STING-targeted PET tracer for early assessment of tumor immunogenicity in colorectal cancer after chemotherapy.

Purpose: To optimize chemotherapy regimens and improve the effectiveness of chemotherapy combined with immunotherapy, a PET tracer specifically targeting the stimulator of interferon genes (STING), denoted as [18F]FBTA was used to monitor the early changes in tumor immunogenicity after chemotherapy...

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Published in:European Journal of Nuclear Medicine & Molecular Imaging Vol. 51; no. 3; pp. 641 - 656
Main Authors: Xu, Duo, Lu, Xin, Yang, Fan, Jiang, Zebo, Yang, Shirui, Bi, Lei, Liu, Jiani, Shan, Hong, Li, Dan
Format: Journal Article
Published: Springer Nature Feb2024
Online Access:View this record in EBSCOhost
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      dt: Feb2024
      vid: 51
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      pub: Springer Nature
      place: New York, New York
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        173394471
        10.1007/s00259-023-06485-w
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        atl: STING-targeted PET tracer for early assessment of tumor immunogenicity in colorectal cancer after chemotherapy.
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        au:
          Xu, Duo
          Lu, Xin
          Yang, Fan
          Jiang, Zebo
          Yang, Shirui
          Bi, Lei
          Liu, Jiani
          Shan, Hong
          Li, Dan
        affil: https://ror.org/0064kty71 Department of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-Sen University, 519000, Zhuhai, China
      sug:
      ab: Purpose: To optimize chemotherapy regimens and improve the effectiveness of chemotherapy combined with immunotherapy, a PET tracer specifically targeting the stimulator of interferon genes (STING), denoted as [18F]FBTA was used to monitor the early changes in tumor immunogenicity after chemotherapy in colorectal cancer (CRC) mice. Methods: The toluene sulfonate precursor was labeled with 18F to produce the STING targeted probe—[18F]FBTA. [18F]FBTA-PET imaging and biodistribution were performed using CRC mice treated with oxaliplatin (OXA) or cisplatin (CDDP). CRC mice were also treated with low (CDDP-LD: 1 mg/kg) or medium (CDDP-MD: 2.5 mg/kg) doses of CDDP, and subjected to PET imaging and biodistribution. The effects of different chemotherapeutic agents and different doses of CDDP on tumor innate immunity were verified by flow cytometry and immunohistochemistry. Results: PET imaging of CRC mice exhibited notably enhanced tumor uptake in the early phase of chemotherapy with treatment with OXA (3.09 ± 0.25%ID/g) and CDDP (4.01 ± 0.18%ID/g), especially in the CDDP group. The PET-derived tumor uptake values have strong correlations with STING immunohistochemical score. Flow cytometry showed both agents led to DCs and macrophages infiltration in tumors. Compared with OXA, CDDP treatment recruits more DCs and macrophages in CRC tumors. Both CDDP-LD and CDDP-MD treatment elevated uptake in CRC tumors, especially in CDDP-MD group. Immunohistochemistry and flow cytometry confirmed CDDP-MD treatment recruits more DCs and macrophages than CDDP-LD treatment. Conclusion: Overall, the STING-targeted tracer—[18F]FBTA was demonstrated to monitor early changes in tumor immunogenicity in CRC mice after chemotherapy. Besides, the STING-targeted strategy may help to select the appropriate chemotherapy regimen, including chemotherapeutic agents and doses, which further improve clinical decision making for combination immunotherapy after chemotherapy for CRC.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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