Reactor production and electrochemical purification of 169 Er: A potential step forward for its utilization in in vivo therapeutic applications Rubel Chakravarty, Sudipta Chakraborty, Viju Chirayil, Ashutosh Dash ⁎ Isotope Application and Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India abstract article info Article history: Received 3 September 2013 Received in revised form 12 November 2013 Accepted 27 November 2013 Keywords: 169 Er Radionuclidic impurity 169 Yb Electrochemical separation Radiation synovectomy Bone pain palliation Introduction: The aim of the present study was to develop and demonstrate a viable method for the reactor production of 169 Er with acceptable specific activity using moderate flux reactor and its purification from 169 Yb following electrochemical pathway based on mercury-pool cathode to avail 169 Er in radionuclidically pure form essential for its therapeutic use. Methods: Erbium-169 was produced in reactor by neutron bombardment of isotopically enriched (98.2% in 168 Er) erbium target at a thermal neutron flux of ~8 × 10 13 n.cm -2 .s -1 for 21 d. A thorough optimization of irradiation parameters including neutron flux, irradiation time and target cooling time was carried out. The influence of different experimental parameters for the quantitative removal 169 Yb from 169 Er was investigated, optimized and based on the results; a two-cycle electrochemical separation procedure was adopted. The suitablility of purified 169 Er for application in radiation synovectomy and bone pain palliation was ascertained by carrying out radiolabeling studies with hydroxypaptite (HA) particles and 1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraaminomethylene phosphonic acid (DOTMP), respectively. Results: Thermal neutron irradiation of 10 mg of isotopically enriched (98.2% in 168 Er) erbium target at a flux of ~8 × 10 13 n.cm -2 .s -1 for 21 d followed by a two-step electrochemical separation of 169 Yb impurity yielded ~ 3.7 GBq (100 mCi) of 169 Er with a specific activity of ~ 370 MBq/mg (10 mCi/mg) and radionuclidic purity of N 99.99%. The reliability of this approach was amply demonstrated by performing several production batches, where the performance of each batch remained consistent. The utility of the purified 169 Er was demonstrated in the radiolabeling studies with HA particles and DOTMP, wherein both the radiolabeled products were obtained with high radiolabeling yield (N 99%). Conclusions: A viable strategy for the batch production and purification of 169 Er, suitable for therapeutic applications, has been developed and demonstrated. © 2014 Elsevier Inc. All rights reserved. 1. Introduction Radiation synovectomy (RSV), which involves intraarticular injection of beta-emitting radionuclides in colloidal or particulate form (1–10 μm size range) into the affected synovial joints, has emerged as an effective treatment modality in patients suffering from inflammatory-rheumatoid and degenerative joint diseases [1–7]. In this modality, the radionuclides are taken up by the synovial lining cells, phagocytized by the outermost cellular layer of the synovial membrane and deliver radiation dose to the synovium without ex- cessive irradiation of surrounding tissue. The selection of a beta emitting radionuclide represents the cornerstone for the success of radiosynovectomy and is primarily based on the size of the joint to be treated. As the synovial thickness of different joints in the human body (e.g., finger, wrist, knee, etc.) vary substantially, a wide range of radionuclides with optimum tissue penetration ranges are recom- mended to treat smaller joints (finger), medium joints (wrist, elbow, shoulder and ankle) and large joints (knee) [3,8–12]. There is a great deal of interest in the use of 169 Er (T ½ = 9.4 d) for RSV of digital joints such as, metacarpophalangeal, metatarsophalangeal and digital interphalangeal joints due to its attractive properties such as emission of two low energy β - particles of maximum energies 342 keV (45%) and 351 keV (55%), respectively and low (0.0014%) emission of a 110.5 keV gamma-ray, suitable for monitoring and dosimetry [1,8,9,13–15]. The low β max energy of 169 Er results in a short tissue penetration depth (~ 0.3 mm) and thus prevents radiogenic damage to the juxta-articular tissues. Besides its use in the RSV of digital joints, 169 Er can also be considered as a promising candidate for palliative care of bone pain arising out of skeletal metastases for patients having primary cancers in breast, prostate, lung etc. in their advanced stages [16]. Erbium-169 has the distinct advantage in the emission of β - particles of adequately low energy and therefore expected to have minimum bone marrow suppression on accumula- tion in skeletal lesions. Moreover, 9.4 d half-life of 169 Er provides logistic advantage for shipment to places far away from the reactors. However, cost effective availability of 169 Er in required quantity and with adequate specific activity and radionuclidic purity is a major Nuclear Medicine and Biology 41 (2014) 163–170 ⁎ Corresponding author. Fax: +91 22 25505151. E-mail address: adash@barc.gov.in (A. Dash). 0969-8051/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.nucmedbio.2013.11.009 Contents lists available at ScienceDirect Nuclear Medicine and Biology journal homepage: www.elsevier.com/locate/nucmedbio