Fibroblast Activation Protein Targeting Probe with Gly-Pro Sequence for PET of Glioblastoma
文献类型：期刊论文
| 作者 | Lai, Chaoquan1,2; Cao, Rui2; Li, Renda2; He, Chunfeng2; Wang, Xiao4; Shi, Hui2; Qu, Chunrong2; Qian, Kun2; Song, Shaoli4; Chen, Wen-Hua1 |
| 刊名 | MOLECULAR PHARMACEUTICS
 |
| 出版日期 | 2023-07-24 |
| 卷号 | 20期号:8页码:4120-4128 |
| 关键词 | glioblastoma fibroblast activation protein FAPI PET imaging |
| ISSN号 | 1543-8384 |
| DOI | 10.1021/acs.molpharmaceut.3c00248 |
| 通讯作者 | Song, Shaoli(shaoli-song@163.com) ; Chen, Wen-Hua(whchen@wyu.edu.cn) ; Cheng, Zhen(zcheng@simm.ac.cn) |
| 英文摘要 | As an important cancer-associated fibroblast-specificbiomarker,fibroblast activation protein (FAP) has become an attractive targetfor tumor diagnosis and treatment. However, most FAP-based radiotracersshowed inadequate uptake and short retention in tumors. In this study,we designed and synthesized a novel FAP ligand (DOTA-GPFAPI-04) throughassembling three functional moieties: a quinoline-based FAP inhibitorfor specifically targeting FAP, a FAP substrate Gly-Pro asa linker for increasing the FAP protein interaction, and a 2,2 & PRIME;,2 & DPRIME;,2"'-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraaceticacid (DOTA) chelator for radiolabeling with different radionuclides.The FAP targeting ability of DOTA-GPFAPI-04 was investigated by moleculardocking studies. DOTA-GPFAPI-04 was then radiolabeled with Ga-68 to give [Ga-68]Ga-DOTA-GPFAPI-04 for positron emissiontomography (PET) imaging of glioblastoma. [Ga-68]Ga-DOTA-GPFAPI-04exhibited a purity of >98% and high stability analyzed by radio-HPLCin saline and mouse serum. Cell uptake studies demonstrated the targetingspecificity of the probe. Further in vivo pharmacokineticstudies in normal mice demonstrated the quick clearance of the probe.Moreover, compared with the widely studied [Ga-68]Ga-FAPI-04,[Ga-68]Ga-DOTA-GPFAPI-04 showed much higher U87MG tumoruptake values (4.467 & PLUSMN; 0.379 for [Ga-68]Ga-DOTA-GPFAPI-04and 1.267 & PLUSMN; 0.208% ID/g for [Ga-68]Ga-FAPI-04 at 0.5h post-injection, respectively). The area under the curve based ontime-activity curve (TAC) analysis for tumor radioactivityin small animal models was 422.5 for [Ga-68]Ga-DOTA-GPFAPI-04and 98.14 for [Ga-68]Ga-FAPI-04, respectively, demonstratingthat the former had longer tumor retention time. The tumor-to-muscle(T/M) ratio for [Ga-68]Ga-DOTA-GPFAPI-04 reached 9.15 ina U87MG xenograft animal model. PET imaging and blocking assays showedthat [Ga-68]Ga-DOTA-GPFAPI-04 had specific tumor uptake.In summary, this study demonstrates the successful synthesis and evaluationof a novel FAPI targeting probe, [Ga-68]Ga-DOTA-GPFAPI-04,with a Gly-Pro sequence. It shows favorable in vivo glioblastoma imaging properties and relatively long tumor retention,highlighting DOTA-GPFAPI-04 as a promising molecular scaffold fordeveloping FAP targeting tumor theranostic agents. |
| WOS关键词 | SPECIFICITY ; ARTHRITIS |
| 资助项目 | Shanghai Municipal Science and Technology Major Project[TM202301H003] ; National Natural Science Foundation of China[U2267221] ; National Natural Science Foundation of China[81901799] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001034978600001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306851]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Song, Shaoli; Chen, Wen-Hua; Cheng, Zhen |
| 作者单位 | 1.Wuyi Univ, Sch Biotechnol & Hlth Sci, Jiangmen 529020, Guangdong, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China 4.Fudan Univ, Dept Nucl Med, Shanghai Canc Ctr, Shanghai 200032, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lai, Chaoquan,Cao, Rui,Li, Renda,et al. Fibroblast Activation Protein Targeting Probe with Gly-Pro Sequence for PET of Glioblastoma[J]. MOLECULAR PHARMACEUTICS,2023,20(8):4120-4128. |
| APA | Lai, Chaoquan.,Cao, Rui.,Li, Renda.,He, Chunfeng.,Wang, Xiao.,...&Cheng, Zhen.(2023).Fibroblast Activation Protein Targeting Probe with Gly-Pro Sequence for PET of Glioblastoma.MOLECULAR PHARMACEUTICS,20(8),4120-4128. |
| MLA | Lai, Chaoquan,et al."Fibroblast Activation Protein Targeting Probe with Gly-Pro Sequence for PET of Glioblastoma".MOLECULAR PHARMACEUTICS 20.8(2023):4120-4128. |
入库方式： OAI收割
来源：上海药物研究所
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