New neurotensin analogue radiolabeled by 99m‐technetium as a potential agent for tumor identification

Emrarian, Iman; Sadeghzadeh, Nourollah; Abedi, Seyed Mohammad; Abediankenari, Saeid

doi:10.1111/cbdd.13082

Cited by 8 publications

(3 citation statements)

References 34 publications

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“…Interestingly, it has been recently questioned whether neurotensin receptor (NTR), namely NTR1, could be the new SSTR [44]. Indeed, this receptor has been successfully targeted in vivo using radiolabeled molecules for diagnostic imaging and radionuclide therapy of NTR1-expressing tumors [45,46,47,48,49,50].…”

Section: Introductionmentioning

confidence: 99%

Less Exploited GPCRs in Precision Medicine: Targets for Molecular Imaging and Theranostics

et al. 2018

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Precision medicine relies on individually tailored therapeutic intervention taking into account individual variability. It is strongly dependent on the availability of target-specific drugs and/or imaging agents that recognize molecular targets and patient-specific disease mechanisms. The most sensitive molecular imaging modalities, Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET), rely on the interaction between an imaging radioprobe and a target. Moreover, the use of target-specific molecular tools for both diagnostics and therapy, theranostic agents, represent an established methodology in nuclear medicine that is assuming an increasingly important role in precision medicine. The design of innovative imaging and/or theranostic agents is key for further accomplishments in the field. G-protein-coupled receptors (GPCRs), apart from being highly relevant drug targets, have also been largely exploited as molecular targets for non-invasive imaging and/or systemic radiotherapy of various diseases. Herein, we will discuss recent efforts towards the development of innovative imaging and/or theranostic agents targeting selected emergent GPCRs, namely the Frizzled receptor (FZD), Ghrelin receptor (GHSR-1a), G protein-coupled estrogen receptor (GPER), and Sphingosine-1-phosphate receptor (S1PR). The pharmacological and clinical relevance will be highlighted, giving particular attention to the studies on the synthesis and characterization of targeted molecular imaging agents, biological evaluation, and potential clinical applications in oncology and non-oncology diseases. Whenever relevant, supporting computational studies will be also discussed.

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Section: Introductionmentioning

confidence: 99%

Less Exploited GPCRs in Precision Medicine: Targets for Molecular Imaging and Theranostics

et al. 2018

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“…Thus, NTS and NTSR1 are promising candidates for digestive cancers clinical screening and targeting. Recently, some studies conducted on PDAC 67,69,[109][110][111] and CRC 112,113 have developed radiopharmaceuticals targeting NTSR1 for diagnostic and therapeutic application. Radiolabeled peptide and nonpeptide tracers have been designed which are promising PET imaging probes for diagnosis, allowing the discrimination between patients with PDAC and those who only suffer from pancreas inflammation.…”

Section: Discussion and Remarksmentioning

confidence: 99%

Neurotensin pathway in digestive cancers and clinical applications: an overview

et al. 2020

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Initially, NEUROTENSIN (NTS) has been shown to play physiological and biological functions as a neuro-transmitter/modulator in the central nervous system and as an endocrine factor in the periphery, through its binding to two kinds of receptors: NTSR1 and 2 (G protein-coupled receptors) and NTSR3/sortilin (a vacuolar protein-sorting 10-domain receptor). NTS also plays oncogenic roles in many types of cancer, including digestive cancers. In tumor tissues, NTS and NTSR1 expression is higher than in healthy ones and is associated with poor prognosis. NTS and NTRS1 promote cancer progression and play key functions in metastatic processes; they modulate several signaling pathways and they contribute to changes in the tumor microenvironment. Conversely, NTRS2 involvement in digestive cancers is poorly understood. Discovered for mediating NTS biological effects, sortilin recently emerged as a promising target as its expression was found to be increased in various types of cancers. Because it can be secreted, a soluble form of sortilin (sSortilin) appears as a new serum biomarker which, on the basis of recent studies, promises to be useful in both the diagnosis and tumor progression monitoring. More precisely, it appears that soluble sortilin can be associated with other receptors like TRKB. These associations occur in exosomes and trigger the aggressiveness of cancers like glioblastoma, leading to the concept of a possible composite theranostic biomarker. This review summarizes the oncogenic roles of the NTS signaling pathways in digestive cancers and discusses their emergence as promising early diagnostic and/or prognostic biomarkers and therapeutic targets.

