Extended Structure–Activity Relationship and Pharmacokinetic Investigation of (4-Quinolinoyl)glycyl-2-cyanopyrrolidine Inhibitors of Fibroblast Activation Protein (FAP)Click to copy article linkArticle link copied!
- Koen Jansen
- Leen Heirbaut
- Robert Verkerk
- Jonathan D. Cheng
- Jurgen Joossens
- Paul Cos
- Louis Maes
- Anne-Marie Lambeir
- Ingrid De Meester
- Koen Augustyns
- Pieter Van der Veken
Abstract

Fibroblast activation protein (FAP) is a serine protease related to dipeptidyl peptidase IV (DPPIV). It has been convincingly linked to multiple disease states involving remodeling of the extracellular matrix. FAP inhibition is investigated as a therapeutic option for several of these diseases, with most attention so far devoted to oncology applications. We previously discovered the N-4-quinolinoyl-Gly-(2S)-cyanoPro scaffold as a possible entry to highly potent and selective FAP inhibitors. In the present study, we explore in detail the structure–activity relationship around this core scaffold. We report extensively optimized compounds that display low nanomolar inhibitory potency and high selectivity against the related dipeptidyl peptidases (DPPs) DPPIV, DPP9, DPPII, and prolyl oligopeptidase (PREP). The log D values, plasma stabilities, and microsomal stabilities of selected compounds were found to be highly satisfactory. Pharmacokinetic evaluation in mice of selected inhibitors demonstrated high oral bioavailability, plasma half-life, and the potential to selectively and completely inhibit FAP in vivo.
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- Xuran Zhang, Kyo Chul Lee, Joon Young Choi, Kyung-Han Lee, Yearn Seong Choe. Comparative Study of Dimeric Fibroblast Activation Protein-Targeting Radioligands Labeled with Fluorine-18, Copper-64, and Gallium-68. Molecular Pharmaceutics 2025, 22
(2)
, 906-917. https://doi.org/10.1021/acs.molpharmaceut.4c01080
- Zuojie Li, Qing Ruan, Yuhao Jiang, Qianna Wang, Guangxing Yin, Junhong Feng, Junbo Zhang. Current Status and Perspectives of Novel Radiopharmaceuticals with Heterologous Dual-targeted Functions: 2013–2023. Journal of Medicinal Chemistry 2024, 67
(24)
, 21644-21670. https://doi.org/10.1021/acs.jmedchem.4c01608
- Vladimir Kubyshkin, Pavel K. Mykhailiuk. Proline Analogues in Drug Design: Current Trends and Future Prospects. Journal of Medicinal Chemistry 2024, 67
(22)
, 20022-20055. https://doi.org/10.1021/acs.jmedchem.4c01987
- Andrea Galbiati, Matilde Bocci, Silvia Gervasoni, Eleonora Prodi, Giuliano Malloci, Dario Neri, Samuele Cazzamalli. Molecular Evolution of Multivalent OncoFAP Derivatives with Enhanced Tumor Uptake and Prolonged Tumor Retention. Journal of Medicinal Chemistry 2024, 67
(15)
, 13392-13408. https://doi.org/10.1021/acs.jmedchem.4c01295
- Spencer D. Lindeman, Owen C. Booth, Pooja Tudi, Taylor C. Schleinkofer, Jackson N. Moss, Nicholas B. Kearney, Ramesh Mukkamala, Lauren K. Thompson, Mollie A. Modany, Madduri Srinivasarao, Philip S. Low. FAP Radioligand Linker Optimization Improves Tumor Dose and Tumor-to-Healthy Organ Ratios in 4T1 Syngeneic Model. Journal of Medicinal Chemistry 2024, 67
