Linked Life Data

1893374

Source:http://linkedlifedata.com/resource/pubmed/id/1893374

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1991-10-21
pubmed:abstractText
Accurate dosimetry is essential for the assessment of radioimmunotherapy. Most often studied to date has been the macroscopic dosimetry related to organ and tumor distribution of the radiolabeled antibody, but the question of microscopic dose heterogeneity is also important. To address the latter issue, we have taken an integrated approach to the pharmacology, taking into account whole-body distribution, transcapillary transport, percolation through the tumor interstitial space, antigen-antibody interaction, and antibody metabolism. The first step is to simulate the spatial antibody concentration profile in a tumor as a function of time after i.v. (e.g., bolus) injection, using reasonable values for the parameters involved. The second step is to calculate, also as a function of time, the absorbed radiation dose distribution resulting from each concentration profile. Parameter values for IgG pharmacology and a radiation point source function for 131I are used to explore the effect of antibody distribution profiles on absorbed dose in the tumor. The geometry simulated corresponds to a spherical nodule of densely packed tumor cells. Absorbed doses are calculated for radiation from a single nodule (e.g., a micrometastasis or prevascular primary tumor) and for a cubic lattice of such nodules (e.g., corresponding to nodular lymphoma). As noted in our previous studies, there is a "binding site barrier." Binding to antigen retards antibody percolation into the nodules; high antibody affinity tends to decrease percolation and give a higher absorbed dose near the surface of each nodule. Heterogeneous antibody distribution results in a heterogeneous absorbed dose. This is more apparent in the case of radiation from a single nodule than it is for radiation from within an array of nodules. Dehalogenation results in a lower absorbed dose over time, and the effect is more apparent at later times after injection. PERC-RAD, the computer program package developed for these analyses, provides a convenient and flexible way to assess the impact of macroscopic and microscopic parameters on the distribution of radioimmunoconjugates and on the consequent profile of absorbed radiation dose in tumors. This mathematical model and the general principles developed here can be applied as well to other radiolabeled biological ligands.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4821-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Integrated microscopic-macroscopic pharmacology of monoclonal antibody radioconjugates: the radiation dose distribution.
pubmed:affiliation
Laboratory of Mathematical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.