577 - Ultra-High Specific Activity Microspheres for Transarterial Radioembolization (TARE)

Purpose: The objective of this work was to assess the post-activation stability of a new class of TARE microspheres that use holmium-166 (Ho-166) as the therapeutic radionuclide.

Materials and Methods: Aluminosilicate-holmium oxide glass microspheres (ID SS02, 0.9956 g, MoSci LLC, Rolla MO) were weighed into a quartz tube (8 mm x 6 cm), capped, and sealed into an aluminum capsule. The capsule was placed in a neutron flux in the McMaster Nuclear Reactor (Hamilton, Canada) for neutron bombardment (t = 48 h). The capsule was decay-stored underwater (t = 13 d) prior to quantification of the Ho-166 in a dose calibrator (Atomlab 500, Biodex).
The microspheres were suspended in phosphate buffered saline (3.000 mL); leaching of trace metals was monitored for 25 d by gamma spectroscopy (ORTEC HPGe detector, Gamma Vision & Aptec MCA software) and ICP-OES (Agilent 5800 VDV).
The radionuclides in the microspheres were quantified by gamma spectroscopy using a NIST-traceable calibration curve. Optical images were acquired with a Zeiss microscope fitted with a digital camera (Axiocam, ZEN software); Scanning Electron Microscopy images were acquired with a FEI Versa Dual Beam Scattering Electron Microscope instrument.

Results: The microspheres attained an End of Bombardment (EoB) activity of 2.57 TBq/g Ho-166. Assuming a delay-to-administration period of 72 h to permit processing, QC, and transportation, this would enable clinical delivery of microspheres at 400 GBq/g – a significantly higher specific activity than currently available TARE devices.

No substantial damage to the microspheres was detected either by chemical testing or microscopy, which showed smooth, spherical particles with no evidence of cracking or breaking indicating the spheres are highly radiation resistant.

The radionuclidic purity of the Ho-166 was excellent ( > 99.99% at EoB + 72 h) despite the presence of eight minor radioactive impurities. The Ho-166 was the only major contributor to the lifetime dose imparted by the device ( >99.88 % of total dose), which surpasses the recommended value of >95% {1}.

Conclusion: These results suggest that aluminosilicate-holmium oxide glasses are a viable class of materials for TARE microspheres. The specific activity achieved was limited by the neutron flux available: activation to >10 TBq/g can theoretically be achieved in a higher-power facility. Future work will focus on optimizing the chemical composition of the glass microspheres, assaying the biocompatibility of the glasses, and developing clinically representative imaging protocols to assess the possibility of CBCT-guided dosimetry.