RESUMEN
A key aspect for the applicability of 89Zr-radioimmunoconjugates is inert modification and radiolabeling. The two commercially available bifunctional variants of the siderophore desferrioxamine (DFO), Fe-DFO-N-suc-TFP-ester and p-NCS-Bz-DFO, are most often used for clinical 89Zr-immuno-PET. The use of Fe-DFO-N-suc-TFP-ester is advantageous with regard to higher radiolysis stability and more facile assessment of radiochemical purity as well as chelator-to-mAb ratio. However, not all mAbs withstand the Fe-removal step at relatively low pH (4-4.5) using EDTA, which is needed after conjugation to allow 89Zr labeling. In this study, it was investigated whether hydroxybenzyl ethylenediamine (HBED) or the clinically approved deferiprone (DFP) can serve as an alternative for EDTA to establish a pH-independent mild method for Fe-removal and thereby broaden the applicability of Fe-DFO-N-suc-TFP-ester. Carrier-added [59Fe]Fe-DFO-N-suc-TFP-ester was used for mAb modification to enable direct tracking of the Fe-removal efficiency under various conditions. Whereas incomplete Fe-removal with HBED was observed at pH 5 or higher, Fe-removal with DFP was possible at a broad pH range (4-9). This provides a mild, pH-independent method for Fe-removal, improving the applicability and attractiveness of Fe-DFO-N-suc-TFP-ester for 89Zr-mAb preparation.
Asunto(s)
Deferoxamina , Hierro , Tomografía de Emisión de Positrones , Radioisótopos , Circonio , Circonio/química , Deferoxamina/química , Radioisótopos/química , Hierro/química , Tomografía de Emisión de Positrones/métodos , Piridonas/química , Deferiprona/química , Inmunoconjugados/química , Radiofármacos/química , Anticuerpos Monoclonales/químicaRESUMEN
This paper reports on absolute activity measurements of iron-59 made at the National Metrology Institute of South Africa (NMISA) via 4π(LS)ß-γ coincidence counting. The exercise formed part of an Asia Pacific Metrology Program (APMP) regional key comparison. Source data were analysed by the extrapolation technique for a number of gamma-ray window settings. In addition, a feasibility study was undertaken on a second technique; a non-extrapolation method based on a detection efficiency analysis. The reported activity concentration of the (59)Fe solution was determined with a relative uncertainty of 0.28% (k=1), the uncertainty being due mainly to the rate vs. efficiency fitting process. The result from the non-extrapolation method was lower than that given by extrapolation by 0.33%, within two standard deviations. Possible reasons for the small discrepancy are discussed.