GRPr Theranostics: Current Status of Imaging and Therapy using GRPr Targeting Radiopharmaceuticals

Abstract

Addressing molecular targets, that are overexpressed by various tumor entities, using radiolabeled molecules for a combined diagnostic and therapeutic (theranostic) approach is of increasing interest in oncology. The gastrin-releasing peptide receptor (GRPr), which is part of the bombesin family, has shown to be overexpressed in a variety of tumors, therefore, serving as a promising target for those theranostic applications. A large amount of differently radiolabeled bombesin derivatives addressing the GRPr have been evaluated in the preclinical as well as clinical setting showing fast blood clearance and urinary excretion with selective GRPr-binding. Most of the available studies on GRPr-targeted imaging and therapy have evaluated the theranostic approach in prostate and breast cancer applying bombesin derivatives tagged with the predominantly used theranostic pair of ⁶⁸Ga/¹⁷⁷Lu which is the focus of this review.

Zusammenfassung

Die Suche nach molekularen Targets, die bei verschiedenen Tumorarten überexprimiert werden, mit Einsatz radioaktiv markierter Moleküle für einen kombinierten diagnostischen und therapeutischen (theranostischen) Ansatz ist in der Onkologie von zunehmendem Interesse. Es hat sich gezeigt, dass der Rezeptor GRPr („gastrin-releasing peptide receptor“), der zur Familie der Bombesine gehört, in einer Vielzahl von Tumoren überexprimiert wird und daher ein vielversprechendes Ziel für solche theranostischen Anwendungen darstellt. Eine große Zahl unterschiedlich radioaktiv markierter Bombesin-Derivate, die an GRPr binden, wurde sowohl im präklinischen als auch im klinischen Umfeld evaluiert und zeigte eine schnelle Blut-Clearance und Urinausscheidung mit selektiver GRPr-Bindung. Die meisten verfügbaren Studien zur GRPr-basierten Bildgebung und Therapie haben den theranostischen Ansatz bei Prostata- und Brustkrebs untersucht, unter Verwendung von Bombesin-Derivaten, die mit dem vorwiegend eingesetzten theranostischen Paar ⁶⁸Ga/¹⁷⁷Lu markiert sind, das im Mittelpunkt dieser Übersicht steht.

Schlüsselwörter

Theranostika - Gastrin-releasing peptid receptor - Bombesin - Prostatakarzinom - Brustkrebs - Gallium-68/ Lutetium-177

Keywords

Theranostics - gastrin-releasing peptide receptor - bombesin - prostate cancer - breast cancer - Gallium-68/ Lutetium-177

Publication History

Received: 29 October 2021

Accepted: 22 January 2022

Article published online:
03 June 2022

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