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Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(L-lactic acid) microspheres in healthy pigs

By M.A.D. Vente, J.F.W. Nijsen, T.C. de Wit, J.H. Seppenwoolde, G.C. Krijger, P.R. Seevinck, Albert Huisman, Bernard A. Zonnenberg, T.S.G.A.M. van den Ingh and A.D. van het Schip

Abstract

Purpose: The aim of this study is to evaluate the toxicity of\ud holmium-166 poly(L-lactic acid) microspheres administered\ud into the hepatic artery in pigs.\ud Methods: Healthy pigs (20–30 kg) were injected into the\ud hepatic artery with holmium-165-loaded microspheres\ud (165HoMS; n=5) or with holmium-166-loaded microspheres\ud (166HoMS; n=13). The microspheres’ biodistribution\ud was assessed by single-photon emission computed\ud tomography and/or MRI. The animals were monitored\ud clinically, biochemically, and (166HoMS group only) hematologically\ud over a period of 1 month (165HoMS group) or\ud over 1 or 2 months (166HoMS group). Finally, a pathological\ud examination was undertaken.\ud Results: After microsphere administration, some animals\ud exhibited a slightly diminished level of consciousness and a\ud dip in appetite, both of which were transient. Four lethal\ud adverse events occurred in the 166HoMS group due either to\ud incorrect administration or comorbidity: inadvertent delivery\ud of microspheres into the gastric wall (n=2), preexisting\ud gastric ulceration (n=1), and endocarditis (n=1). AST levels\ud were transitorily elevated post-166HoMS administration. In\ud the other blood parameters, no abnormalities were observed.\ud Nuclear scans were acquired from all animals from the\ud 166HoMS group, and MRI scans were performed if available.\ud In pigs fromthe 166HoMS group, atrophy of one or more liver\ud lobes was frequently observed. The actual radioactivity distribution\ud was assessed through ex vivo 166mHo measurements.\ud Conclusion: It can be concluded that the toxicity profile of\ud HoMS is low. In pigs, hepatic arterial embolization with\ud 166HoMS in amounts corresponding with liver-absorbed\ud doses of over 100 Gy, if correctly administered, is not\ud associated with clinically relevant side effects. This result\ud offers a good perspective for upcoming patient trials

Topics: Geneeskunde, Internal radiation therapy, Holmium, Microspheres, Liver malignancies
Year: 2008
OAI identifier: oai:dspace.library.uu.nl:1874/29977
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