Trencsényi György, Halmos Gábor, Képes Zita
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
Cancers (Basel). 2023 Sep 7;15(18):4459. doi: 10.3390/cancers15184459.
Since angiogenesis/neoangiogenesis has a major role in tumor development, progression and metastatic spread, the establishment of angiogenesis-targeting imaging and therapeutic vectors is of utmost significance. Aminopeptidase N (APN/CD13) is a pivotal biomarker of angiogenic processes abundantly expressed on the cell surface of active vascular endothelial and various neoplastic cells, constituting a valuable target for cancer diagnostics and therapy. Since the asparagine-glycine-arginine (NGR) sequence has been shown to colocalize with APN/CD13, the research interest in NGR-peptide-mediated vascular targeting is steadily growing. Earlier preclinical experiments have already demonstrated the imaging and therapeutic feasibility of NGR-based probes labeled with different positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radionuclides, including Gallium-68 (Ga), Copper-64 (Cu), Technetium-99m (Tc), Lutetium-177 (Lu), Rhenium-188 (Re) or Bismuth-213 (Bi). To improve the tumor binding affinity and the retention time of single-receptor targeting peptides, NGR motifs containing heterodimers have been introduced to identify multi-receptor overexpressing malignancies. Preclinical studies with various tumor-bearing experimental animals provide useful tools for the investigation of the in vivo imaging behavior of NGR-based heterobivalent ligands. Herein, we review the reported preclinical achievements on NGR heterodimers that could be highly relevant for the development of further target-specific multivalent compounds in diagnostic and therapeutic settings.
由于血管生成/新生血管生成在肿瘤发生、发展和转移扩散中起主要作用，因此建立靶向血管生成的成像和治疗载体至关重要。氨肽酶N（APN/CD13）是血管生成过程的关键生物标志物，在活跃的血管内皮细胞和各种肿瘤细胞的细胞表面大量表达，构成癌症诊断和治疗的重要靶点。由于天冬酰胺-甘氨酸-精氨酸（NGR）序列已被证明与APN/CD13共定位，对NGR肽介导的血管靶向的研究兴趣正在稳步增长。早期的临床前实验已经证明了用不同正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）放射性核素标记的基于NGR的探针的成像和治疗可行性，这些放射性核素包括镓-68（Ga）、铜-64（Cu）、锝-99m（Tc）、镥-177（Lu）、铼-188（Re）或铋-213（Bi）。为了提高单受体靶向肽的肿瘤结合亲和力和保留时间，已引入含有异二聚体的NGR基序来识别多受体过表达的恶性肿瘤。对各种荷瘤实验动物进行的临床前研究为研究基于NGR的异二价配体的体内成像行为提供了有用的工具。在此，我们综述了已报道的关于NGR异二聚体的临床前研究成果，这些成果可能与进一步开发诊断和治疗环境中靶向特定靶点的多价化合物高度相关。
