The Significance of NK1 Receptor Ligands and Their Application in Targeted Radionuclide Tumour Therapy.

Ewa Gniazdowska,Paweł Krzysztof Halik,Agnieszka Majkowska-Pilip

doi:10.3390/pharmaceutics11090443

Ewa Gniazdowska, Paweł Krzysztof Halik + Show 1 more

Open Access

https://doi.org/10.3390/pharmaceutics11090443

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Journal: Pharmaceutics	Publication Date: Sep 1, 2019
Citations: 34	License type: CC BY 4.0

Affiliation: Instytut Chemii i Techniki Jądrowej

Abstract

To date, our understanding of the Substance P (SP) and neurokinin 1 receptor (NK1R) system shows intricate relations between human physiology and disease occurrence or progression. Within the oncological field, overexpression of NK1R and this SP/NK1R system have been implicated in cancer cell progression and poor overall prognosis. This review focuses on providing an update on the current state of knowledge around the wide spectrum of NK1R ligands and applications of radioligands as radiopharmaceuticals. In this review, data concerning both the chemical and biological aspects of peptide and nonpeptide ligands as agonists or antagonists in classical and nuclear medicine, are presented and discussed. However, the research presented here is primarily focused on NK1R nonpeptide antagonistic ligands and the potential application of SP/NK1R system in targeted radionuclide tumour therapy.

Highlights

Neurokinin 1 receptor (NK1R), known as tachykinin receptor 1 (TACR1), belongs to the tachykinin receptor subfamily of G protein-coupled receptors (GPCRs), called seven-transmembrane domain receptors (Figure 1) [1,2,3]
Tachykinins, widely distributed within the central (CNS) and peripheral (PNS) nervous system, are small bioactive neuropeptides which share a conserved C-terminal pentapeptide sequence, Phe-X-Gly-Leu-Met-NH2. Examples of these neurotransmitters belonging to the tachykinin group include Substance P (SP), the first neuropeptide discovered in mammals [5], neurokinin A (NKA) and neurokinin B (NKB)
Therapeutic radiopharmaceuticals used in cancer treatment or palliative therapy are often ligands labelled with radionuclides which emit corpuscular radiation of short range in the tissue (e.g., β−, α or Auger electrons)

Summary

Introduction

Neurokinin 1 receptor (NK1R), known as tachykinin receptor 1 (TACR1), belongs to the tachykinin receptor subfamily of G protein-coupled receptors (GPCRs), called seven-transmembrane domain receptors (Figure 1) [1,2,3]. Tachykinins, widely distributed within the central (CNS) and peripheral (PNS) nervous system, are small bioactive neuropeptides which share a conserved C-terminal pentapeptide sequence, Phe-X-Gly-Leu-Met-NH2. Examples of these neurotransmitters belonging to the tachykinin group include Substance P (SP), the first neuropeptide discovered in mammals [5], neurokinin A (NKA) and neurokinin B (NKB). These compounds listed above are the preferential ligands for NK1, NK2 and NK3 receptors, respectively, they can bind additional NK receptors with varying affinity [6]. Mvoolvreeotvheer,ubsaesoefdroandihoilgahbedlelendsiNtyKo1fRtralingsamndems ibnrtaanregNeteKd1Rrasdoinonhuucmliadne ctuanmcoeur rcethllesr,anpeyw[2th,1e5r–a1p7e]u. tic approaches involve the use of radiolabelled NK1R ligands in targeted radioTnhueclaidime tuofmtohuisr rtheverieawpyis[2t,1o5d–1is7c]u. ss data from recent literature concerning the chemical and bioloTghicealaiamspoecfttshoisf nreavtuierwal iasntdosdyinstchuestsicdNatKa 1fRrolmigarnecdesnitnlictlearsastiucrael acnodncneurncilneagrtmheedchiceimnei,cawlitahnda bspioelcoigfiiccafol causspoecntstaorgf entaetduraldiaonnducslyindtehtehteicraNpKy.1R ligands in classical and nuclear medicine, with a specific focus on targeted radionuclide therapy

NK1R Ligands in Classical Medicine

Application of NK1R Antagonists

Radiolabelled NK1R Agonists for Targeted Radionuclide Tumour Therapy

Antagonist Radioligands of NK1R for Targeted Radionuclide Imaging

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