Radiolabeled Bombesin Analogs

Abstract

The gastrin-releasing peptide receptor (GRPR) is expressed in high numbers in a variety of human tumors, including the frequently occurring prostate and breast cancers, and therefore provides the rationale for directing diagnostic or therapeutic radionuclides on cancer lesions after administration of anti-GRPR peptide analogs. This concept has been initially explored with analogs of the frog 14-peptide bombesin, suitably modified at the N-terminus with a number of radiometal chelates. Radiotracers that were selected for clinical testing revealed inherent problems associated with these GRPR agonists, related to low metabolic stability, unfavorable abdominal accumulation, and adverse effects. A shift toward GRPR antagonists soon followed, with safer analogs becoming available, whereby, metabolic stability and background clearance issues were gradually improved. Clinical testing of three main major antagonist types led to promising outcomes, but at the same time brought to light several limitations of this concept, partly related to the variation of GRPR expression levels across cancer types, stages, previous treatments, and other factors. Currently, these parameters are being rigorously addressed by cell biologists, chemists, nuclear medicine physicians, and other discipline practitioners in a common effort to make available more effective and safe state-of-the-art molecular tools to combat GRPR-positive tumors. In the present review, we present the background, current status, and future perspectives of this endeavor.

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“…As a control experiment, cells were also treated with NGO or NGO-BBN-AF750 at the equivalent DOX@NGO-BBN-AF750 concentration. As shown in Figure 6A , no cytotoxicity was found with the NGO group, while a decrease in the cell viability with the NGO-BBN-AF750 group was likely due to the antagonist BBN targeting onto the cells ( 54 – 56 ). Notably, both free DOX and DOX@NGO-BBN-AF750 groups showed significant decreases in cell viability and a dose-dependent cytotoxicity response on HSC-3 cells.…”

Non-conventional and Investigational PET Radiotracers for Breast Cancer: A Systematic Review

“…Gastrin releasing peptide receptor (GRPR) belongs to subtype II of the bombesin receptor (BBN) family. It is a seven-transmembrane G protein-coupled receptor conjugated with BBN ( 204 ). The main physiological role of gastrin-releasing peptide (GRP) is the release of gastrin, contributing to the regulation of enteric function, but it may also hold a function in carcinogenesis and cell proliferation ( 205 ).…”

Do gluten peptides stimulate weight gain in humans?

“…As discussed above, endogenously secreted satiety and metabolism regulatory peptides all have very short half‐life times (2–6 min; Table 2). For this reason, nonoral routes of peptide delivery, such as infusion and regular injection (Ferreira et al, 2017; Mansi et al, 2021; Pierre et al, 2015) are required to maintain sufficient concentrations and bioactivity. To overcome this, the pharmaceutical industry has worked intensively on strategies for producing molecularly modified peptides, which have a lower susceptibility to degradation (Adessi & Soto, 2002; Muheem et al, 2016).…”

“…As discussed above, endogenously secreted satiety and metabolism regulatory peptides all have very short half-life times (2-6 min; Table 2). For this reason, nonoral routes of peptide delivery, such as infusion and regular injection (Ferreira et al, 2017;Mansi et al, 2021;Pierre et al, 2015) are required F I G U R E 3 No relation between per capita wheat consumption and obesity estimations based on data from OMS, USDA, OCDE and Canimot. With permission modified from (Braun, 2016) to maintain sufficient concentrations and bioactivity.…”