Leung Kam
National for Biotechnology Information, NLM, NIH, Bethesda, MD
Epidermal growth factor (EGF) is a 53-amino acid cytokine (6.2 kDa) that is secreted by ectodermic cells, monocytes, kidneys, and duodenal glands (1). EGF stimulates growth of epidermal and epithelial cells. EGF and at least seven other growth factors and their transmembrane receptor kinases play important roles in cell proliferation, survival, adhesion, migration, and differentiation. The EGF receptor (EGFR) family consists of four transmembrane receptors, including EGFR (HER1/erbB-1), HER2 (erbB-2/neu), HER3 (erbB-3), and HER4 (erbB-4) (2). HER1, HER3, and HER4 comprise three major functional domains: an extracellular ligand-binding domain, a hydrophobic transmembrane domain, and a cytoplasmic tyrosine kinase domain. No ligand has been clearly identified for HER2; however, HER2 can be activated as a result of ligand binding to other HER receptors with the formation of receptor homodimers and/or heterodimers (3). HER1 as well as HER2 are overexpressed on many solid tumor cells such as breast, non–small-cell lung, head and neck, and colon cancers (4-6). The high levels of HER1 and HER2 expression on cancer cells are associated with a poor prognosis (7-10). Trastuzumab, a humanized immunoglobulin G (IgG) monoclonal antibody against the extracellular domain of recombinant HER2 (11), was labeled as In-trastuzumab (12-14). C225, an anti-EGFR (HER1), mouse-human chimeric, monoclonal IgG antibody, also known as erbitux and cetuximab, was labeled as Tc-EC-C225 (15, 16) for imaging EGFR expression on solid tumors using single-photon emission computed tomography (SPECT). For evaluation as a positron emission tomography (PET) imaging agent for EGFR, Y has been attached to cetuximab CHX-A''-diethylenetriamine pentaacetic acid (CHX-A''-DTPA) to form Y-CHX-A''-DTPA-cetuximab (17).
表皮生长因子（EGF）是一种由外胚层细胞、单核细胞、肾脏和十二指肠腺分泌的含53个氨基酸的细胞因子（6.2 kDa）（1）。EGF刺激表皮细胞和上皮细胞的生长。EGF以及至少其他七种生长因子及其跨膜受体激酶在细胞增殖、存活、黏附、迁移和分化中发挥重要作用。表皮生长因子受体（EGFR）家族由四种跨膜受体组成，包括EGFR（HER1/erbB-1）、HER2（erbB-2/neu）、HER3（erbB-3）和HER4（erbB-4）（2）。HER1、HER3和HER4包含三个主要功能结构域：细胞外配体结合结构域、疏水跨膜结构域和细胞质酪氨酸激酶结构域。尚未明确鉴定出HER2的配体；然而，HER2可因配体与其他HER受体结合形成受体同二聚体和/或异二聚体而被激活（3）。HER1和HER2在许多实体瘤细胞如乳腺癌、非小细胞肺癌、头颈癌和结肠癌中均有过表达（4-6）。癌细胞上HER1和HER2的高表达与预后不良相关（7-10）。曲妥珠单抗是一种针对重组HER2细胞外结构域的人源化免疫球蛋白G（IgG）单克隆抗体（11），曾被标记为In-曲妥珠单抗（12-14）。C225是一种抗EGFR（HER1）的鼠-人嵌合单克隆IgG抗体，也称为爱必妥和西妥昔单抗，被标记为Tc-EC-C225（15,16），用于通过单光子发射计算机断层扫描（SPECT）对实体瘤上的EGFR表达进行成像。为了评估作为EGFR的正电子发射断层扫描（PET）成像剂，已将Y连接到西妥昔单抗的环己二胺四乙酸（CHX-A''-DTPA）上，形成Y-CHX-A''-DTPA-西妥昔单抗（17）。
