RESUMEN
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 188Re-cetuximab for imaging and treatment of EGFR-positive cancer. MATERIALS AND METHODS: 188Re-cetuximab was prepared by adding 0.37-0.74 GBq/0.5 ml of 188Re-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: 188Re-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 188Re-cetuximab was increased dose-dependently. NanoSPECT/CT imaging revealed that 188Re-cetuximab could continually target the tumor region for at least 48 h. CONCLUSION: The highly specific targeted property of 188Re-cetuximab suggested that it is suitable as a diagnostic tool and maybe a potent radioimmunotherapy agent in EGFR-positive cancers.
Asunto(s)
Cetuximab/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Radioisótopos/administración & dosificación , Renio/administración & dosificación , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cetuximab/química , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Ratones , Radioinmunoterapia , Radioisótopos/química , Renio/química , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Two-dimensional dip-pen nanolithography (DPN) combined with laser-assisted heating is studied using molecular dynamics (MDs) simulations. The effects of humidity, deposition temperature, heating rate (laser-assisted patterning), and cooling rate on ink molecules are evaluated in terms of molecular transference, alkanethiol meniscus characteristics, surface binding energy, number of transferred chains, pattern characteristics, and the diffusion coefficient of ink molecules. The simulation results clearly show that the number of molecules transferred significantly increases with increasing humidity, which leads to increases in meniscus size and pattern size. The surface binding energy decreases and the diffusion coefficient of ink molecules increases with increasing humidity and deposition temperature. The dwell stage has the largest number of molecules transferred and the largest diffusion distance of ink molecules. The number of vaporous water molecules increases when the temperature is above 300 K, which limits meniscus growth and leads to unstable deposition. The DPN transfer efficiency can be significantly enhanced by increasing the laser pulse energy/heating rate. The transfer efficiency improves as the system humidity increases to saturation (374 water molecules).
RESUMEN
BACKGROUND: The value of baseline positron emission tomography (PET) for predicting overall survival (OS) or disease-free survival (DFS) is unclear in patients with nondistant metastatic (locoregional only) esophageal carcinoma. The authors tested the hypothesis that, in this setting, the number of PET abnormalities (NPA) would correlate with OS and DFS. METHODS: The authors of the current study analyzed patients with localized esophageal carcinoma (Stages II and III) who had a baseline PET and endoscopic ultrasonography (EUS) and were all treated with chemoradiotherapy followed by surgery. The standardized uptake value (SUV) of PET avid lesions were evaluated for: SUV of the primary, NPA, peak SUV, and total SUV. Correlations were performed with baseline EUS results, OS, DFS, and clinical and pathologic response. RESULTS: Forty-seven patients who underwent chemoradiotherapy followed by surgery were analyzed. Most patients had clinical Stage III cancer. NPA was significantly associated with OS (Cox model, P = 0.02; log-rank test, P = 0.04) and DFS (P = 0.04). Patients with NPA > 1 had a death hazard ratio of 4.49 (reference, NPA = 1). In a multivariate analysis, NPA was independently predictive of OS (P = 0.03). Alternatively, SUV of the primary tumor, peak SUV, total SUV, and EUS clinical stage did not correlate with the type of response, OS or DFS. CONCLUSIONS: Data from the current study suggest that for nondistant metastatic esophageal carcinoma, baseline PET can predict patient outcome. Baseline NPA (> 1), reflecting the regional nodal metastases, is an independent predictor of OS. Baseline PET may become a useful stratification factor in randomized trials and for individualizing therapy.