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

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

Vente, M.A.D.
Nijsen, J.F.W.
De Wit, T.C.
Seppenwoolde, J.H.
Krijger, G.C.
Seevinck, P.R.
Huisman, A.
Zonneneberg, B.A.
Van den Ingh, T.S.G.A.M.
Van het Schip, A.D.

Applied Sciences

Department of Radiation, Radionuclides and Reactors

2008-03-11

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

Internal radiation therapy
Holmium
Microspheres
Liver malignancies

http://resolver.tudelft.nl/uuid:6d2eeab3-1186-4ba9-87b0-81fc6de1d13d

Springer

1619-7089

European journal of nuclear medicine and molecular imaging, 35 (7)

Institutional Repository

journal article

(c) 2008 The Authors