(14)
, 11827-11840. https://doi.org/10.1021/acs.jmedchem.4c00448
- Dominik Polterauer, Simon Wagschal, Michael Bersier, Clara Bovino, Dominique M. Roberge, Christopher A. Hone, C. Oliver Kappe. Deoxyfluorination of Ketones with Sulfur Tetrafluoride (SF4) and Dialkylamines in Continuous Flow Mode. Organic Process Research & Development 2024, 28
(7)
, 2919-2927. https://doi.org/10.1021/acs.oprd.4c00180
- Muhammet Tanc, Nicolò Filippi, Yentl Van Rymenant, Sergei Grintsevich, Isabel Pintelon, Marlies Verschuuren, Joni De Loose, Emile Verhulst, Euy Sung Moon, Lorenzo Cianni, Sigrid Stroobants, Koen Augustyns, Frank Roesch, Ingrid De Meester, Filipe Elvas, Pieter Van der Veken. Druglike, 18F-labeled PET Tracers Targeting Fibroblast Activation Protein. Journal of Medicinal Chemistry 2024, 67
(9)
, 7068-7087. https://doi.org/10.1021/acs.jmedchem.3c02402
- Feize Li, Huan Ma, Hao Luo, Guohua Shen, Jing Su, Huawei Cai, Xijian Chen, Tu Lan, Yuanyou Yang, Jiali Liao, Ning Liu. 211At-Labeled Nanoscale Polydopamine Decorated with FAPI for Synergistic Targeted-Alpha Therapy and Photothermal Therapy of Glioma. ACS Applied Nano Materials 2024, 7
(7)
, 6831-6838. https://doi.org/10.1021/acsanm.3c05525
- Stephen W. Wright, Kathleen A. Farley, Seungil Han, John D. Knafels, Katherine L. Lee. In Retrospect: Root-Cause Analysis of Structure–Activity Relationships in IRAK4 Inhibitor Zimlovisertib (PF-06650833). ACS Medicinal Chemistry Letters 2024, 15
(4)
, 540-545. https://doi.org/10.1021/acsmedchemlett.4c00036
- Xinyue Du, Bingxin Gu, Xiao Wang, Xiangwei Wang, Mengjing Ji, Jianping Zhang, Simin He, Xiaoping Xu, Zhongyi Yang, Shaoli Song. Preclinical Evaluation and a Pilot Clinical Positron Emission Tomography Imaging Study of [68Ga]Ga-FAPI-FUSCC-II. Molecular Pharmaceutics 2024, 21
(2)
, 904-915. https://doi.org/10.1021/acs.molpharmaceut.3c01008
- Runwei Jiao, Xuhong Ren, Xiheng Li, Shitao Sun, Hao Zhu, Bin Lin, Huiming Hua, Dahong Li, Xinhua He. Divergent Synthesis of Quinolines: Exploiting the Duality of Free Radicals. Organic Letters 2024, 26
(1)
, 51-56. https://doi.org/10.1021/acs.orglett.3c03490
- Xuran Zhang, Joon Young Choi, Kyung-Han Lee, Yearn Seong Choe. Synthesis and Evaluation of [18F]SiFA-Conjugated Ligands for Fibroblast Activation Protein Imaging. Molecular Pharmaceutics 2023, 20
(12)
, 6441-6450. https://doi.org/10.1021/acs.molpharmaceut.3c00824
- Ziyue Yu, Yong Huang, Hualong Chen, Zeng Jiang, Chengze Li, Yi Xie, Zhongjing Li, Xuebo Cheng, Yajing Liu, Shengli Li, Ying Liang, Zehui Wu. Design, Synthesis, and Evaluation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein for Brain Imaging. ACS Pharmacology & Translational Science 2023, 6
(11)
, 1745-1757. https://doi.org/10.1021/acsptsci.3c00187
- Chaoquan Lai, Rui Cao, Renda Li, Chunfeng He, Xiao Wang, Hui Shi, Chunrong Qu, Kun Qian, Shaoli Song, Wen-Hua Chen, Zhen Cheng. Fibroblast Activation Protein Targeting Probe with Gly–Pro Sequence for PET of Glioblastoma. Molecular Pharmaceutics 2023, 20
(8)
, 4120-4128. https://doi.org/10.1021/acs.molpharmaceut.3c00248
