Outline of the subsequent chapters

1.7 Outline of the subsequent chapters

In Chapter 2 the preparation and neutron activation of holmium containing poly(Llactic
acid) microspheres is presented. The microspheres were prepared using a
solvent evaporation technique and the effect of the formulation and processing
parameters on the holmium loading were evaluated. Further, the effects of neutron
irradiation conditions were examined and defined in detail. In Chapter 3 the crystal
structures of two holmium acetylacetonate complexes were elucidated using X-ray
diffraction. Chapter 4 describes an in depth characterization of PLLA microspheres
loaded with HoAcAc. PLLA microspheres, and as a control PLLA films, with and
without HoAcAc were investigated using a variety of advanced techniques. Chapter
5 deals with the influence of neutron irradiation on the HoAcAc loaded PLLA
microspheres. Possible radiation damage of both the PLLA matrix and the Hocomplex
was investigated. In Chapter 6 the biodistribution of PLLA microspheres
loaded with 166Ho is studied in rats with liver tumours. The distribution of the activity,
especially the tumour-to-normal liver-tissue ratio, after administration of 166Ho-PLLA
microspheres with sizes between 20 and 50 μm was determined. Also, an extensive
histological evaluation was performed. Chapter 7 reports on the therapeutic effect of
166Ho-PLLA microspheres in a rabbit model. Liver function was examined by
histology and analysis of liver enzyme activity. Chapter 8 summarises this thesis and
gives suggestions for further research to enable clinical application of Ho-loaded
PLLA microspheres for the internal radionuclide therapy of tumours.