RESUMEN
Nitroimidazole derivatives are of current interest in the development of hypoxia targeting agents and show potential in the establishment of quantitative measures of tumor hypoxia. In this study, the binding of 2-nitroimidazole to albumin was probed using NMR diffusion and relaxation measurements. Binding studies were conducted at three different protein concentrations (0.23, 0.30 and 0.38mM) with drug concentrations ranging from 0.005-0.16M at 298K. Quantitative assessments of the binding model were made by evaluating the number of binding sites, n, and association constant, K. These were determined to be 21±3 and 53±4M-1, respectively.
Asunto(s)
Espectroscopía de Resonancia Magnética/métodos , Nitroimidazoles/metabolismo , Albúmina Sérica Humana/metabolismo , Difusión , Humanos , Nitroimidazoles/química , Albúmina Sérica Humana/químicaRESUMEN
OBJECTIVE: To evaluate the serial changes and correlations between readout-segmented technique with navigated phase correction diffusion-weighted MRI (DWI), R2*-MRI and (18)F-FDG positron emission tomography (PET) CT performed before and during radiation therapy (RT) in patients with mucosal primary head and neck cancer. METHODS: The mean apparent diffusion coefficient (ADCmean) from DWI (at b = 50 and 800 s mm(-2)), the mean R2* values derived from T2(*)-MRI, and PET metabolic parameters, including maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) were measured for the primary tumour. Spearman correlation coefficients were calculated to evaluate correlations between ADCmean, R2*, SUVmax, MTV and TLG. A paired t-test was performed to assess the MRI changes and the slope of serial MRI changes during RT. RESULTS: Pre-treatment scans were performed in 28 patients and mid-treatment scans in 20 patients. No significant correlation was found between ADCmean and either R2* values or PET parameters. There were significant negative correlations of R2* values with pre-treatment PET parameters but not with mid-RT PET parameters: pre-SUVmax (p = 0.008), pre-MTV (p = 0.006) and pre-TLG (p = 0.008). A significant rise in ADCmean was found during the first half (p < 0.001) of RT but not in the second half (p = 0.215) of the treatment. There was an increase of the ADCmean values of 279.4 [95% confidence interval (95% CI): 210-348] in the first half of the treatment (Weeks 0-3). However, during the second-half period of treatment, the mean ADC value (Weeks 3-6) was 24.0 and the 95% CI (-40 to 88) included zero. This suggests that there was no significant change in ADC values during the second half of the treatment. CONCLUSION: A significant negative correlation was found between pre-treatment R2*-MRI and PET parameters. DWI appeared to demonstrate potentially predictable changes during RT. ADVANCES IN KNOWLEDGE: Understanding the correlation and changes that occur with time between potential imaging biomarkers may help us establish the most appropriate biomarkers to consider in future research.