Pak. J. Pharm. Sci., Vol.27, No.4, July 2014, pp.813-818 813 Evaluation of carrier added and no carrier added 90 Y-EDTMP as bone seeking therapeutic radiopharmaceutical Muhammad Khalid 1 , Tanveer Hussain Bokhari* 2 , Mushtaq Ahmad 1 , Haq Nawaz Bhatti 3 , Munawar Iqbal 3 , Abdul Ghaffar 2 and Muhammad Imran Qadir 4 1 Isotope Production Division, Pakistan Institute of Nuclear Science and Technology, P.O. Nilore, Islamabad, Pakistan 2 Department of Chemistry, Government College University, Faisalabad, Pakistan 3 Department of Chemistry and Biochemistry, University of agriculture, Faisalabad, Pakistan 4 College of Pharmacy, Government College University, Faisalabad, Pakistan Abstract: The optimum conditions to label ethylenediaminetetramethylene phosphonate (EDTMP) compound with 90 y as a potential candidate for bone metastases therapy were investigated. Yttrium-90 is a pure β-emitter and can be obtained by 89 y (n,γ) 90 y nuclear reaction in a reactor or from an in-house generator system ( 90 sr→ 90 y). The preparation of 90 Y-EDTMPis described using 90 y, which was obtained from neutron irradiation of y 2 o 3 as well as from a laboratory scale organic resin-based 90 sr→ 90 y generator. Because of the radiolabeling yield of 90 Y-EDTMP on ligand/metal molar ratio, incubation time and ph was evaluated. Under optimum parameters, the radiolabeling yields of 90 Y-EDTMPwere <95% for no-carrier-added as well as carrier-added 90 y. The biodistribution of no-carrier-added and carrier-added 90 Y- EDTMPcomplexes in rats was identical. The results indicate that 90 y (carrier-added)-edtmp is also an effective bone pain palliation agent because of its rapid blood clearance, greater uptake in bones and little absorption in soft tissues. Keywords: Carrier-added Yttrium-90; No-carrier-added Yttrium-90; Strontium-90/Yttrium-90 generator; EDTMP; Biodistribution in rats. INTRODUCTION Nuclear medicine is a medical modality that uses radiopharmaceuticals to diagnose and treat diseases. Fruitful radiotherapy depends upon matching the radionuclide with chemistry and biological kinetics of carrier molecule. Radionuclides which decay with the emission of β-particles are rapidly becoming of great interest for cancer therapy. The debilitating and intractable pair that may accompany cancer is often produced by bone metastases, while radiotherapy is the first choice for palliative treatment for patients with limited number of lesions. Systemic radionuclide therapy with radiopharmaceuticals is preferable for extensive bone metastases with multifocal sites of pain and remains a most widely used and effective modality (Serafini, 2001). Strategies for the management of bone metastases include opiate analgesia, steroids, bisphosphonates, cytotoxic chemotherapy, external beam radiotherapy and unsealed source radiotherapy. Unsealed source radiotherapy for skeletal metastases was one of the first applications of radioisotopes in medicine and dates from more than five decades ago, when phosphorus-32 was first used. Strontium-89 was introduced in 1942 as a targeted radiotherapeutic agent for bone metastases (Pecher, 1942). Ethylenediaminetetramethylene phosphonate is a tetraphosphonate ligand and show great affinity to skeleton and osteoblastic bone metastases and various EDTMP chelates possess a significantly high stability (Goeckeler et al., 1987). Subsequently a variety of radioactively labeled EDTMP compounds have been developed and used clinically for diagnosis and treatment of osteoblastic lesions. The synthesis of EDTMP chelates with β-emitters reported in literature includes yttrium-90 [Keeling et al., 1989], rhodium-105 (Ando et al., 2000), samarium-153 (Goeckeler et al., 1987; Mushtaq et al., 1997), erbium-165 (Hassfjell et al., 1998), holmium-166 (Louw et al., 1996), lutetium-177 (Ando et al., 1998; Chakraborty et al., 2002), rhenium-188 (Oh et al., 2002; Pervez et al., 2003; Mushtaq et al., 2007). Diagnostic radionuclides, yttrium-86 (Roesch et al., 1996), technetium-99m ( Garnuszek et al., 2003; Bokhari et al., 2012; Faheem et al., 2013) and indium-111 have been reported as well (Laznicek et al., 1994). Yttrium-90 is believed to be the most useful among the radionuclides that have been employed for radiotherapeutic purposes. Yttrium-90 with half-life of 64.1 h has no accompanying gamma-ray radiation in its decay, high-energy β rays of (E βmax =2.3 MeV), and a stable Zirconium-90. 90 Y is mostly obtained from 90 Sr/ 90 Y the chromatographic generator of system. Different procedures for clean separation of 90 Y from high yielded fission product 90 Sr have been reported, the solvent extraction and ion exchange was mostly employed for its separation (Chinol et al., 1987). The 90 Y, high specific activity is achieved by the methods for radioimmunotherapy (Hnatowich et al., 1985). However users must note that parent strontium-90 (T 1/2 =28 y) gives bone marrow depression and its *Corresponding author: e-mail: tanveer.bokhari@yahoo.com