[99mTc]Epidermal growth factor receptor–specific nanobody

摘要: A neoplastic tumor is the result of an altered expression proteins that regulate survival and proliferation a cell. The molecular changes associated with development tumors such as changed (up- or downregulation) certain receptors metabolic regulatory components in cell are often used for identification, diagnosis, treatment cancers other pathological conditions. usually detected monoclonal antibodies (mAbs) developed against specific targets, early detection cancer may suitable favorable outcome patient. To this end, mAbs be labeled radionuclides noninvasive vivo target tissue to diagnose condition; techniques positron emission tomography single-photon computed (SPECT) known sensitive enough follow binding image these radiolabeled (1, 2). However, use has limitations because molecules relatively large do not penetrate solid tumors; addition they stay blood circulation long time tend accumulate liver (3, 4). Investigators constantly searching evaluating alternatives conventional have similar applications, but superior production stability characteristics.One alternative antibody variable fragment (Fv), genetically engineered by linking variable-heavy (VH) -light (VL) chain antibody, which also involved antigen binding, through flexible peptide linker obtain single-chain Fv (scFv) (5). scFv its linkers susceptible enzymatic digestion under conditions, show reduced affinity toward target, aggregate easily (6). Another unique class immunoglobulins found Camelidae species (camels llamas) consists only heavy component traditional mAb. These contain single domain interacts (7). smallest, functional, antigen-binding fragments can produced from immunoglobin, domains VHH nanobody. Nanobodies more stable than inexpensively variety systems yeast, filamentous fungi, even plants (8-10). Also, nanobodies aggregation compared fragments, been shown low immunogenicity mice repeated administration animals did evoke anti-nanobody response (11).The epidermal growth factor receptor (EGFR) characteristic overexpression those breast, ovaries, lungs, head neck, bladder, colon (12). EGFR 170-kDa transmembrane protein promotes on autocrine (EGF) transforming α (TGFα), operates receptor-associated tyrosine kinase–mediated signal transduction pathway. progression some attributed either both organ increased level activation EGF TGFα constitutive kinase pathway caused mutated kinase. In effort develop therapy activity kinase, inhibitors evaluated compete (e.g., receptor) small inhibit signaling (13). 350 clinical trials approved United States Food Drug Administration. Roovers et al. (14) generated anti-EGFR were meta-stable technetium (99mTc), Huang investigate imaging (15) Gainkam study biodistribution (16) bearing xenograft tumors.