Chromium-51 (51Cr) is an attractive radionuclide for diagnosis, which is usually applied for red cells and platelet radiolabeling. However, commercially available 51Cr produced in nuclear reactors via neutron activation requires long irradiation times and complex separation methods. In this work, five metal–organic frameworks (MIL-100 (Cr), MIL-100 (Fe), MIL-100 (Al), MIL-101 (Cr) and aluminium fumarate MOF (FuAl)) were synthesized and the effect of gamma ray irradiation with a high dose rate and a maximum dose of 6 MGy was investigated. The two chromium-based MOFs, MIL-100 (Cr) and MIL-101 (Cr), were selected as radiation targets to produce high specific activity 51Cr by the Szilard-Chalmers effect. A solid–liquid extraction was applied to extract the produced 51Cr under different conditions, including different extractants, extraction times and pH. The most promising results were achieved when using irradiated MIL-101 (Cr) and EDTA as extracting agent, reaching an enrichment factor of 1132 ± 50.