TY - JOUR
T1 - Radiolabeled bombesin analogs
AU - Mansi, Rosalba
AU - Nock, Berthold A.
AU - Dalm, Simone U.
AU - Busstra, Martijn B.
AU - van Weerden, Wytske M.
AU - Maina, Theodosia
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.This article belongs to the Special Issue Radiopharmaceuticals for Oncological Diseases
AB - 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.This article belongs to the Special Issue Radiopharmaceuticals for Oncological Diseases
UR - http://www.scopus.com/inward/record.url?scp=85119061758&partnerID=8YFLogxK
U2 - 10.3390/cancers13225766
DO - 10.3390/cancers13225766
M3 - Review article
AN - SCOPUS:85119061758
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 22
M1 - 5766
ER -
