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In-beam positron emission tomography (in-beam PET) is a valuable in situ method for quality assurance in radiation therapy. It is well investigated for therapy with carbon ions and has been successfully implemented clinically at the Gesellschaft for Schwerionenforschung (GSI), Darmstadt, Germany. The extension of this efficient technique to other radiation treatment modalities may be worthwhile. For protons, 3He, 7Li, and 16O the feasibility has already been experimentally shown. Furthermore, it seems to be feasible for the case of radiotherapy with high-energy photons, since positron emitters are generated by photons with energies above ~ 20 MeV due to (gamma,n) photo-nuclear reactions (predominantly 11C and 15O in tissue). In this regard, promising conclusions have been obtained by Geant4 simulations as well as by off-beam PET experiments using a conventional PET scanner. The next step was the installation of a small double head positron camera consisting of two bismuth germanate (BGO) block detectors at the irradiation site to measure the generated beta+ activity distribution simultaneously to the irradiation. The relation between deposited dose and beta+ activity density was quantified. The obtained results are presented and compared to that of off-beam PET experiments. Higher activities as well as an improved contrast between materials of different stoichiometry are achieved by measuring in-beam, showing the advantage of in-beam PET over off-beam PET. Thus, the application of in-beam PET to radiation therapy with high-energy photons can be useful for quality assurance, comprising monitoring of dose delivery, patient positioning and tumor response.