PET Diagnostic Molecules Utilizing Multimeric Cyclic RGD Peptide Analogs for Imaging Integrin αvβ3 Receptors

被引：41
作者：
Liolios, Christos [1 ,2 ]
Sachpekidis, Christos [3 ]
Kolocouris, Antonios [2 ]
Dimitrakopoulou-Strauss, Antonia [3 ]
Bouziotis, Penelope [1 ]
机构：
[1] Natl Ctr Sci Res Demokritos, Inst Nucl & Radiol Sci & Technol Energy & Safety, Radiochem Studies Lab, Athens 15310, Greece
[2] Natl & Kapodistrian Univ Athens, Dept Pharm, Sect Pharmaceut Chem, Lab Med Chem, Athens 15771, Greece
[3] German Canc Res Ctr, Clin Cooperat Unit Nucl Med, D-69120 Heidelberg, Germany
来源：
MOLECULES | 2021年 / 26卷 / 06期
关键词：
PET imaging; multimeric radioligands; integrin α (v)β (3); cyclic RGD; CANCER ALPHA(V)-INTEGRIN EXPRESSION; POSITRON-EMISSION-TOMOGRAPHY; F-18-ALFATIDE II; BIOLOGICAL EVALUATION; LUNG-CANCER; MICROPET; ANGIOGENESIS; RADIOHALOGENATION; PHARMACOKINETICS; OPTIMIZATION;
D O I：
10.3390/molecules26061792
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Multimeric ligands consisting of multiple pharmacophores connected to a single backbone have been widely investigated for diagnostic and therapeutic applications. In this review, we summarize recent developments regarding multimeric radioligands targeting integrin alpha(v)beta(3) receptors on cancer cells for molecular imaging and diagnostic applications using positron emission tomography (PET). Integrin alpha(v)beta(3) receptors are glycoproteins expressed on the cell surface, which have a significant role in tumor angiogenesis. They act as receptors for several extracellular matrix proteins exposing the tripeptide sequence arginine-glycine-aspartic (RGD). Cyclic RDG peptidic ligands c(RGD) have been developed for integrin alpha(v)beta(3) tumor-targeting positron emission tomography (PET) diagnosis. Several c(RGD) pharmacophores, connected with the linker and conjugated to a chelator or precursor for radiolabeling with different PET radionuclides (F-18, Cu-64, and Ga-68), have resulted in multimeric ligands superior to c(RGD) monomers. The binding avidity, pharmacodynamic, and PET imaging properties of these multimeric c(RGD) radioligands, in relation to their structural characteristics are analyzed and discussed. Furthermore, specific examples from preclinical studies and clinical investigations are included.
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页数：27
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