Abstract
In this thesis, preclinical studies on new treatment modalities for ovarian cancer are descibed, applying radiolabeled antibodies and radiolabeled RGD-peptides. In chapter 2 a study is described comparing the therapeutic efficacy of the antibody HMFG1 radiolabeled with several beta-emitting radionuclides in mice with intraperitoneal ovarian carcinoma. Mice were injected with the radiopharmaceuticals 90Y-HMFG1, 186Re-HMFG1 or 131I-HMFG1. Each of the i.p. administered radiolabeled antibody preparations caused a significant delay in tumor growth when compared to the control groups. No preference for either radiolabel was observed. In chapter 3, initial biodistribution and therapy studies of the dimeric RGD-peptide DOTA-E-[c(RGDfK)]2 in an ovarian cancer xenograft model are described. At the maximal tolerated dose, a single i.v. injection of 90Y-DOTA-E-[c(RGDfK)]2 caused a significant growth delay of the ovarian cancer xenografts when compared to therapy with the 90Y-labeled scrambled peptide. In chapter 4 a dosimetric analysis of 90Y-DOTA-E-[c(RGKfD)]2 is described. As beta-radiation cannot be visualized properly after injection, a substitute for 90Y should be used. It was concluded that in future dosimetric studies, analysis of the images after injection of the 111In-labeled peptide allows adequate estimation of the radiation doses to the relevant tissues. In chapter 5 the tumor targeting characteristics of a monomeric and a dimeric RGD-peptide are described. The dimer showed a significantly higher tumor uptake, but also a higher kidney retention. Tumor-to-kidney ratios were in favour of the monomer which is important since high kidney retention is unfavourable for future therapy. In chapter 6 the effect of dose fractionation on tumor targeting with a RGD-peptide was investigated. This approach did not result in differences in therapeutic effect between the fractionated and the non-fractionated therapy. In chapter 7, the results and conclusions of the studies that have been described in this thesis are discussed
