Erbium-169 labeled hydroxyapatite particulates for use in radiation synovectomy of digital joints – a preliminary investigation

Abstract

Erbium-169 [ 1/2 = 9.4 d, (max) = 342 keV (45%) and 351 keV (55%), = 110.5 KeV (0.0014%)] is the most preferred radionuclide for radiation synovectomy (RSV) of digital joints. Radiolabeled particulates of appropriate size, wherein the radionuclide is irreversibly attached to the preformed particles, offer distinct advantages as the radiopharmaceuticals for use in RSV over other radiotherapeutic agents in terms of minimal leakage of radioactivity from the joint cavity. Hyroxyapatite (HA) particles, regarded as one of the most suitable carrier moiety for radiosynoviortheses applications, have been envisaged for labeling with 169 Er with an aim to developing an agent for RSV of digital joints. Erbium-169 was produced with a specific activity of 415 ± 23 MBq/mg and radionuclidic purity of 99.22 ± 0.17% (both at the end of bombardment) by thermal neutron irradiation of enriched (98.2% in 168 Er) erbium target at a flux of ∼ 8 × 10 13 n/cm 2 s for 21 d. HA particles (1-10 m size), synthesized in-house, were labeled with 169 Er in high yield and radiochemical purity (> 99%) using 5 mg of HA particulates at pH 7.5. The radiolabeled particulates showed excellent in vitro stability in normal saline and human serum. Biodistribution and imaging studies (using 171 Er-HA) carried out in normal Wistar rats following intra-articular injection of 169 Er-HA particulates in the knee joint showed near-complete retention of injected radioactivity within the synovial cavity with almost no activity leaching out to the other organs/tissue.

Barium titanate microparticles as potential carrier platform for lanthanide radionuclides for their use in the treatment of arthritis

“…[1][2][3][4][5][6] The key determinants for the success of RSV are the selection of an appropriate radionuclide and a biocompatible carrier platform which results in robust and irreversible binding with the radionuclide. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] This is attributed to the availability of a package of therapeutically useful radionuclides among lanthanide elements having a wide range of energy (0.34-2.28 MeV) of β − emission along with other desirable decay characteristics. 2,3,7-9 As for example, radionuclide emitting β − having maximum energy more than 1.5 MeV would be suitable for knee and hip joints, while medium energy β − emitters (maximum energy 0.5-1.0 MeV) would be suitable for ankle, elbow, and wrist joints and low energy β − emitters (maximum energy less than 0.5 MeV) for finger joints.…”

“…2,3,7-9 As for example, radionuclide emitting β − having maximum energy more than 1.5 MeV would be suitable for knee and hip joints, while medium energy β − emitters (maximum energy 0.5-1.0 MeV) would be suitable for ankle, elbow, and wrist joints and low energy β − emitters (maximum energy less than 0.5 MeV) for finger joints. 7,10,11,15,19,20 In the present work, our aim was to put forward an innovative and effective carrier platform on which lanthanide ions can be easily loaded and the loaded particles of appropriate size could be used to deliver cytotoxic dose to the diseased synovium after loco-regional administration. Based on these considerations, a plethora of therapeutic radionuclides have been proposed and clinically utilized in RSV, among which radionuclide of lanthanide elements such as 90 Y (yttrium is considered as a pseudolanthanide), 153 Sm, 165 Dy, 166 Ho, 169 Er, and 177 Lu (Table 1) are prominent ones.…”

“…Based on these considerations, a plethora of therapeutic radionuclides have been proposed and clinically utilized in RSV, among which radionuclide of lanthanide elements such as 90 Y (yttrium is considered as a pseudolanthanide), 153 Sm, 165 Dy, 166 Ho, 169 Er, and 177 Lu ( Table 1) are prominent ones. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] This is attributed to the availability of a package of therapeutically useful radionuclides among lanthanide elements having a wide range of energy (0.34-2.28 MeV) of β − emission along with other desirable decay characteristics. Treatment of the chronic inflammatory disease affecting different joints of human body (viz.…”

“…Additionally, all these radionuclide can be produced in required quantity and adequate radionuclidic purity in a nuclear reactor with moderate thermal neutron flux. 7,10,11,15,19,20 In the present work, our aim was to put forward an innovative and effective carrier platform on which lanthanide ions can be easily loaded and the loaded particles of appropriate size could be used to deliver cytotoxic dose to the diseased synovium after loco-regional administration. This single carrier platform would result in a series of radiolanthanide-loaded particulates which can be used for different joints of human body based on the energy of β − emission of the radionuclide ( 166 Ho for knee and hip, 153 Sm for ankle and elbow, 177 Lu for elbow and wrist, 169 Er for finger).…”

Radiolanthanide-loaded agglomerated Fe3O4nanoparticles for possible use in the treatment of arthritis: formulation, characterization and evaluation in rats

“…1 Ablation of the synovium can be accomplished through a number of surgical and non-surgical procedures including laser surgery, use of chemicals such as osmic acid rifampicin, and use of ionizing radiation by intra-articular administration of b À emitting radionuclides in a suitable chemical formulation. 2,[11][12][13][14][15][16][17][18][19][20][21][22][23][24] This is principally due to the availability of a wide variety of therapeutically useful b À emitting radionuclides among lanthanide elements having a wide range of energy (0.34-2.28 MeV). [2][3][4][5][6][7][8][9] While a myriad of factors contribute to the utility of RSV, selection of an appropriate b À emitting radionuclide of optimum tissue penetration range along with desirable radioactive decay a Isotope Production and Applications Division, Bhabha Atomic Research Centre, characteristics is a key determinant that underpins its success.…”