Design, preparation and biological evaluation of a 177Lu-labeled somatostatin receptor antagonist for targeted therapy of neuroendocrine tumors

Behnammanesh, Hossein; Jokar, Safura; Erfani, Mostafa; Geramifar, Parham; Sabzevari, Omid; Amini, Mohsen; Mazidi, Seyed Mohammad; Hajiramezanali, Maliheh; Beiki, Davood

doi:10.1016/j.bioorg.2019.103381

Cited by 8 publications

(7 citation statements)

References 41 publications

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“…The detection of SSTR2 amplification in 30% of our sequenced MPNSTs, which is supported by FISH and RNA sequencing but not immunoreactivity, is novel and of clinical interest, because somatostatin receptor antagonists are available in clinical practice [ 28 ]. However, the biological impact of SSTR2 is unclear; with evidence in the literature supporting both a pro‐tumour survival signal and cancer growth inhibition [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours

Lyskjær

Lindsay

Tirabosco

et al. 2020

The Journal of Pathology

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Diagnosing MPNST can be challenging, but genetic alterations recently identified in polycomb repressive complex 2 (PRC2) core component genes, EED and SUZ12, resulting in global loss of the histone 3 lysine 27 trimethylation (H3K27me3) epigenetic mark, represent drivers of malignancy and a valuable diagnostic tool. However, the reported loss of H3K27me3 expression ranges from 35% to 84%. We show that advances in molecular pathology now allow many MPNST mimics to be classified confidently. We confirm that MPNSTs harbouring mutations in PRC2 core components are associated with loss of H3K27me3 expression; whole‐genome doubling was detected in 68%, and SSTR2 was amplified in 32% of MPNSTs. We demonstrate that loss of H3K27me3 expression occurs overall in 38% of MPNSTs, but is lost in 76% of histologically classical cases, whereas loss was detected in only 23% cases with heterologous elements and 14% where the diagnosis could not be provided on morphology alone. H3K27me3 loss is rarely seen in other high‐grade sarcomas and was not found to be associated with an inferior outcome in MPNST. We show that DNA methylation profiling distinguishes MPNST from its histological mimics, was unrelated to anatomical site, and formed two main clusters, MeGroups 4 and 5. MeGroup 4 represents classical MPNSTs lacking H3K27me3 expression in the majority of cases, whereas MeGroup 5 comprises MPNSTs exhibiting non‐classical histology and expressing H3K27me3 and cluster with undifferentiated sarcomas. The two MeGroups are distinguished by differentially methylated PRC2‐associated genes, the majority of which are hypermethylated in the promoter regions in MeGroup 4, indicating that the PRC2 target genes are not expressed in these tumours. The methylation profiles of MPNSTs with retention of H3K27me3 in MeGroups 4 and 5 are independent of mutations in PRC2 core components and the driver(s) in these groups remain to be identified. Our results open new avenues of investigation. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 99%

H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours

Lyskjær

Lindsay

Tirabosco

et al. 2020

The Journal of Pathology

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“…Somatostatin receptor 2 (SSTR2) was the object of efforts to develop new ligands for treating neuroendocrine tumors (NETs). This receptor is the target of the previously mentioned somatostatin analogs DOTA-TOC and DOTA-TATE, but the focus of attention has recently shifted to developing receptor antagonists because they can bind to a larger number of sites, leading to a higher tumor uptake [ 33 ]. With this in mind, Behnammanesh and coworkers [ 33 ] developed a series of SSTR2 antagonists and labeled them with 177 Lu by means of the DOTA chelator.…”

Section: Resultsmentioning

confidence: 99%

“…This receptor is the target of the previously mentioned somatostatin analogs DOTA-TOC and DOTA-TATE, but the focus of attention has recently shifted to developing receptor antagonists because they can bind to a larger number of sites, leading to a higher tumor uptake [ 33 ]. With this in mind, Behnammanesh and coworkers [ 33 ] developed a series of SSTR2 antagonists and labeled them with 177 Lu by means of the DOTA chelator. Docking analysis then helped the authors to identify the peptide with the most successful accommodation at the binding site of the receptor (the DOTA-peptide 2, DOTA-p-Cl-Phe-Cyclo( d -Cys- l -BzThi- d -Aph-Lys-Thr-Cys)- d -Tyr-NH 2 ).…”

