# Small Molecule GPCR Ligands for Oncologic Imaging

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2021 · $236,250

## Abstract

Abstract
 G protein-coupled receptors (GPCRs) are the largest family of cell surface receptor proteins in mammalian
cells. In humans, they are encoded by over 800 individual genes and are widely expressed in human tissues,
where they control a wide range of physiological processes. They play a prominent role in neurotransmission,
but also have been shown to be overexpressed in a variety of cancers. While small organic molecule based
positron-emission tomography (PET) imaging agents have been developed for imaging GPCRs involved in
neurotransmission, GPCRs that are expressed on cancer cells have been targeted with radioactively labeled
hormone peptides. In this regard, somatostatin receptors (SSTRs), gastrin-releasing peptide receptors
(GPCRs), neurotensin receptors (NTSRs), and vasoactive intestinal peptide receptors (VPACs) have been
targeted in a variety of cancer types with different radiolabeled peptides. These peptide based agents have had
some success for both imaging and therapy of tumors (particularly the SSTR peptides), however, the
development of small molecule analogs may have advantages over peptides since they can be suitably designed
to modulate potency, selectivity, lipophilicity, and cell permeability to possibly avoid poor tissue penetration, poor
serum stability, and quick elimination. This would be the first study to evaluate a small molecule PET agent for
imaging GPCRs expressed on tumors. We propose to target GRPR as a model system. In recent years, our
group and others have focused on the development of bombesin (BN) peptide analogs radiolabeled with
positron-emitting radionuclides for positron-emission tomographic (PET) imaging of GRPR-positive tumors in
preclinical mouse models. Some of these peptide analogs have been evaluated in human trials with the most
prominent being 68Ga-RM2. A survey of the existing small molecule compounds which act against GRPR has
identified the antagonist, PD176252, as a potential starting point for developing radiolabeled analogs that bind
to GRPR in the context of prostate and breast cancer. The scientific premise is that these small molecule analogs
will have different properties in terms of cell uptake and dissociation kinetics as compared to peptide tracers and
thus may be superior as imaging agents.

## Key facts

- **NIH application ID:** 10150831
- **Project number:** 5R21EB028302-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Buck E. Rogers
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,250
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150831

## Citation

> US National Institutes of Health, RePORTER application 10150831, Small Molecule GPCR Ligands for Oncologic Imaging (5R21EB028302-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10150831. Licensed CC0.

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