Murine S factors for liver, spleen, and kidney

Katherine S. Kolbert, Timotheus Watson, Cornelia Matei, Su Xu, Jason A. Koutcher, George Sgouros

Research output: Contribution to journalArticlepeer-review

Abstract

Preclinical evaluation of new radiopharmaceuticals is performed in animal systems before testing is started in humans. These studies, often performed in murine or other rodent models, are important in understanding the relationship between absorbed dose and response, which can be translated to preclinical results for humans. In performing such calculations, either electrons are assumed to deposit all of their energy locally or idealized models of mouse anatomy are used to determine absorbed fractions. Photon contributions are generally considered negligible. To improve the accuracy of such absorbed dose calculations, mouse-specific S factors for 131I, 153Sm, 32P, 188Re, and 90Y have been generated, and the photon and electron portions have been tabulated separately. Absorbed fractions for 5 monoenergetic electrons, ranging in energy from 0.5 to 2 MeV, are also provided. Methods: Female athymic mouse MR images were obtained on a 4.7-T MRI device. Fifteen T1-weighted, 1.5-mm-thick slices (0.5-mm gap) were collected. Using a previously developed software package, 3-dimensional Internal Dosimetry (3D-ID), organ contours were drawn to obtain a 3-dimensional representation of liver, kidneys, and spleen. Using a point-kernel convolution, the mean absorbed dose to each organ from the individual contributions of each source organ were calculated. S factor equivalent values were obtained by assuming a uniform distribution of radioactivity in each organ. Results were validated by comparing 3D-ID generated electron S factors for different-sized spheres with published data. Depending on matrix size, sphere size, and radionuclide, 1% (2562 matrix) to 18% (642 matrix) agreement was obtained. Results: S factor values were calculated for liver, spleen, and right and left kidneys. Cross-organ electron-absorbed fractions of up to 0.33 were obtained (e.g., 90Y right kidney to liver). Comparisons between S factor values and values obtained assuming complete absorption of electron energy yielded differences of more than 190% ( 90Y spleen self-dose). Conclusion: The effect of cross-organ and self-absorbed dose is dependent on emission energy and organ geometry and should be considered in murine dose estimates. The approach used to generate these S factors is applicable to other animal systems and also to nonuniform activity distributions that may be obtained by small-animal SPECT or PET imaging or by quantitative autoradiography.

Original languageEnglish (US)
Pages (from-to)784-791
Number of pages8
JournalJournal of Nuclear Medicine
Volume44
Issue number5
StatePublished - May 2003
Externally publishedYes

Keywords

  • Dosimetry
  • I
  • Monoenergetic electron
  • Murine model
  • P
  • Re
  • S factors
  • Sm
  • Y

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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