Breakthrough of 225Ac and its radionuclide daughters from an 225Ac/213Bi generator: development of new methods, quantitative characterization, and implications for clinical use.
Bisumth-213, a short-lived alpha particle emitting radionuclide, is generated from the decay of 225Ac, which has a half-life of 10 days. The development of a clinical 225Ac/213Bi generator and the preparation of a 213Bi radiolabeled antibody for radioimmunotherapy of leukemia have been reported. The 225Ac decay scheme is complex; therefore a thorough understanding of the impact of both the parent 225Ac and its daughters on radiolabeling, purification, and quantification is necessary for optimal use of the generator system. This paper reports: (i) unique new methods to measure 221Fr, 213Bi, and 209Pb, the prominent daughters of 225Ac; and (ii) a quantitative evaluation of 225Ac/213Bi generator breakthrough and the radionuclidic purity of 213Bi labeled radiopharmaceutical dose formulations. A quantitative multi-dimensional proportional scanning method was employed to distinguish and measure specific daughter radionuclides. This method combines thin layer chromatography in two perpendicular directions with attenuated collimation as a function of time for data collection and analysis. Francium-221 and 213Bi eluted differentially from the generator, and 221Fr contributed minimally to unchelated 213Bi in the reaction and final products. Lead-209 was present in the reaction solution, but not strongly bound by the chelating moiety either (i) under the 213Bi labeling reaction conditions or (ii) following chelated 213Bi decay. As a consequence of incorporating several new procedures to the operation of the generator, 225Ac breakthrough in the final product was further reduced and represented a trivial contaminant in the final drug formulations.
Ma
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Department of Pharmacology and Molecular Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
McDevitt
M R
MR
Finn
R D
RD
Scheinberg
D A
DA
D000186:Actinium / Q000302:isolation & purification* / Q000627:therapeutic use; D001729:Bismuth / Q000302:isolation & purification*; D005605:Francium / Q000302:isolation & purification; D006801:Humans; D007856:Lead Radioisotopes / Q000302:isolation & purification; D007938:Leukemia / Q000532:radiotherapy; D011854:Radiochemistry / Q000379:methods; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000302:isolation & purification*; D019275:Radiopharmaceuticals / Q000302:isolation & purification* / Q000627:therapeutic use
D007856:Lead Radioisotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D005605:Francium; D000186:Actinium; D001729:Bismuth