Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study

Intra-arterial administration of beta-emitting particles that become trappe d in the vascular bed of a tumour and remain there while delivering high do ses, represents a unique approach in the treatment of both primary and meta static liver rumours. Studies on selective internal radiation therapy of co lorectal liver metastases using yttrium-90 glass microspheres have shown en couraging results. This study describes the biodistribution of 40-mum poly lactic acid microspheres loaded with radioactive holmium-166, after intra-a rterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed > 95% retention of injected act ivity in the liver and its resident tumour, The average activity detected i n other tissues was less than or equal to0.1%ID/g, with incidental exceptio ns in the lungs and stomach. Very little Ho-166 activity was detected in ki dneys (<0.1%ID/g). thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver rati o of 6.1 +/-2.9 for rats with tumour (n=15) versus 0.7 +/-0.5 for control r ats (n=6, P <0.001). These ratios were not significantly affected by the us e of adrenaline. Histological analysis showed that five times as many large (> 10) and medium-sized (4-9) clusters of microspheres were present within tumour and peritumoural tissue, compared with normal liver. Single microsp heres were equally dispersed throughout the tumour, as well as normal liver parenchyma.