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

João Franco Machado,Rita Melo,Rúben D Silva,João D G Correia

doi:10.3390/molecules24010049

João Franco Machado, Rita Melo + Show 2 more

Open Access

https://doi.org/10.3390/molecules24010049

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Abstract

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.

Highlights

Precision medicine, sometimes named personalized medicine, is a fast-growing approach for disease treatment, which, in general terms, aims at delivering an “appropriate dose of a right drug to a right patient” [1,2,3,4]
We have surveyed recent efforts towards the design and introduction of innovative molecular clinical relevance of such efforts. Among these G-protein-coupled receptors (GPCRs), the Ghrelintheranostic receptor (GHSR)-1a is undoubtedly the one that has imaging and/or theranostic agents targeting the Frizzled receptor (FZD), G protein-Coupled Estrogen Receptor (GPER), GHSR-1a, and Sphingosine-1-phosphate receptor (S1PR), highlighting the been most exploited, and various radiolabeled tracers, namely those derived from human ghrelin, clinical relevance of such efforts
Among these GPCRs, the GHSR-1a is undoubtedly the one that has were developed for noninvasive imaging of GHSR-1a at the preclinical level

Summary

Introduction

Sometimes named personalized medicine, is a fast-growing approach for disease treatment, which, in general terms, aims at delivering an “appropriate dose of a right drug to a right patient” [1,2,3,4]. These results validated the use of radiolabeled FZD10 -specific antibodies for cancer theranostics Another important study case of an anti-FZD10 therapeutic approach is the humanized chimeric antibody OTSA-101 (2) developed by Giraudet et al (Figure 1). Competition assays by pretreatment with the high potent and selective GSHR-1a inhibitor YIL781 (Ki = 17 nM), demonstrated that [11C]-19 was an highly selective ligand for GSHR-1a in pancreas, which prompted the authors to claim its usefulness as a PET radiotracer for in vivo imaging of GHSR-1a in that organ [198].

Growth

GPER-targeting

Sphingosine

18 F-based

Findings

Concluding