Leung Kam
National for Biotechnology Information, NLM, NIH, Bethesda, MD
Epidermal growth factor (EGF) is a 53-amino-acid cytokine (6.2 kDa) 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, mouse-human chimeric, monoclonal IgG antibody, also known as cetuximab) was labeled as Tc-EC-C225 (15, 16) for single-photon emission computed tomography (SPECT) imaging of EGFR expression on solid tumors. However, positron emission tomography (PET) offers better sensitivity, resolution, and quantification than SPECT (17). Cu ( = 12.7 h, β decay) is an attractive radionuclide for labeling cetuximab. Panitimumab has been approved by the United States Food and Drug Administration as a single agent for the treatment of EGFR-expressing, metastatic colorectal carcinoma. For evaluation as a PET imaging agent, Cu was attached to panitumumab 1,4,7,10-tetraazacyclododecane-,','','''-tetraacetic acid (DOTA) to form Cu-DOTA-panitumumab. Niu et al. (18) performed PET imaging studies in nude mice bearing human head and neck squamous cell carcinoma (HNSCC) tumors with different expressions of EGFR and found an unexpected inverse relationship with radioactivity accumulation and EGFR density in the tumors.
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。EGF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以及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（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）被标记为In - 曲妥珠单抗（12 - 14）。C225（一种抗EGFR的鼠 - 人嵌合单克隆IgG抗体，也称为西妥昔单抗）被标记为Tc - EC - C225（15, 16）用于实体瘤上EGFR表达的单光子发射计算机断层扫描（SPECT）成像。然而，正电子发射断层扫描（PET）比SPECT具有更好的灵敏度、分辨率和定量能力（17）。铜（ = 12.7小时，β衰变）是用于标记西妥昔单抗的一种有吸引力的放射性核素。帕尼单抗已被美国食品药品监督管理局批准作为单一药物用于治疗表达EGFR的转移性结直肠癌。为了评估作为PET成像剂，将铜连接到帕尼单抗的1,4,7,10 - 四氮杂环十二烷 - 四乙酸（DOTA）上以形成Cu - DOTA - 帕尼单抗。牛等人（18）在携带不同EGFR表达的人头颈部鳞状细胞癌（HNSCC）肿瘤的裸鼠中进行了PET成像研究，发现肿瘤中的放射性积累与EGFR密度之间存在意外的反比关系。
