Theoretical estimation of absorbed dose to organs in radioimmunotherapy using radionuclides with multiple unstable daughters Journal Article

Authors: Hamacher, K. A.; Sgouros, G.
Article Title: Theoretical estimation of absorbed dose to organs in radioimmunotherapy using radionuclides with multiple unstable daughters
Abstract: The toxicity and clinical utility of long-lived alpha emitters such as Ac-225 and Ra-223 will depend upon the fate of alpha-particle emitting unstable intermediates generated after decay of the conjugated parent. For example, decay of Ac-225 to a stable element yields four alpha particles and seven radionuclides. Each of these progeny has its own free-state biodistribution and characteristic half-life. Therefore, their inclusion for a more accurate prediction of absorbed dose and potential toxicity requires a formalism that takes these factors into consideration as well. To facilitate the incorporation of such intermediates into the dose calculation, a previously developed methodology (model 1) has been extended. Two new models (models 2 and 3) for allocation of daughter products are introduced and are compared with the previously developed model. Model 1 restricts the transport to a function that yields either the place of origin or the place(s) of biodistribution depending on the half-life of the parent radionuclide. Model 2 includes the transient time within the bloodstream and model 3 incorporates additional binding at or within the tumor. This means that model 2 also allows for radionuclide decay and further daughter production while moving from one location to the next and that model 3 relaxes the constraint that the residence time within the tumor is solely based on the half-life of the parent. The models are used to estimate normal organ absorbed doses for the following parent radionuclides: Ac-225, Pb-212, At-211, Ra-223, and Bi-213. Model simulations are for a 0.1 g rapidly accessible tumor and a 10 g solid tumor. Additionally, the effects of varying radiolabled carrier molecule purity and amount of carrier molecules, as well as tumor cell antigen saturation are examined. The results indicate that there is a distinct advantage in using parent radionuclides such as Ac-225 or Ra-223, each having a half-life of more than 10 days and yielding four alpha particles per parent decay, in that lower doses to normal organs result for a given tumor dose in comparison to those radionuclides yielding fewer alpha particles. In model 2, which accounts for transit time through the blood, a dose of 20 Gy to a rapidly accessible 0.1 g tumor will result in a liver and kidney dose of 1.7 and 0.9 Gy, respectively from Ac-225. An equivalent dose to tumor from Ra-223 would yield a maximum normal organ dose of 0.4 and 0.3 Gy to bone and small intestines, respectively; the corresponding absorbed dose to small intestines from Pb-212 and Bi-213 is 2.2 and 3.0 Gy, respectively. © 2001 American Association of Physicists in Medicine.
Keywords: controlled study; human tissue; radiation dose; accuracy; models, biological; radiotherapy dosage; radiation injury; tumor antigen; prediction; liver; kidney; tissue distribution; dosimetry; adsorption; radioisotope; half life time; radioimmunotherapy; small intestine; radioisotopes; radiation dose distribution; dose calculation; biophysics; alpha radiation; alpha particles; actinium; astatine 211; bismuth 213; radium; biological transport, active; lead 212; humans; human; priority journal; article
Journal Title: Medical Physics
Volume: 28
Issue: 9
ISSN: 0094-2405
Publisher: American Association of Physicists in Medicine  
Date Published: 2001-09-01
Start Page: 1857
End Page: 1874
Language: English
DOI: 10.1118/1.1395026
PUBMED: 11585217
PROVIDER: scopus
Notes: Export Date: 21 May 2015 -- Source: Scopus
Altmetric Score
MSK Authors
  1. George Sgouros
    143 Sgouros