In vivo determination of cell cycle kinetics of non-Hodgkin's lymphomas using iododeoxyuridine and bromodeoxyuridine

Abstract

Using sequential infusions of two S-phase-specific drugs, iododeoxyuridine and bromodeoxyuridine, we have developed an in vivo method for determining the labeling index (LI), the S-phase duration (Ts), and total cell cycle times (Tc) of non-Hodgkin's lymphomas. In nine non-Hodgkin's lymphomas studied, the LI ranged from 1.5% in a follicular small cleaved-cell lymphoma to 29.6% in a diffuse large-cell lymphoma. The Ts ranged from 16 hr in a large-cell lymphoma (immunoblastic type) to 117 hr in a follicular small cleaved-cell lymphoma. The Tc varied from 69 hr in a large-cell lymphoma (immunoblastic type) to over 1000 hr in all low-grade lymphomas studied. Immunohistochemical methods using anti-BrdU antibodies were used to detect cell incorporation of the two S-phase-specific drugs. In this manner, cell cycle times could be calculated while the architecture of the tumor specimen was preserved. Difficulties in using this methodology, specifically in the calculation of the growth fraction and total cell cycle times, are pointed out. This in vivo method does, however, allow for Ts calculations independent of growth fraction considerations. Correlations of cell cycle data with various biological and clinical factors await further patient follow-up.