Short Communication Practicality of Production of 32 P by Direct Neutron Activation for Its Utilization in Bone Pain Palliation as Na 3 [ 32 P]PO 4 K.V. Vimalnath, 1 Priyalata Shetty, 1 Sudipta Chakraborty, 1 Tapas Das, 1 Viju Chirayil, 1 H.D. Sarma, 2 K.C. Jagadeesan, 1 and P.V. Joshi 1 Abstract Large-scale production of 32 P for its clinical use in palliative care of painful bone metastasis in the form of Na 3 [ 32 P]PO 4 ( 32 P-sodium orthophosphate) has been practiced for six decades. The classical route of production of 32 P by (n,p) reaction on high purity elemental sulfur yields no-carrier-added (NCA) 32 P. Since high specific activity 32 P is not essential for the formulation of Na 3 [ 32 P]PO 4 for bone pain palliation, an alternate route of production of 32 P by direct neutron capture using elemental phosphorus target [ 31 P(n,c) 32 P] was envisaged and its suitability for use in bone pain palliation was evaluated. Toward this, irradiation of elemental red phosphorus target was carried out at a neutron flux of 8 · 10 13 n/cm 2 .s for 60 days and this yielded 32 P with a specific activity of 230 – 15 MBq/mg (6.2 – 0.4 mCi/mg) having > 99.9% radionuclidic purity. About 370–555 MBq (10–15 mCi) doses of Na 3 [ 32 P]PO 4 were formulated in sterile saline (pH 7.4) using the 32 P produced. The radiochemical purity of the formulation was found to be *99% with respect to PO 4 3 - . The formulation exhibited good in vitro stability in saline and in human serum. Biodistribution studies carried out in normal Wistar rats revealed comparable pharmacokinetic properties of the formulation prepared using (n,c) produced 32 P with that of NCA 32 P produced by (n,p) route. Besides having the advantages of simplicity in radiochemical processing and minimum radio- active waste generation, use of the proposed production route in place of the traditional 32 S(n,p) 32 P route would result in better utilization of irradiation volume of research reactors. Key words: 32 P, Na 3 [ 32 P]PO 4 , radiochemical purity, radionuclidic purity, red phosphorus Introduction P hosphorus-32 [T 1/2 = 14.26 days, E b(max) = 1.71 MeV, no c] as Na 3 [ 32 P]PO 4 has been widely used for palliation of pain arising from osseous metastases and also in the treatment of myeloproliferative diseases for the last six decades. 1–7 Routi- nely, 32 P is produced in large scale (74–740 GBq, 2–20 Ci in a batch) in research reactors by use of 32 S(n,p) 32 P reaction. This route of production yields 32 P in no-carrier-added (NCA) form. However, poor yield 32 P obtained in 32 S(n,p) 32 P process is one of the major drawbacks of this production route, since the nuclear reaction has a cross section of only 69.55 mb for fast neutrons, which usually is a small fraction of the thermal neutron flux. As a result, a large amount of elemental sulfur needs to be irradiated to get 32 P activity in adequate quantity, which eventually occupies a large irradiation volume in re- search reactors. Apart from this, the tedious and time- consuming radiochemical procedure required to separate a small quantity of 32 P from the bulk of irradiated sulfur target is another major drawback. Moreover, irradiation of natu- ral elemental sulfur also leads to the coproduction of 33 P [T 1/2 = 25.3 days, E b(max) = 249 keV, no c] through 33 S(n,p) 33 P route (r = 57.18 mb) as a radionuclidic impurity. The production of 32 P in research reactor could also be carried out by thermal neutron activation of natural ele- mental phosphorus target material. However, this route of production yields low specific activity 32 P, since the 31 P(n,c) 32 P process has a poor thermal neutron capture cross section of 172 mb. It is worth mentioning that unlike natural sulfur, natural phosphorus is mononuclidic in 31 P, which rules out the formation of any other activation products as radionuclidic impurities. Theoretically, there is a possibility 1 Radiopharmaceuticals Division and 2 Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India. Address correspondence to: Sudipta Chakraborty; Radiopharmaceuticals Division, Bhabha Atomic Research Centre; Mumbai 400085, India E-mail: sudipta@barc.gov.in CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS Volume 00, Number 00, 2013 ª Mary Ann Liebert, Inc. DOI: 10.1089/cbr.2012.1335 1