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 trapped in the vascular bed of a tumour and remain there while delivering high doses, represents a unique approach in the treatment of both primary and metastatic liver tumours. Studies on selective internal radiation therapy of colorectal liver metastases using yttrium-90 glass microspheres have shown encouraging results. This study describes the biodistribution of 40-microm poly lactic acid microspheres loaded with radioactive holmium-166, after intra-arterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed >95% retention of injected activity in the liver and its resident tumour. The average activity detected in other tissues was < or =0.1%ID/g, with incidental exceptions in the lungs and stomach. Very little 166Ho activity was detected in kidneys (<0.1%ID/g), thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver ratio of 6. 1+/-2.9 for rats with tumour (n=15) versus 0.7+/-0.5 for control rats (n=6; P<0.001). These ratios were not significantly affected by the use 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 microspheres were equally dispersed throughout the tumour, as well as normal liver parenchyma.
Nijsen
F
F
Department of Nuclear Medicine, University Medical Center, Utrecht, The Netherlands. F.Nijsen@ng.azu.nl
Rook
D
D
Brandt
C
C
Meijer
R
R
Dullens
H
H
Zonnenberg
B
B
de Klerk
J
J
van Rijk
P
P
Hennink
W
W
van het Schip
F
F
D000818:Animals; D001345:Autoradiography; D005079:Excipients; D006695:Holmium / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019344:Lactic Acid; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008863:Microspheres; D011091:Polyesters; D011108:Polymers; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014915:Whole-Body Counting
D005079:Excipients; D011091:Polyesters; D011108:Polymers; D011868:Radioisotopes; D019344:Lactic Acid; C033616:poly(lactide); D006695:Holmium