cancer Cells In Vitro

The Tumor Proteolytic Landscape: A Challenging Frontier in Cancer Diagnosis and Therapy

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