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Background  Tracers triggering αvβ3 integrins, such as certain RGD-containing peptides, were found promising in previous pilot studies characterizing high-grade gliomas. However, only limited comparisons have been performed with current PET tracers. This study aimed at comparing the biodistribution of  18 F-fluorodeoxyglucose ( 18 F-FDG) with that of  68 Ga-NODAGA-RGD, an easily synthesized monomeric RGD compound with rapid kinetics, in two different rodent models of engrafted human glioblastoma.    Methods  Nude rodents bearing human U87-MG glioblastoma tumor xenografts in the flank (34 tumors in mice) or in the brain (5 tumors in rats) were analyzed. Kinetics of  68 Ga-NODAGA-RGD and of  18 F-FDG were compared with PET imaging in the same animals, along with additional autohistoradiographic analyses and blocking tests for  68 Ga-NODAGA-RGD.    Results  Both tracers showed a primary renal route of clearance, although with faster clearance for  68 Ga-NODAGA-RGD resulting in higher activities in the kidneys and bladder. The tumor activity from  68 Ga-NODAGA-RGD, likely corresponding to true integrin binding (i.e., suppressed by co-injection of a saturating excess of unlabeled RGD), was found relatively high, but only at the 2 nd  hour following injection, corresponding on average to 53% of total tumor activity. Tumor uptake of  68 Ga-NODAGA-RGD decreased progressively with time, contrary to that of  18 F-FDG, although  68 Ga-NODAGA-RGD exhibited 3.4 and 3.7-fold higher tumor-to-normal brain ratios on average compared to  18 F-FDG in mice and rat models, respectively. Finally, ex-vivo analyses revealed that the tumor areas with high  68 Ga-NODAGA-RGD uptake also exhibited the highest rates of cell proliferation and αv integrin expression, irrespective of cell density.    Conclusions   68 Ga-NODAGA-RGD has a high potential for PET imaging of glioblastomas, especially for areas with high integrin expression and cell proliferation, although PET recording needs to be delayed until the 2 nd  hour following injection in order to provide sufficiently high integrin specificity.    Electronic supplementary material  The online version of this article (10.1186/s13550-018-0405-5) contains supplementary material, which is available to authorized users.

PET imaging of 68Ga-NODAGA-RGD, as compared with 18F-fluorodeoxyglucose, in experimental rodent models of engrafted glioblastoma