Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody Journal Article

   

Authors:	Schwartz, J.; Jaggi, J. S.; O'Donoghue, J. A.; Ruan, S.; Mcdevitt, M.; Larson, S. M.; Scheinberg, D. A.; Humm, J. L.
Article Title:	Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody
Abstract:	Clinical therapeutic studies using 225Ac-labeled antibodies have begun. Of major concern is renal toxicity that may result from the three alpha-emitting progeny generated following the decay of 225Ac. The purpose of this study was to determine the amount of 225Ac and non-equilibrium progeny in the mouse kidney after the injection of 225Ac-huM195 antibody and examine the dosimetric consequences. Groups of mice were sacrificed at 24, 96 and 144 h after injection with 225Ac-huM195 antibody and kidneys excised. One kidney was used for gamma ray spectroscopic measurements by a high-purity germanium (HPGe) detector. The second kidney was used to generate frozen tissue sections which were examined by digital autoradiography (DAR). Two measurements were performed on each kidney specimen: (1) immediately post-resection and (2) after sufficient time for any non-equilibrium excess 213Bi to decay completely. Comparison of these measurements enabled estimation of the amount of excess 213Bi reaching the kidney (γ-ray spectroscopy) and its sub-regional distribution (DAR). The average absorbed dose to whole kidney, determined by spectroscopy, was 0.77 (SD 0.21) Gy kBq-1, of which 0.46 (SD 0.16) Gy kBq-1 (i.e. 60%) was due to non-equilibrium excess 213Bi. The relative contributions to renal cortex and medulla were determined by DAR. The estimated dose to the cortex from non-equilibrium excess 213Bi (0.31 (SD 0.11) Gy kBq-1) represented ∼46% of the total. For the medulla the dose contribution from excess 213Bi (0.81 (SD 0.28) Gy kBq-1) was ∼80% of the total. Based on these estimates, for human patients we project a kidneyabsorbed dose of 0.28 Gy MBq-1 following administration of 225Ac-huM195 with non-equilibrium excess 213Bi responsible for approximately 60% of the total. Methods to reduce renal accumulation of radioactive progeny appear to be necessary for the success of 225Ac radioimmunotherapy. © 2011 Institute of Physics and Engineering in Medicine.
Journal Title:	Physics in Medicine and Biology
Volume:	56
Issue:	3
ISSN:	0031-9155
Publisher:	IOP Publishing Ltd
Date Published:	2011-02-07
Start Page:	721
End Page:	733
Language:	English
DOI:	10.1088/0031-9155/56/3/012
PROVIDER:	scopus
PMCID:	PMC3034478
PUBMED:	21220845
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-79551705078&partnerID=40&md5=e4450a6e1cf05fb973dfcec7f0e426d4
Notes:	--- - "Export Date: 4 March 2011" - "CODEN: PHMBA" - "Source: Scopus"

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