Abstract
The expression of integrin /spl alpha//sub v//spl beta//sub 3/ on sprouting capillary cells and their interaction with specific extracellular matrix ligands play a key role in tumor angiogenesis and metastasis. In several malignancies, tumor expression of integrin /spl alpha//sub v//spl beta//sub 3/ correlates well with tumor progression. Non-invasive imaging methods to visualize and quantify integrin /spl alpha//sub v//spl beta//sub 3/ expression in vivo are crucial for the success of anti-angiogenic therapy targeting integrin. Suitably labeled RGD peptides (potent integrin /spl alpha//sub v//spl beta//sub 3/ antagonists) and antibodies have been developed for PET, SPECT and NIR fluorescence imaging of small animals. Due to the high sensitivity and adequate spatial and temporal resolution of PET, development of PET probes for integrin expression imaging has been the mainstay of active research. We improved the tumor targeting efficacy and in vivo pharmacokinetics by applying polyvalency effect and designed /sup 18/F- and /sup 64/Cu-labeled dimeric and multimeric RGD peptides for both imaging and imaging-guided internal radiotherapy applications.
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