OXYGENATION IN TUMORS BY MODIFIED HEMOGLOBINS

The effect of systemic injection of modified hemoglobin (Hb) prepared from bovine, human, or mouse Hb on tumor oxygenation was investigated. Hb was modified by (1) diisothiocyanatobenzenesulfonate (DIBS) to yie ld cross-linking within a tetramer; (2) glycolaldehyde (Glyal) to yiel d cross-linking between and within tetramers; (3) carboxymethylation ( Cm) to change oxygen affinity; or (4) poly(ethylene glycol) (PEG) to y ield attachment between tetramers. HGL9 (human glioma) in nude mice an d FSaII (mice fibrosarcoma) in C3H mice were used as tumor models. Dos e and time dependency were detected in the oxygenation effect by bovin e-PEG-Hb. Internal cross-linkage prolonged the half-life in the circul ation, and thus showed a significant effect. Compared to bovine-CmHb, bovine-DIBS-Hb and bovine-DIBS-CmHb were more effective. Decreasing th e oxygen affinity by Cm significantly enhanced tumor oxygenation. Huma n-DIBS-CmHb was more effective than human-DIBS-Hb. These effects were caused by oxygen carrying capacity of modified Hbs as well as hemodyna mic factors, and the injection seemed to reduce both perfusion-limited (acute) and diffusion-limited (chronic) hypoxia. (C) 1996 Wiley-Liss, Inc.