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

Eur J Nucl Med Mol Imaging. 2008 Jul;35(7):1259-71. doi: 10.1007/s00259-008-0747-8. Epub 2008 Mar 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 ((165)HoMS; n=5) or with holmium-166-loaded microspheres ((166)HoMS; n=13). The microspheres' biodistribution was assessed by single-photon emission computed tomography and/or MRI. The animals were monitored clinically, biochemically, and ((166)HoMS group only) hematologically over a period of 1 month ((165)HoMS group) or over 1 or 2 months ((166)HoMS 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 (166)HoMS 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-(166)HoMS administration. In the other blood parameters, no abnormalities were observed. Nuclear scans were acquired from all animals from the (166)HoMS group, and MRI scans were performed if available. In pigs from the (166)HoMS group, atrophy of one or more liver lobes was frequently observed. The actual radioactivity distribution was assessed through ex vivo (166m)Ho measurements.

Conclusion: It can be concluded that the toxicity profile of HoMS is low. In pigs, hepatic arterial embolization with (166)HoMS 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catheterization
  • Embolization, Therapeutic / adverse effects*
  • Embolization, Therapeutic / methods*
  • Female
  • Hepatic Artery* / anatomy & histology
  • Holmium / administration & dosage
  • Holmium / pharmacokinetics
  • Holmium / therapeutic use
  • Holmium / toxicity*
  • Humans
  • Lactic Acid / administration & dosage
  • Lactic Acid / therapeutic use
  • Lactic Acid / toxicity*
  • Liver / pathology
  • Liver / radiation effects
  • Liver Neoplasms / radiotherapy
  • Magnetic Resonance Angiography
  • Microspheres
  • Polyesters
  • Polymers / administration & dosage
  • Polymers / therapeutic use
  • Polymers / toxicity*
  • Radioisotopes / administration & dosage
  • Radioisotopes / pharmacokinetics
  • Radioisotopes / therapeutic use
  • Radioisotopes / toxicity*
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Radiopharmaceuticals / toxicity
  • Radiotherapy Dosage
  • Swine
  • Tissue Distribution


  • Polyesters
  • Polymers
  • Radioisotopes
  • Radiopharmaceuticals
  • Lactic Acid
  • poly(lactide)
  • Holmium