PURPOSE: Despite the clinical evidence of actinium-225 (Ac)-based targeted alpha therapies (TαT) efficacy, optimized treatment regimens are needed to improve overall clinical response rates and decrease toxicities. The nuclear recoil effect of Ac and its resulting daughter nuclides have been hypothesized to contribute to non-targeted damage. However, a lack of generator concepts for radionuclidically pure francium-221 (Fr), involvement of strong acids for elution, and its short half-life (4.8 min), has limited in vivo studies. Here, we report on a successful application of an Ac/Fr generator concept and the in vivo distribution of Fr and bismuth-213 (Bi). METHODS: The immobilization of Ac and elution of Fr was performed on a LN2 resin column. The biodistribution of Fr and Bi was investigated in male SCID mice with LNCaP tumors at 5 and 15 min p.i. RESULTS: Our results indicate that LN2 resin is a highly efficient resin for selective separation of Ac and Fr. The use of 0.1 M NaOAc enabled continuous elution at a constant pH. The biodistribution study revealed a fast distribution of Fr and Bi already 5 min p.i. We observed a strong accumulation of Fr to the kidneys, salivary glands and small intestine. In Bi-injected mice, the highest accumulation was in kidney and liver. CONCLUSION: We present an unprecedented concept utilizing LN2 resin in Ac/Fr generator applications. Successfully eluted and injected Fr fractions showed strong accumulation of Fr and Bi in key organs. Our data provide preliminary evidence of the potential contribution of recoiled progeny radionuclides to side-effects in non-targeted organs.