2025/07/01 by Sabine Zitzmann-Kolbe, Yvonne Remde, Ingrid Moen +9 · 1 voice
Medicine · #Radiopharmaceutical Chemistry and Applications #Lung Cancer Treatments and Mutations #Medical Imaging Techniques and Applications
paper · pdf · doi:10.1007/s00259-025-07427-4
openalex publication_date 2025/07/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
Abstract Purpose Despite the clinical evidence of actinium-225 ( 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 225 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 ( 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 225 Ac/ 221 Fr generator concept and the in vivo distribution of 221 Fr and bismuth-213 ( 213 Bi). Methods The immobilization of 225 Ac and elution of 221 Fr was performed on a LN2 resin column. The biodistribution of 221 Fr and 213 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 225 Ac and 221 Fr. The use of 0.1 M NaOAc enabled continuous elution at a constant pH. The biodistribution study revealed a fast distribution of 221 Fr and 213 Bi already 5 min p.i. We observed a strong accumulation of 221 Fr to the kidneys, salivary glands and small intestine. In 213 Bi-injected mice, the highest accumulation was in kidney and liver. Conclusion We present an unprecedented concept utilizing LN2 resin in 225 Ac/ 221 Fr generator applications. Successfully eluted and injected 221 Fr fractions showed strong accumulation of 221 Fr and 213 Bi in key organs. Our data provide preliminary evidence of the potential contribution of recoiled progeny radionuclides to side-effects in non-targeted organs.