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@ARTICLE{Widjaja:305612,
      author       = {L. Widjaja and J. Hornfeck and S. C. Siegmund and F. J.
                      Gildehaus and N.-S. Schmidt-Hegemann and V. Wenter and G. T.
                      Sheikh and K. Klimek and J. Casuscelli and C. G. Stief and
                      M. J. Zacherl and R. A. Werner$^*$},
      title        = {{R}efining the clinical utility of
                      [177{L}u]{L}u/[225{A}c]{A}c-{PSMA} tandem {RLT} in patients
                      with metastatic castration resistant prostate cancer.},
      journal      = {European journal of nuclear medicine and molecular imaging},
      volume       = {nn},
      issn         = {1619-7070},
      address      = {Heidelberg [u.a.]},
      publisher    = {Springer-Verl.},
      reportid     = {DKFZ-2025-02262},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {This study aimed to evaluate the efficacy and safety of
                      Lutetium-177/Actinium-225 prostate-specific membrane antigen
                      tandem radioligand therapy ([177Lu]Lu/[225Ac]Ac-PSMA tandem
                      RLT) and to explore clinical and imaging-based predictors of
                      treatment response to support individualized patient
                      selection.This retrospective, single-center study included
                      23 patients with mCRPC who underwent Fluor-18
                      ([18F]F)-PSMA-1007 positron emission tomography/computed
                      tomography (PET/CT) and subsequent tandem RLT. Whole-body
                      tumor segmentation on PET/CT and standard laboratory values
                      were acquired before treatment initiation. Primary endpoint
                      was partial response (PR), defined as either a decline in
                      prostate specific antigen of ≥ $50\%$ (according to
                      prostate cancer clinical trial working group) or PET-based
                      response according to Response Evaluation Criteria on PSMA
                      PET/CT. Safety assessment included renal and hematological
                      side effects following common terminology criteria of
                      adverse events version 5.Following two cycles of tandem RLT,
                      11 patients $(48\%)$ achieved a PR. The treatment was
                      generally tolerated well. Grade 3 events included renal
                      impairment in two $(9\%)$ and grade 3 anemia in five
                      $(22\%)$ patients, while no Grade 4/5 events occurred.
                      Patients with increased PSMA expression on pretherapeutic
                      PET (defined by the average mean standardized uptake value
                      of all tumor lesions [SUVmean]) had a higher response rate
                      $(86\%;$ 6 out of 7) compared to those with decreased
                      SUVmean $(31\%;$ 5 out of 16). In Cox regression analysis,
                      SUVmean was significantly associated with PR with a hazard
                      ratio of 1.34 $(95\%$ CI, 1.01-1.77; P = 0.042). PSMA-tumor
                      volume (P = 0.036) and total lesion-PSMA (P = 0.041) were
                      also significant predictors, whereas none of the clinical
                      parameters showed predictive value. Kaplan-Meier analysis
                      further confirmed SUVmean as the strongest PR (P =
                      0.003).[177Lu]Lu/[225Ac]Ac-PSMA tandem RLT may offer a safe,
                      effective treatment option. Assessment of PSMA expression on
                      pretherapeutic PET predicts response, supporting its use in
                      guiding personalized treatment.},
      keywords     = {PSMA-RLT (Other) / Prostate cancer (Other) / Tandem RLT
                      (Other) / Targeted alpha therapy (Other)},
      cin          = {MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41174098},
      doi          = {10.1007/s00259-025-07632-1},
      url          = {https://inrepo02.dkfz.de/record/305612},
}