Initial observations on the effect of irradiation on the liver-specific uptake of Levovist

Abstract 

The aim of this pilot study was to see if the biodistribution of the microbubble Levovist (SHU 508 A; Schering AG, Berlin) during its liver specific phase is altered by radiotherapy. The mechanism of this liver-specific phase of this agent remains poorly understood. One way of investigating this is to see what effect radiotherapy has on liver uptake, as both Kupffer cell function and vascular endothelial integrity are selectively damaged by irradiation. The regional liver specific uptake of Levovist was evaluated in eight patients undergoing radiotherapy to the hepatic area. Ultrasound (US) sweeps were made 4 min after Levovist injection using the phase inversion mode (PIM) which is specific for microbubbles. Differences between irradiated and non-irradiated areas were observed in 2/8 subjects completing the study. Both subjective and objective evaluations in these subjects showed a significantly reduced grey scale unit in non-irradiated versus irradiated liver regions (average values 99 vs. 89, P<0.0045 and 75 vs. 62, P<0.0001). These findings are somewhat inconclusive, but given the difficulty in defining areas of irradiated and non-irradiated liver, because multiple radiotherapy portals were used in all patients, tentatively suggests a radiotherapy induced effect in at least some patients. The two likely mechanisms would be damage to the Kupffer cells and or the vascular endothelium, although the relative contribution of these is unclear.

Keywords:  Levovist, US contrast agents, Microbubbles, Liver specific phase, Late phase, Kupffer cell