SPECT Imaging with Tc-99m-Labeled HYNIC-FAPI-04 to Extend the Differential Time Window in Evaluating Tumor Fibrosis

作者全名："Luo, Xiu; Zhang, Zhe; Cheng, Chao; Wang, Tao; Fang, Danzhou; Zuo, Changjing; Yuan, Gengbiao; Li, Rou; Li, Xiao"

作者地址："[Luo, Xiu; Cheng, Chao; Wang, Tao; Zuo, Changjing; Li, Rou; Li, Xiao] Shanghai Changhai Hosp, Dept Nucl Med, Shanghai 200433, Peoples R China; [Zhang, Zhe; Fang, Danzhou; Yuan, Gengbiao] Chongqing Med Univ, Dept Nucl Med, Affiliated Hosp 2, Chongqing 400010, Peoples R China"

通信作者："Li, R (通讯作者)，Shanghai Changhai Hosp, Dept Nucl Med, Shanghai 200433, Peoples R China.; Yuan, GB (通讯作者)，Chongqing Med Univ, Dept Nucl Med, Affiliated Hosp 2, Chongqing 400010, Peoples R China."

来源：PHARMACEUTICALS

ESI学科分类：　

WOS号：WOS:000959584600001

JCR分区：Q1

影响因子：4.3

年份：2023

卷号：16

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：Tc-99m-HYNIC-FAPI-04; differential time window; tumor fibrosis; fibroblast activating protein; FAP inhibitor; FAPI-04

摘要："The so-far used Ga-68- or F-18-labelled tracers are of a relative short time window in differentiating tumor fibrosis. SPECT applicable imaging probe, Tc-99m-HYNIC-FAPI-04, was synthesized and evaluated in tumor cells and animal models of FAP-positive glioma and FAP-negative hepatoma, and then compared with F-18-FDG or Ga-68-FAPI-04 PET/CT. The radio-labeling rate of Tc-99m-HYNIC-FAPI-04 was greater than 90%, and the radiochemical purity was >99% after purification with sep-pak C18 column. In vitro cell uptake experiments of Tc-99m-HYNIC-FAPI-04 showed good FAP binding specificity, and the cellular uptake significantly decreased when blocked by DOTA-FAPI-04, reflecting the similar targeting mechanism of HYNIC-FAPI-04 and DOTA-FAPI-04. SPECT/CT imaging showed that U87MG tumor was distinguishable and of a high uptake of Tc-99m-HYNIC-FAPI-04 (2.67 +/- 0.35 %ID/mL at 1.5 h post injection (h P.I.), while tumor signal of FAP-negative HUH-7 was as low as 0.34 +/- 0.06 %ID/mL. At 5 h P.I., U87MG tumor was still distinguishable (1.81 +/- 0.20 %ID/mL). In comparison, although U87MG tumor was of obvious Ga-68-FAPI-04 uptake and clearly visible at 1 h P.I., the tumorous radioactive signals were fuzzy at 1.5 h P.I. Tc-99m-HYNIC-FAPI-04 specifically bound to FAP-positive tumors and qualified with the ability of evaluating tumor fibrosis over longer time windows."

基金机构："Special Foundation for Emerging Interdisciplinary Field Research of Shanghai Municipal Health Commission [2022JC004]; National Natural Science Foundation of China [82272040]; First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital) ""Guhai Plan in the 14th Five-Year Plan period"" [GH145-22]; ""Discipline Construction Climbing 234 Plan"" of Shanghai Changhai Hospital of Naval Medical University [2019YPT002, 2020YPT002]"

基金资助正文："This research was funded by the Special Foundation for Emerging Interdisciplinary Field Research of Shanghai Municipal Health Commission (Grant No. 2022JC004), the National Natural Science Foundation of China (Grant No. 82272040), the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital) ""Guhai Plan in the 14th Five-Year Plan period"" (Grant No. GH145-22), and the ""Discipline Construction Climbing 234 Plan"" of Shanghai Changhai Hospital of Naval Medical University (Grant No. 2019YPT002 and 2020YPT002)."