PREPARATION AND EVALUATION OF A NEW RADIOPHARMACEUTICAL FOR RADIOSINOVECTOMY 111Ag LABELED HYDROXYAPATITE HA PARTICLES
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Slide 1 :
PREPARATION AND EVALUATION OF A NEW RADIOPHARMACEUTICAL FOR RADIOSINOVECTOMY : 111Ag LABELED HYDROXYAPATITE (HA) PARTICLES
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SANKHA CHATTOPADHYAY1, K. V. VIMALNATH2, SUJATA SAHA2, ARUNA KORDE2, SUJIT PAL3 and M. K. DAS1 1. RADIOPHARMACEUTICALS LAB., BRIT, VECC, 1/AF, BIDHAN NAGAR, KOLKATA-64. 2. RADIOPHARMACEUTICALS DIVISION, BARC, MUMBAI-85. 3. ANALYTICAL DIVISION, BARC, VECC, 1/AF, BIDHAN NAGAR, KOLKATA-64.
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INTODUCTION Rheumatoid arthritis is an ubiquitous incapacitating disease that places substantial demands on health care resources. The characteristic disease manifestations of RA are joint pain, swelling and reduced mobility as a result of the synovial tissue inflammation.
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Any synovial joint in the body can be affected by the disease.
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Radiosynovectomy It consists of intra-articular injection of beta-emitting radionuclide in colloidal or particulate form, which comes into contact with synovium. Compared to surgical synovectomy, the radiation therapy is simpler and less traumatic, hospitalization time is shorter; cost is lower and duration of relief is comparable.
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Ideal radionuclide Pure beta-emitter or beta emitter with minimal gamma emissions. 5 mm < Tissue penetration < 10 mm Short half-life Low cost Chemically pure Non-toxic Radionuclide
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Radionuclides Used / Potential for Radiation Synovectomy
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Ideal particulate carrier It must be taken up by synovial tissue. It must form a stable complex with radionuclide. It must be prepared easily and reproducibly. Non-toxic. Non- allergenic. Particulate carrier
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SILVER-111 PRODUCTION Target material Nuclear Reaction Thermal neutron flux Irradiation time 7 days natPd (Palladium foil) 9 x1013 n/cm2/s EXPERIMENTAL
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Silver -111 Nitrate Radioactive solution of no-carrier-added 111Ag in nitric acid was obtained through anion exchange separation of neutron irradiated palladium at Radiochemical Section, Radiopharmaceutical Division, BARC,Mumbai. Hydroxyapatite particles (200-400mesh) were synthesized and characterized by following the reported method. Hydroxyapatite particles
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Preparation of 111Ag-hydroxyapatite 111Ag-nitrate solution in nitric acid was neutralized by adding saturated bicarbonate solution between pH 2.0 - 7.0. 10-20mg Hydroxyapatite (200- 400 mesh) particulate was suspended with stirring and kept stirring for 30 min, at room temperature. Radiolabeled particles were rinsed with saline and separated by centrifugation (5 min at 2000 rpm) and labelling efficiency was determined. The particulates were resuspended in 1 ml of saline.
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Labelling efficiency The radioactive mixture was transferred to a centrifuge tube using 4 ml of saline to rinse, centrifuged at 2000 rpm for 5 minutes. The supernatant was then transferred to another tube. Measurements of radioactivity were made and labelling efficiency was calculated as percentage of initial activity. Radiochemical purity : ITLC / SG – 0.05M Cysteine (pH:9) In vitro stability : 111Ag-HA incubated in normal saline/ phosphate buffer at room temperature upto 7 days. Quality control
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Biological studies The biological evaluation of 111Ag-HA was studied by injecting ~1.0 mCi of 111Ag preparation in one of the knee joints in normal white New Zealand rabbit and recording gamma images at three time intervals using a single head digital gamma camera. Results and Discussion Labeling Yield (pH 2-7) over 97% Radiochemical Purity over 99% In-vitro Stability Highly Stable
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80 100 120 140 160 mm TLC 80 100 120 140 160 mm 5 10 15 20 25 30 35 40 45 50 C/mm Thin Layer Chromatogram of 111AgCl 80 100 120 140 160 mm TLC 80 100 120 140 160 mm 10 20 30 40 50 60 70 C/mm Thin Layer Chromatogram of 111AgHA Rf 111AgHA : 0.0 Rf 111AgCl : 0.9-1.0
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Gamma-ray images of the normal knee joint of rabbit, injected with 111Ag-HA particles. 15min post injected 5days post injected 24hrs post injection
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SUMMARY Because of production feasibility and suitable nuclear property,111Ag has potentiality for radio-synovectomy of joints that are not too large. Hydroxyapatite, Ca10(PO4)6(OH)2 is one of the preferred particulates for this application for its excellent biocompatibility. 111Ag-HA particles were prepared with high labeling yield (>97%)and differentiated from 111AgCl by ITLC-SG. It showed excellent in-vitro stability. Preliminary imaging studies in normal rabbits are indicative of localization of 111Ag-HA in knee joint. It is therefore concluded that 111Ag-HA may be a candidate for radio-synovectomy.
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ACKNOWLEDGEMENT The authors are thankful to Dr. A. K. Kohli, Chief Executive, Board of Radiation and Isotope Technology, DAE, Mumbai, India and Meera Venkatesh, Head, Radiopharmaceuticals Division, BARC, Trombay, Mumbai, India for their support. The authors are also grateful to Dr. H. D. Sarma, Head, Radiation Biology Division, BARC, Mumbai, India for the help in carrying out gamma images.
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