W. Bult, H. de Leeuw, O.M. Steinebach, M.J. van der Bom, H.Th. Wolterbeek, R.M.A. Heeren, C.J.G. Bakker, A.D. van het Schip, W.E. Hennink & J.F.W. Nijsen
PURPOSE: The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted.
METHODS: HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS.
RESULTS: After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days.
CONCLUSION: HoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment.