Production of large quantities of 90 Y by ion-exchange chromatography using an organic resin and a chelating agent Abmel Xiques Castillo a, ⁎ , Marylaine Pérez-Malo a , Keila Isaac-Olivé a , Heyam Mukhallalati b,1 , Edgar Casanova González a , Mirta Torres Berdeguez a , Néstor Cornejo Díaz c a Centro de Isótopos (CENTIS), Ave. Monumental y Carretera La Rada Km 3 1/2, Guanabacoa, Havana, Cuba b Division of Radiopharmaceuticals, Atomic Energy Commission of Syria, Damascus, Syria c Centro de Protección e Higiene de las Radiaciones, AP: 6195 Habana 6, CP 10600, Havana, Cuba Received 25 September 2009; received in revised form 5 February 2010; accepted 30 March 2010 Abstract The performance of a system composed of an organic cation exchanger (Dowex 50Wx8) and a chelating agent (EDTA) previously described for the successful production of 90 Y via a 90 Sr/ 90 Y generator is assessed under dynamic conditions. In an attempt to overcome the established limitation of ion-exchange resins for the separation of subcurie quantities of activity, 90 Y is repeatedly isolated from an 11.8-GBq (320 mCi) 90 Sr cow using a three-column tandem arrangement. The high recovery and radionuclidic purity obtained for 90 Y and the parameters of the separation (time, eluant concentration, pH and flow rate range) strongly suggest that Ci quantities of 90 Y can be handled satisfactorily by the ion-exchange method. No replacement or treatment of the cow, low waste generation and 90 Sr losses less than 0.1% after each run were observed during the present study which, in combination with the low cost of this resin, may result in an attractive alternate method for the production of large quantities of 90 Y. © 2010 Elsevier Inc. All rights reserved. Keywords: 90 Sr/ 90 Y generator; Ion-exchange separation; 90 Y production; 90 Y for targeted therapy 1. Introduction 90 Y has long been used for therapy, with its main applications being in radiosynovectomy [1], treatment of liver carcinoma [2] and radioimmunotherapy [3–5]. Al- though it can be produced by the neutron irradiation of 89 Y in oxide form, this is expensive and the 90 Y product contains large amounts of inactive 89 Y, making it unsuitable for the preparation of labeled antibodies and peptides used for targeted therapy [7]. This last application has spurred its demand due to the encouraging results with the 90 Y-based radiopharmaceutical Zevalin and its approval for the treatment of non-Hodgkin's lymphoma by the Food and Drug Administration [6]. Very high specific activity 90 Y (near theoretical maximum) is produced from the decay of 90 Sr, which is an abundant fission product of 235 U found in nuclear wastes resulting from the reprocessing of spent commercial nuclear fuel and in the separation of 239 Pu for weapons manufacture [7]. The 28-year half-life of 90 Sr makes the 90 Sr– 90 Y pair ideal for the construction of a radioisotope generator from which 90 Y can be produced in an almost inexhaustible manner. Many methods like ion exchange [8–14], precipitation [15], different extraction techniques [16,17] and electrodeposition [18] have been reported for the separation of 90 Y from 90 Sr. However, only a few of them have proved to be amenable regarding generator construction [18]. Ion-exchange methods using an organic resin and a chelator/complexor are simple and fast, but unlike 99 Mo/ 99m Tc and 188 W/ 188 Re generators they do not provide a ready-to-use eluate. Usually, the eluting agent should be removed prior to labeling to avoid the need for post-labeling purification. The major disadvantage, never- theless, is the limited resistance of organic support materials to radiolysis which limits the amount of activity that can Available online at www.sciencedirect.com Nuclear Medicine and Biology 37 (2010) 935 – 942 www.elsevier.com/locate/nucmedbio ⁎ Corresponding author. E-mail address: axcastillo@yahoo.com (A.X. Castillo). 1 Contributed partially to this work during her training as an IAEA fellow related to SYR/2/004 project. 0969-8051/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.nucmedbio.2010.03.017