研究动态
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STING 靶向 PET 示踪剂,用于结直肠癌化疗后肿瘤免疫原性的早期评估。

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

发表日期:2023 Nov 04
作者: Duo Xu, Xin Lu, Fan Yang, Zebo Jiang, Shirui Yang, Lei Bi, Jiani Liu, Hong Shan, Dan Li
来源: Eur J Nucl Med Mol I

摘要:

为了优化化疗方案,提高化疗联合免疫治疗的疗效,采用特异性靶向干扰素基因刺激剂(STING)的PET示踪剂[18F]FBTA,监测结直肠癌化疗后肿瘤免疫原性的早期变化。 CRC)小鼠。甲苯磺酸盐前体被 18F 标记,产生 STING 靶向探针 -[18F]FBTA。使用奥沙利铂(OXA)或顺铂(CDDP)治疗的CRC小鼠进行[18F]FBTA-PET成像和生物分布。还用低剂量(CDDP-LD:1毫克/千克)或中剂量(CDDP-MD:2.5毫克/千克)CDDP治疗CRC小鼠,并进行PET成像和生物分布。通过流式细胞术和免疫组化验证不同化疗药物和不同剂量CDDP对肿瘤先天免疫的影响。CRC小鼠PET成像显示OXA治疗化疗早期肿瘤摄取显着增强(3.09±0.25%ID/ g) 和 CDDP (4.01±0.18%ID/g),特别是在 CDDP 组中。 PET 衍生的肿瘤摄取值与 STING 免疫组织化学评分具有很强的相关性。流式细胞术显示这两种药物都能导致树突状细胞和巨噬细胞浸润到肿瘤中。与 OXA 相比,CDDP 治疗在 CRC 肿瘤中招募更多的 DC 和巨噬细胞。 CDDP-LD 和 CDDP-MD 治疗均提高了 CRC 肿瘤的摄取,尤其是 CDDP-MD 组。免疫组织化学和流式细胞术证实CDDP-MD治疗比CDDP-LD治疗招募更多的DC和巨噬细胞。总体而言,STING靶向示踪剂-[18F]FBTA被证明可以监测CRC小鼠化疗后肿瘤免疫原性的早期变化。此外,STING靶向策略可能有助于选择合适的化疗方案,包括化疗药物和剂量,从而进一步改善CRC化疗后联合免疫治疗的临床决策。© 2023。作者,获得Springer独家许可-Verlag GmbH 德国,施普林格自然集团的一部分。
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.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.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.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.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.