Gastrin-releasing peptide receptor agonists and antagonists for molecular imaging of breast and prostate cancer: from pre-clinical studies to translational perspectives

ABSTRACT

Introduction

Prostate and breast cancer represent a leading cause of cancer-related death worldwide with a dramatic social and demographic impact. Gastrin-releasing peptide receptors (GRPRs), part of the bombesin (BBN) family, have been found overexpressed in both the aforementioned malignancies, and have emerged as a potentially useful target to combine imaging and therapy in a unique, synergistic approach, namely ‘theranostics.’

Areas Covered

The biological characteristics of GRPRs, as well as their aberrant expression in breast and prostate cancer, are covered. Furthermore, the role of the different available GRPR agonists and antagonists, labeled with radionuclides suitable for molecular imaging through single photon computed tomography (SPECT) or positron emission computed (PET/CT), is reviewed, with a particular focus on the potential theranostic implications.

Expert opinion

GRPR-targeted molecular imaging of breast and prostate cancer gave promising results in pre-clinical studies. Notably, GRPRs’ expression was found to be inversely correlated with disease progression in both prostate and breast cancer. Among the different GRPR agonists and antagonists applied as imaging probes, RM26 presented particularly interesting applications, with meaningful theranostic potential, but its diagnostic performance resulted highly influenced by the choice of the chelator-radionuclide complex, being long-life radionuclides more suitable for obtaining high-contrast imaging.

KEYWORDS:

• Breast cancer
• molecular imaging
• PET/CT
• prostate cancer
• SPECT/CT
• theranostics

Article highlights

• Gastrin-releasing peptide receptors (GRPR) represent an emerging hallmark of breast and prostate cancer.

• Density of GRPR expression in prostate and breast cancer resulted inversely correlated with disease biological aggressiveness and progression.

• Several GRPR-ligands (both agonists and antagonists) have been synthesized and labeled with radionuclides suitable for imaging or therapy, according to the so-called ‘theranostic approach’

• GRPR-antagonists have shown more favorable properties than agonists, since they do not activate GRPR-pathway, thus preventing unwanted gastro-intestinal side-effects.

• Pre-clinical and preliminary clinical studies have provided encouraging results for GRPR-targeted molecular imaging of breast and prostate cancer.

• GRPR-targeted molecular imaging with positron emission tomography (PET) technology has found limited application due to the shortage of long-life positron emitting radionuclides suitable for late acquisition, needed due to GRPR-antagonists slow clearance from blood pool.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The authors have no funding to report.