Production and quality control ¹⁷⁷Lu (NCA)—DOTMP as a potential agent for bone pain palliation

Abstract

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

Preparation and Evaluation of 177Lu-TDTMP: A Potential Theranostic Agent for Bone Metastases

“…177 Lu also emits adequate energy ɣphotons [113 KeV (6.4 %) and 208 KeV (11%)] in low abundance which is ideally suited for carrying out scintigraphic studies and dosimetric evaluation, thereby enabling diagnosis and monitoring in vivo localization in addition to therapeutic effect [1,4]. The optimal half-life of 177 Lu is longer than 153 Sm and 186 Re providing logistic advantages for facilitating supply to places far away from the reactors and providing the required time period for separation chemical processing, radiopharmaceuticals production and quality control and administration to patient [16]. It is also much shorter than 89 Sr and 32 P hence offers a faster rate dose delivery for therapeutic purposes [5].…”

Radiochemical processing of nuclear-reactor-produced radiolanthanides for medical applications

“…In addition to ion-exchange and electrochemical methods, the use of extraction chromatography techniques have been explored widely [1,60,140,179]. Knapp et al developed a one-step extraction chromatography separation process making use of the commercial available LN resin (Eichrom), which comprises di-(2-ethylhexyl) phosphoric acid (HDEHP) [1,53,140,180].…”

“…Horwitz et al further explored this extraction chromatography technique by making use of an extraction chromatographic resin containing 2-ethylhexyl 2-ethylhexylphosphonic acid (HEH[EHP]) sorbed onto a 25-53 mm Amberchrom CG-71 substrate (i.e. LN2 resin, Eichrom) [60,178,179]. Dilute HNO 3 solutions were used to elute the target material on the LN2 column.…”