LOCALIZED BETA DOSIMETRY OF I-131-LABELED ANTIBODIES IN FOLLICULAR LYMPHOMA

The purpose of this study is to assess the multicellular dosimetry of I-131-labeled antibody in follicular lymphoma based on histological measurements on human tumor biopsy tissue. Photomicrographs of lymph node specimens were analyzed by first-order treatment to determine the mean values and statistical variations of the radii of follicles (260 +/- 90-mu-m), interfollicular distances (740 +/- 160-mu-m), and the number density of follicles [60 +/- 18 in a volume of (2 x 1480-mu-m)3]. Based on these measurements, two geometrical models were developed for localized beta dosimetry. The first, a regular cubic lattice model, assumes no variation in follicular radius of follicles and interfollicular distance. The second, a randomized distribution model, is a more complicated but more realistic representation of observed histological specimens. In this model, Monte Carlo methods were used to reconstruct the spatial distribution of follicles by stimulating the distribution of the radii of follicles, interfollicular distances, and the number density of follicles. Dose calculations were performed using Berger's point kernels for absorbed-dose distribution for beta particles in water, assuming the I-113-labeled antibodies as point sources. It was assumed that the activity concentration of the labeled antibody within the follicles was ten times the activity concentration in the interfollicular spaces. The spatial distribution of localized dose was calculated for a tumor having an average dose of 40 Gy. The localized dose was found to be highly nonuniform, ranging from 20 to 90 Gy, and varying by a factor of about 2 from the average tumor dose. Most of the tissue (70%-80% by volume) was found to receive a lower dose than the average tumor dose. No significant difference in localized dose distribution was found between the regular cubic lattice model and the randomized distribution model, suggesting that sometimes a simple geometrical model may be adequate as a starting point for dosimetry of more complex situations. Finally, the localized dose distribution is discussed in terms of its usefulness for extracting information such as the mean dose, the spatial variation of dose, and the fraction of tissue receiving various absorbed doses. An approach for applying localized dosimetry to improve the estimated cell-killing efficiency is suggested.