Section: Resultsmentioning

confidence: 99%

Radionuclide Delivery Strategies in Tumor Treatment: A Systematic Review

Poletto

Cecchin²,

Bartoletti³

et al. 2022

CIMB

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The aim of this review was to assess recent progress in targeted radionuclide tumor therapy, focusing on the best delivery strategies. A literature search was conducted in PubMed, Web of Science, and Scopus using the terms “radionuclides”, “liposomes”, “avidin–biotin interaction”, “theranostic”, and “molecular docking”. The 10 year filter was applied, except for the avidin–biotin interaction. Data were retrieved from both preclinical and clinical settings. Three targeting strategies were considered: pretargeting, liposomes, and ligands. Pretargeting can be achieved by exploiting the avidin–biotin interaction. This strategy seems very promising, although it has been investigated mainly in resectable tumors. Radiolabeled liposomes have attracted new interest as probes to identify the most suitable patients for treatment with liposomal formulations of common chemotherapeutics. The use of ligands for the delivery of radiotherapeutics to a specific target is still the most appealing strategy for treating tumors. The most appropriate ligand can be identified by virtually simulating its interaction with the receptor. All strategies showed great potential for use in targeted radionuclide therapy, but they also have numerous drawbacks. The most promising option is probably the one based on the use of new ligands.

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“…SPECT/CT imaging clearly showed that the activity is localized in tumors. The favorable antagonistic properties of 177Lu‐DOTA‐Peptide 2 on the SSTRs can make it a suitable candidate for peptide receptor radionuclide therapy (PRRT) (Behnammanesh et al, 2020).…”

Section: Common Surface Receptors As Anti‐cancer Drug Targetsmentioning

confidence: 99%

“…Similarly, the development of a new SSTR peptide ligand labeled with 177Lu was created to achieve a therapeutic targeted tumor treatment by Behnammanesh et al, (2020). It showed the docked interactions of selected and drowned ligands in the active site of…”

Section: Somatostatin Receptorsmentioning

confidence: 99%

Surface receptor‐mediated targeted drug delivery systems for enhanced cancer treatment: A state‐of‐the‐art review

Kunjiappan

Pavadai

Sivakumar

et al. 2020

Drug Development Research

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Enhanced cancer treatment remains as one of the focused areas for researchers around the world. Hence, the progress in this direction will be a challenge and an opportunity in, inter‐disciplinary field to mitigate the suffering of millions in the upcoming decades. As we see, cancer death rate has also progressively increased despite the current impressive treatment regimens but also due to the non‐availability of vaccines and the re‐occurring of cancer in substantially recovered patients. Currently, numerous treatment strategies like surgical removal of solid tumors followed by radiation with a combination of immunotherapy/chemotherapy by the researchers and clinicians are routinely being followed. However, recurrence and distant metastasis often occur following radiation therapy, commonly due to the generation of radio‐resistance through deregulation of the cell cycle, cell death, and inhibition of DNA damage repair mechanisms. Thus, chemotherapeutic/immunotherapeutic treatment systems have progressed remarkably in the latest years owing to destroying tumors, noninvasive, and affordable charge of therapy. But, traditional chemotherapeutic approaches target the DNA of mutated and normal healthy cells, resulting in a significantly increased risk of toxicity and drug resistance. Thus, many receptors targeted therapies are in the developmental phase of discovery. Cancer cells have a specialized set of surface receptors that provide potential targets for cancer therapeutics. Cell surface receptor‐dependent endocytosis is well a known major mechanism for the internalization of macromolecular drugs. This review emphasizes the recent development of several surface receptors mediated cancer‐targeting approaches for the effective delivery of various therapeutic formulations.

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Design, preparation and biological evaluation of a 177Lu-labeled somatostatin receptor antagonist for targeted therapy of neuroendocrine tumors

Cited by 8 publications

References 41 publications

H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours

H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours

Radionuclide Delivery Strategies in Tumor Treatment: A Systematic Review

Surface receptor‐mediated targeted drug delivery systems for enhanced cancer treatment: A state‐of‐the‐art review

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