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“…Hydrazino nicotinic acid (HYNIC) is an extremely effective and well‐established bifunctional chelator that allows biomolecules to be readily radiolabeled with 99m Tc efficiently using a variety of coligand systems among which EDDA/tricine has shown favorable pharmacokinetics and targeting affinity (Emrarian, Sadeghzadeh, Abedi, & Abediankenari, 2018).…”

Section: Introductionmentioning

confidence: 99%

Preparation and evaluation of ^99mTc‐HYNIC‐_D(TPPE) as a new targeted imaging probe for detection of colon cancer: Preclinical comparison with ^99mTc‐HYNIC‐EPPT

et al. 2020

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The aim of this study was to prepare radiolabeled peptide‐based agents for imaging of colon cancer. According to the incorporation of HYNIC for radiolabeling with technetium‐99m, two analogs were designed and compared: an antitumor‐antibody‐derived peptide based on the EPPT sequence and a novel retro‐inverso peptidomimetic derivative D(TPPE) structurally modified by replacing the L‐amino acids with D‐amino acids and reversing the primary amino acid sequence of EPPT. The HYNIC‐conjugated peptides were labeled with 99mTc using tricine/EDDA coligand with more than 98% radiochemical yield and showed high metabolic stability. Kd values of 41.77 ± 7.34 nM and 37.33 ± 8.37 nM for 99mTc‐HYNIC‐EPPT and 99mTc‐HYNIC‐D(TPPE) confirmed high affinity of both peptides for cell surface antigen MUC1. These radiotracers demonstrated no significant differences in the cellular uptake and internalization value, but the biodistribution profile of 99mTc‐HYNIC‐D(TPPE) was more favorable than that of 99mTc‐HYNIC‐EPPT as a result of better tumor‐to‐non‐target ratios for the examined tissues and organs. HT29 tumors were visualized more clearly in scintigraphic images with 99mTc‐HYNIC‐D(TPPE) in comparison with 99mTc‐HYNIC‐EPPT. The results showed the retro‐inverso analog to be a more promising radiotracer as a probe for in vivo targeting of HT‐29 tumors than the parent peptide.

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New neurotensin analogue radiolabeled by 99m‐technetium as a potential agent for tumor identification

Cited by 8 publications

References 34 publications

Less Exploited GPCRs in Precision Medicine: Targets for Molecular Imaging and Theranostics

Less Exploited GPCRs in Precision Medicine: Targets for Molecular Imaging and Theranostics

Neurotensin pathway in digestive cancers and clinical applications: an overview

Preparation and evaluation of ^99mTc‐HYNIC‐_D(TPPE) as a new targeted imaging probe for detection of colon cancer: Preclinical comparison with ^99mTc‐HYNIC‐EPPT

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New neurotensin analogue radiolabeled by 99m‐technetium as a potential agent for tumor identification

Cited by 8 publications

References 34 publications

Less Exploited GPCRs in Precision Medicine: Targets for Molecular Imaging and Theranostics

Less Exploited GPCRs in Precision Medicine: Targets for Molecular Imaging and Theranostics

Neurotensin pathway in digestive cancers and clinical applications: an overview

Preparation and evaluation of 99mTc‐HYNIC‐D(TPPE) as a new targeted imaging probe for detection of colon cancer: Preclinical comparison with 99mTc‐HYNIC‐EPPT

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Preparation and evaluation of ^99mTc‐HYNIC‐_D(TPPE) as a new targeted imaging probe for detection of colon cancer: Preclinical comparison with ^99mTc‐HYNIC‐EPPT