Background/Aim: Cetuximab has exhibited high EGFR-targeting specificity and clinical promise in previous studies. In this study, we formulated unit dose kits for preparation of high specific activity 188 Re-cetuximab for imaging and treatment of EGFR-positive cancer. Materials and Methods: 188 Re-cetuximab was prepared by adding 0.37-0.74 GBq/0.5 ml of 188 Re-perrhenate for 4 h at 37˚C. Cell surface expression of EGFR, cell binding and cytotoxic effects were evaluated in vitro using both EGFR-positive (NCI-H292, A431) and EGFR-negative (BT483) tumors. A nanoSPECT/CT imaging study was performed in mice bearing EGFR-expressing NCI-H292 tumors. Results: 188 Re-cetuximab bound specifically to EGFR-expressing cells and labeling of radionuclides to cetuximab preserved the binding ability of the antibody. Besides, the cytotoxic effect of 188 Re-cetuximab was increased dosedependently. NanoSPECT/CT imaging revealed that 188 Recetuximab could continually target the tumor region for at least 48 h. Conclusion: The highly specific targeted property of 188 Re-cetuximab suggested that it is suitable as a diagnostic tool and maybe a potent radioimmunotherapy agent in EGFRpositive cancers. Advantages include non-invasive screening and visualization of specific membranous target expression in multiple lesions simultaneously. These whole-body scans can be performed repetitively and enable detection of changes in target expression in response to treatment. Therefore, PET and SPECT are very useful in treatment strategies that combine therapeutics with diagnostics, also known as "theranostics." Epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER-1) expressed on normal human cells has been associated with the control of cell survival, proliferation, and metabolism (7, 8). Higher levels of expression of the receptor have also been shown to be correlated with malignancy in a variety of cancers including colorectal, lung, breast, and head and neck (9-12). Abnormal EGFR activity initiates and promotes mechanisms responsible for tumor growth and progression, including cell proliferation and maturation, angiogenesis, invasion, metastasis, and inhibition of apoptosis. In addition, studies showed that overexpression of EGFR by 183
Clinical studies have demonstrated that the γ-aminobutyric acid type A (GABAA) receptor complex plays a central role in the modulation of anxiety. Conditioned fear and anxiety-like behaviors have many similarities at the neuroanatomical and pharmacological levels. The radioactive GABA/BZR receptor antagonist, fluorine-18-labeled flumazenil, [18F]flumazenil, behaves as a potential PET imaging agent for the evaluation of cortical damage of the brain in stroke, alcoholism, and for Alzheimer disease investigation. The main goal of our study was to investigate a fully automated nucleophilic fluorination system, with solid extraction purification, developed to replace traditional preparation methods, and to detect underlying expressions of contextual fear and characterize the distribution of GABAA receptors in fear-conditioned rats by [18F]flumazenil. A carrier-free nucleophilic fluorination method using an automatic synthesizer with direct labeling of a nitro-flumazenil precursor was implemented. The semi-preparative high-performance liquid chromatography (HPLC) purification method (RCY = 15–20%) was applied to obtain high purity [18F]flumazenil. Nano-positron emission tomography (NanoPET)/computed tomography (CT) imaging and ex vivo autoradiography were used to analyze the fear conditioning of rats trained with 1–10 tone-foot-shock pairings. The anxiety rats had a significantly lower cerebral accumulation (in the amygdala, prefrontal cortex, cortex, and hippocampus) of fear conditioning. Our rat autoradiography results also supported the findings of PET imaging. Key findings were obtained by developing straightforward labeling and purification procedures that can be easily adapted to commercially available modules for the high radiochemical purity of [18F]flumazenil. The use of an automatic synthesizer with semi-preparative HPLC purification would be a suitable reference method for new drug studies of GABAA/BZR receptors in the future.
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