In the proposed study, the insulin-like growth factor I (IGF-I) should be introduced into diagnostic cancer research
using receptor scintigraphy for tumor and metastatic spread localization. The effects of IGF-I are mediated by
binding to cell surface membrane-expressed receptors. The over-expression of IGF-I receptors in human tumors
may provide the molecular basis for the localization diagnosis of honor sites using radiolabeled IGF-I. The peptides
will be radiolabeled with 123L 99mTc and 67/68Ga for future SPECT/PET studies, respectively. In vitro studies
will focus on the evaluation of labeling with different isotopes and the determination of the qualitative and
quantitative distribution of receptor binding sites in normal and tumor cell lines as well as in normal and tumor
tissues. Moreover, competition with similar structured peptides (IGF-1L insulin,...) using different radioligand
binding methods will be examined. Additionally, smaller IGF-I analogs should be synthesized, whereas receptor
subtypes should be transfected in Cos cells. Ligand-receptor complexes will be determined using Northern Blotting
and SDS-PAGE. Furthermore, functional studies (measurement of thymidine-uptake and phosphorylation after
addition of IGF-I) will be practiced. Based on these data, the suitability of labeled IGF-I for in vivo use in cancer
padents (localization and visualization of tumors using receptor scintigraphy and PET) will be evaluated.