Breakthrough of 225Ac and its radionuclide daughters from an 225Ac/213Bi generator: Development of new methods, quantitative characterization, and implications for clinical use Journal Article

  

Authors:	Ma, D.; McDevitt, M. R.; Finn, R. D.; Scheinberg, D. A.
Article Title:	Breakthrough of 225Ac and its radionuclide daughters from an 225Ac/213Bi generator: Development of new methods, quantitative characterization, and implications for clinical use
Abstract:	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. © 2001 Elsevier Science Ltd. All rights reserved.
Keywords:	leukemia; unclassified drug; methodology; radiopharmaceuticals; information processing; data analysis; radiopharmaceutical agent; radioisotope; radioimmunotherapy; radioisotopes; isolation and purification; technique; thin layer chromatography; radioisotope decay; chelation; radiochemistry; characterization; bismuth; 225ac; actinium; drug products; actinium 225; bismuth 213; purification; francium; francium 221; attenuation; lead; chromatography; generator; humans; human; priority journal; article; alpha emitter; 213bi; radionuclide breakthrough; radiopharmaceutical dose formulations; lead 209; lead radioisotopes
Journal Title:	Applied Radiation and Isotopes
Volume:	55
Issue:	5
ISSN:	0969-8043
Publisher:	Pergamon-Elsevier Science Ltd
Date Published:	2001-11-01
Start Page:	667
End Page:	678
Language:	English
DOI:	10.1016/s0969-8043(01)00062-8
PUBMED:	11573800
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0034742441&partnerID=40&md5=cc1d261316ae11f25141fb4e28ebb667
Notes:	Export Date: 21 May 2015 -- Source: Scopus

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