Journal Article DKFZ-2025-01404

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Biodistribution of free Francium-221 and Bismuth-213 in Tumour-bearing SCID mice after successful development of Actinium-225/Francium-221 radionuclide generator Set-up.

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2025
Springer-Verl. Heidelberg [u.a.]

European journal of nuclear medicine and molecular imaging nn, nn () [10.1007/s00259-025-07427-4]
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Abstract: Despite the clinical evidence of actinium-225 (225Ac)-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 225Ac 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 (221Fr), 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 225Ac/221Fr generator concept and the in vivo distribution of 221Fr and bismuth-213 (213Bi).The immobilization of 225Ac and elution of 221Fr was performed on a LN2 resin column. The biodistribution of 221Fr and 213Bi was investigated in male SCID mice with LNCaP tumors at 5 and 15 min p.i.Our results indicate that LN2 resin is a highly efficient resin for selective separation of 225Ac and 221Fr. The use of 0.1 M NaOAc enabled continuous elution at a constant pH. The biodistribution study revealed a fast distribution of 221Fr and 213Bi already 5 min p.i. We observed a strong accumulation of 221Fr to the kidneys, salivary glands and small intestine. In 213Bi-injected mice, the highest accumulation was in kidney and liver.We present an unprecedented concept utilizing LN2 resin in 225Ac/221Fr generator applications. Successfully eluted and injected 221Fr fractions showed strong accumulation of 221Fr and 213Bi in key organs. Our data provide preliminary evidence of the potential contribution of recoiled progeny radionuclides to side-effects in non-targeted organs.

Keyword(s): Actinium-225 ; Bismuth-213 ; Francium-221 ; Radionuclide generators ; Radionuclide-specific organ accumulation ; Targeted alpha therapies

Classification:

Note: #LA:E270# / epub

Contributing Institute(s):
  1. Radiopharmazeutika und Präklinische Studien (W630)
  2. Translationale Radiotheranostik (E270)
Research Program(s):
  1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2025
Database coverage:
Medline ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2025-07-17, last modified 2025-07-20



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