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Many human cancers predominantly metastasize to the bone which causes bone pain and other symptoms. However, the management of bone metastases is challenging. Radionuclide therapy using low-energy beta-emitting radionuclides has yielded encouraging results. The aim of this therapy is to deliver the maximum dose to the metastatic sites but a minimal dose to the normal tissue. Samarium-153 [153Sm]Sm-Ethylenediamine tetramethylene phosphonate (EDTMP) is an FDA and European Medicine Agency approved (Quadramet) radionuclide and is widely used for bone pain palliation. 153Sm is reactor produced, and the presence of europium impurities is thus unavoidable. This in turn causes an increase in the hospital radioactive waste burden and in radiation absorbed doses to the patients, and therefore it is a concern. The effective removal of these impurities is thus highly desirable before its administration to the patients. In this article, we present a detailed review of the various methods described in the literature for separation of 153Sm and Eu, that is solvent extraction, ion-exchange chromatography, electrochromatography, electrochemical separation and supported ionic liquid phase.

Skeletal uptake of radiolabeled‐1, 4, 7, 10‐tetraazacyclododecane‐1, 4, 7, 10‐tetramethylene phosphoric acid (e.g., 177Lu‐DOTMP) complex, is used for bone pain palliation. The moderate energy of β‐emitting .15em177Lu false(normalT1/2=6.7 d,normalEβmax=497 keVfalse) has been considered as a potential radionuclide for development of the bone‐seeking radiopharmaceutical. Since the specific activity of the radiolabeled carrier molecules should be high, the “no‐carrier‐added radionuclides” have significant roles in nuclear medicine. Many researchers illustrated no‐carrier‐added 177Lu production; among these separation techniques such as ion exchange chromatography, reversed phase ion‐pair, and electrochemical method, extraction chromatography has been considered more capable than other methods. In order to optimize the conditions, some effective factors on separation of Lu/Yb were investigated by EXC. The NCA 177Lu, produced by this method, was mixed with 300μ1 of DOTMP solution (20 mg in 1 mL of 0.5 M NaHCO3, pH=8) and incubated under stirring at room temperature for 45 min. Radiochemical purity of the 177Lu‐DOTMP complex was determined using radio‐thin‐layer chromatography (RTLC) method. The complex was injected to wild‐type rats and biodistribution was then studied for seven days. The NCA 177Lu was produced with specific activity of 48 Ci/mg and with a radinuclidic purity of 99.99% through irradiation of enriched 176Yb target (1 mg) in a thermal neutron flux of 4×1013 n.cm−2.normals−1 for 14 days. 177Lu‐DOTMP was obtained with high radiochemical purities (>98%) under optimized reaction conditions. The radiolabeled complex exhibited excellent stability at room temperature. Biodistribution of the radiolabeled complex studies in rats showed favorable selective skeletal uptake with rapid clearance from blood along with insignificant accumulation within the other nontargeted organs.PACS number(s): 87.57.un, 87.57.uq

In this paper, the metal organic framework (MOF) concept is contributed to rearrange the bone-seeking agent composed of carrier-free lutetium-177 (Lu-177), 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraaminomethylenephosphonate (DOTMP) and cupper (II) (Cu (II)) for preparation of a potential agent for treatment of bone metastases. The product was characterized (infra-red spectroscopy, IR, and X-ray diffraction analysis) and quality-controlled (radio-thin layer chromatography, (RTLC)). The stability and in vitro hydroxyapatite binding was checked up to 1.5 month at 37 °C in human serum. Radio-MOF crystals and radio-MOF particles that were obtained by varying the synthesizing conditions (including pH and temperature) showed similar IR patterns and similar elemental analysis results. The final product was synthesized at pH = 8, stirring at room temperature (yield >99%, RTLC, particle size: 90 ± 20 nm). Biodistribution study experiments showed interesting bone-seeking (%ID/g: 8.5%) affinity of the prepared formula with no significant liver or lung uptake. Also high accumulation of radio-complex in bone tissue was estimated by the modeling of the radiation dose delivery using radiation dose assessment resource software. This novel radio-MOF with promising therapeutic results is the first study of the usage of the MOF concept to provide a high payload of Lu-177 for treatment of bone metastases. As it was expected, the most important outcome of the paper was higher bone-uptake rates rather than conventional 177Lu-DOTMP.