Radiolabeled receptor binding peptides have emerged as an important class of tracers for tumor diagnosis. The specific receptor binding property of the ligand can be exploited by labeling the ligand with a radionuclide and using the radiolabeled ligand as a vehicle to guide the radioactivity to the tissues expressing a particular receptor. For peptide receptor radionuclide imaging peptides are labeled mainly with gamma emitting radionuclides In-111 and Tc-99m. To exploit the exquisite sensitivity and resolution of PET imaging the peptide could be labeled with positron emitting radionuclides such as Ga-68, F-18 and Cu-64. F-18 is the most widely used radionuclide in PET: it has ideal nuclear characteristics and is widely available. Recently, we developed a new one-step chelate-based F-18 labeling method that can be used to label peptides and other small molecules with high efficiency (Laverman et al., J Nucl Med 2010;51:454-461). This new labeling method is based on the chelation of aluminumfluoride (“AlF-18”) by NOTA. In ongoing projects we aim to optimize and further exploit this new one-step chelate-based F-18 labeling method. Focus will be on various F-18 labeled peptides (somatostatin and bombesin analogues and RGDfK) for PET imaging of neuroendocrine tumors, prostate cancer and for αvβ3 expression in tumors, respectively. Peptides will be conjugated with an optimized NOTA analogue. The effect of various linkers will be tested to further optimize the pharmacokinetic properties of the peptides. In the second part of the project, the clinical feasibility of the new F-18 labeling method will be demonstrated using one of the F-18-labeled peptides in patients.