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 (68Ga), Copper-64 (64Cu), Technetium-99m (99mTc), Lutetium-177 (177Lu), Rhenium-188 (188Re) or Bismuth-213 (213Bi). 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.
鉴于血管生成/新生血管在肿瘤发生、进展及转移扩散中具有关键作用，建立靶向血管生成的成像与治疗载体至关重要。氨肽酶N（APN/CD13）作为血管生成过程的核心生物标志物，在活跃的血管内皮细胞及多种肿瘤细胞表面高表达，是癌症诊断与治疗的重要靶点。由于天冬酰胺-甘氨酸-精氨酸（NGR）序列已被证实与APN/CD13共定位，基于NGR肽介导的血管靶向研究日益受到关注。早期临床前实验已证实，标记镓-68（⁶⁸Ga）、铜-64（⁶⁴Cu）、锝-99m（⁹⁹ᵐTc）、镥-177（¹⁷⁷Lu）、铼-188（¹⁸⁸Re）或铋-213（²¹³Bi）等多种正电子发射断层扫描（PET）与单光子发射计算机断层扫描（SPECT）放射性核素的NGR探针具备成像与治疗可行性。为提升单受体靶向肽的肿瘤结合亲和力与滞留时间，研究者已引入含NGR基序的异源二聚体，以识别多受体过表达的恶性肿瘤。通过多种荷瘤实验动物开展的临床前研究，为探索NGR异源双价配体的体内成像特性提供了有效工具。本文系统综述了已报道的NGR异源二聚体临床前研究成果，这些发现对开发诊断与治疗领域中更具靶向特异性的多价化合物具有重要参考价值。
Radiolabeled NGR-Based Heterodimers for Angiogenesis Imaging: A Review of Preclinical Studies
肿瘤(癌症)患者之家