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Neutron-Activated Holmium-166-Poly (L-Lactic Acid) Microspheres: A Potential Agent for the Internal Radiation Therapy of Hepatic Tumors

Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy and Division of Nuclear Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky

Correspondence: For reprints contact: Michael Jay, PhD, Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082.

ABSTRACT

Biodegradable Poly(L-lactic acid) microspheres containing neutron-activable ¹⁶⁵Ho were designed for internal radiation therapy of hepatic tumors. Spheres composed of Poly(L-lactic acid) (PLA) were prepared with excellent reproducibility containing up to 36% of a holmium complex. The prepared spheres were irradiated in a high neutron flux converting ¹⁶⁵Hoto to ¹⁶⁶Ho (Emax = 1.84 MeV, half-life = 26.9 hr). Thus, these microspheres can be prepared under conditions that do not require the handling of a hazardous radionuclide, and then irradiated just prior to administration. In vitro studies in plasma (n = 6) revealed 97.3% (± 1.9) retention of ¹⁶⁶Ho in the microspheres after 240 hr. PLA spheres administered via the portal vein in rabbits (n = 6) show 94.5% (± 3.4) retention of the original ¹⁶⁶Ho activity in the liver after 6 days.

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