90 Y separation / 90 Sr/ 90 Y chromatographic generator / 90 Y for clinical use / 90 Y purification / Ion exchange chromatography Summary. There is an increasing interest for 90 Y for radionuclide therapy. However, radioimmunotherapy, one of the most important applications for 90 Y, demands a very high purity product. Obtaining a high quality 90 Y is difficult not only because of the complex and time consuming production schemes but also because of the quality control which has challenging tasks like the determination of 90 Sr at very low concentrations. The present paper investigates a reported purification procedure for the removal of stable metal trace contaminants from an 90 Y solution, seeking for its potential use in the elimination of the radioactive contaminant 90 Sr and its fast determination. For this purpose a washing step with HNO 3 acid is introduced to elute 90 Sr, the order of each acid solution is rearranged to reduce the potential contaminants present in acids and the size of the column is reduced to further optimize the procedure. As a result, an improved purification method is obtained, which allows the removal of both trace metal contaminants and 90 Sr from an 90 Y solution and the measurement of 90 Sr/ 90 Y ratios of the order of 10 −7 , which are well below the established pharmacopeia limit of 2 × 10 −5 .
Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.
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