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Inhomogeneous Deposition of Radiopharmaceuticals at the Cellular Level: Experimental Evidence and Dosimetric Implications

Department of Radiology, Harvard Medical School, Shields Warren Radiation Laboratory, Boston, Massachusetts
Department of Anatomy and Cellular Biology, Harvard Medical School, Boston, Massachusetts
Department of Radiation Therapy, Harvard Medical School, Boston, Massachusetts

Correspondence: For reprints contact: A. I. Kassis, PhD, Department of Radiology, Harvard Medical School, Shields Warren Radiation Laboratory, 50 Binney St., Boston, MA 02115.

ABSTRACT

We have undertaken an experimental examination of the conventional internal dosimetry assumptions of homogeneity of radionuclide deposition in tissues. The distribution of radiolabeled Microlite has been quantitated in mouse liver at the millimeter (multicellular) and the micrometer (cellular) levels. Measurements of radioactivity in 1-mm³ tissue samples indicate homogeneous radionuclide distribution; those derived from autoradiographs of 0.5-µm tissue sections show that, relative to other cells, the colloid was concentrated 200- to 1000-fold in liver macrophages. The dosimetric implications of such inhomogeneous radionuclide distribution in human liver, where similar radionuclide distribution is expected, are discussed on the basis of a recently developed model for calculating the dose at the cellular level, and the estimates are compared to conventional internal dosimetry predictions. It is demonstrated that during routine diagnostic examinations with ^99mTc-Microlite, conventional dosimetry underestimates the dose to labeled human liver cells by factors of 8–30.

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