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[ 18 F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • الموضوع:
    • نبذة مختصرة :
      The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways-such as those induced by irradiation. Here, we used a third-generation PARP1-specific radiotracer, [ 18 F]-PARPZ, to delineate castrate resistant prostate cancer xenografts. Following treatment with the clinically applied [ 225 Ac]-PSMA-617, positron emission tomography was performed and correlative autoradiography and histology acquired. [ 18 F]-PARPZ was able to distinguish treated from control (saline) xenografts by increased uptake. Kinetic analysis of tracer accumulation also suggests that the localization of the agent to sites of increased PARP-1 expression is a consequence of DNA damage response. Together, these data support expanded investigation of [ 18 F]-PARPZ to facilitate clinical translation in the ⍺-therapy space.
      (© 2022. The Author(s).)
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    • Grant Information:
      R01 CA201035 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; P30 CA091842 United States CA NCI NIH HHS; R01 CA229893 United States CA NCI NIH HHS; R01 EB029752 United States EB NIBIB NIH HHS
    • الرقم المعرف:
      0 (Fluorine Radioisotopes)
      0 (Poly(ADP-ribose) Polymerase Inhibitors)
    • الموضوع:
      Date Created: 20220729 Date Completed: 20220802 Latest Revision: 20240516
    • الموضوع:
      20240516
    • الرقم المعرف:
      PMC9338249
    • الرقم المعرف:
      10.1038/s41598-022-17460-0
    • الرقم المعرف:
      35906379