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Nonuniformity of Tumor Dose in Radioimmunotherapy

Cancer Research Campaign Laboratories, Department of Medical Oncology, Charing Cross Hospital, London, UK
Division of Experimental, Pathology and Therapeutics, MRC Radiobiology Unit, Harwell, Didcot, UK

Correspondence: For reprints contact: J.L. Humm, PhD, Joint Center for Radiation Therapy and Dept. of Radiation Therapy, Harvard Medical School, 50 Binney St., Boston MA 02115.

ABSTRACT

The conventional approach to calculating tumor radiation dose from internally administered radioisotopes is by the MIRD schema. The raw input data for such dose calculations is obtained by immunoscintigraphic methods, PLANAR or SPECT imaging. Limitations in the spatial resolution of these techniques can lead to a considerable underestimate of the gross variation in tumor dose. The use of radiolabeled monoclonal antibodies for therapy can result in large nonuniformities in tumor dose. This paper discusses how antibody distribution can influence the energy deposition in the nuclei of target cells. Heterogeneity of antibody binding will lead to an expected decrease in the effectiveness of the radiation delivered. However, enhanced cell killing is possible if the radiolabeled Ab binds to the cell surface membrane and may be further enhanced if the Ab is internalized. Calculations are presented for two cases: (a) a three-dimensional random packing arrangement of cells as a model of the astructural nondifferentiated form seen in some tumors, and (b) differentiated carcinoma of the colon with the cells in tubules. Results for the magnitude of the mean energy deposition to individual cell nuclei from: (a) cell membrane bound ²¹¹At, ¹⁹⁹Au, ¹³¹I, and ⁹⁰Y-labeled Abs, and (b) a uniform distribution of these sources, as a function of internuclear distance for the two histologies are presented. Energy deposition in tumor cell nuclei from membrane bound radiolabeled antibody may be several times greater than estimated with the assumption of a uniform source distribution.

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