- Yinwen Wang, Hongmei Yuan, Nan Liu, Sufan Tang, Yue Feng, Yang Liu, Ping Cai, Li Xia, Wenlu Zheng, Yue Chen, Zhijun Zhou. High Affinity and FAP-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake for FAP Inhibitors. Journal of Medicinal Chemistry 2023, 66
(13)
, 8614-8627. https://doi.org/10.1021/acs.jmedchem.3c00259
- Haiyan Hong, Zhihao Zha, Ruiyue Zhao, Yang Luo, Wenbin Jin, Linlin Li, Ran Wang, Li Yan, Hui Wang, Karl Ploessl, Jinping Qiao, Lin Zhu, Hank F. Kung. [68Ga]Ga-HBED-CC-FAPI Derivatives with Improved Radiolabeling and Specific Tumor Uptake. Molecular Pharmaceutics 2023, 20
(4)
, 2159-2169. https://doi.org/10.1021/acs.molpharmaceut.2c01112
- Pengxin Qiao, Yutong Wang, Ke Zhu, Danzha Zheng, Yangmeihui Song, Dawei Jiang, Chunxia Qin, Xiaoli Lan. Noninvasive Monitoring of Reparative Fibrosis after Myocardial Infarction in Rats Using 68Ga-FAPI-04 PET/CT. Molecular Pharmaceutics 2022, 19
(11)
, 4171-4178. https://doi.org/10.1021/acs.molpharmaceut.2c00551
- Liang Zhao, Jianhao Chen, Yizhen Pang, Jianyang Fang, Kaili Fu, Lingxin Meng, Xianzhong Zhang, Zhide Guo, Hua Wu, Long Sun, Guoqiang Su, Qin Lin, Haojun Chen. Development of Fibroblast Activation Protein Inhibitor-Based Dimeric Radiotracers with Improved Tumor Retention and Antitumor Efficacy. Molecular Pharmaceutics 2022, 19
(10)
, 3640-3651. https://doi.org/10.1021/acs.molpharmaceut.2c00424
- Pavel K. Mykhailiuk. Fluorine-Containing Prolines: Synthetic Strategies, Applications, and Opportunities. The Journal of Organic Chemistry 2022, 87
(11)
, 6961-7005. https://doi.org/10.1021/acs.joc.1c02956
- Qing Ruan, Junhong Feng, Yuhao Jiang, Xuran Zhang, Xiaojiang Duan, Qianna Wang, Guangxing Yin, Di Xiao, Junbo Zhang. Preparation and Bioevaluation of 99mTc-Labeled FAP Inhibitors as Tumor Radiotracers to Target the Fibroblast Activation Protein. Molecular Pharmaceutics 2022, 19
(1)
, 160-171. https://doi.org/10.1021/acs.molpharmaceut.1c00712
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(11)
, 4179-4187. https://doi.org/10.1021/acs.molpharmaceut.1c00566
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(19)
, 14028-14045. https://doi.org/10.1021/acs.jmedchem.1c01010
- Jia-Jia Lin, Chia-Pao Chuang, Jia-Yu Lin, Feng-Ting Huang, Chiun-Wei Huang. Rational Design, Pharmacomodulation, and Synthesis of [68Ga]Ga-Alb-FAPtp-01, a Selective Tumor-Associated Fibroblast Activation Protein Tracer for PET Imaging of Glioma. ACS Sensors 2021, 6
(9)
, 3424-3435. https://doi.org/10.1021/acssensors.1c01316
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(7)
, 1223-1231. https://doi.org/10.1021/acs.bioconjchem.1c00305
- Anchen Fu, Hongbo Wang, Taotao Huo, Xinwei Li, Wei Fu, Rongqin Huang, Zhijuan Cao. A Novel Chemiluminescence Probe for Sensitive Detection of Fibroblast Activation Protein-Alpha In Vitro and in Living Systems. Analytical Chemistry 2021, 93
(16)
, 6501-6507. https://doi.org/10.1021/acs.analchem.1c00413
- Stephanie L. Slania, Deepankar Das, Ala Lisok, Yong Du, Zirui Jiang, Ronnie C. Mease, Steven P. Rowe, Sridhar Nimmagadda, Xing Yang, Martin G. Pomper. Imaging of Fibroblast Activation Protein in Cancer Xenografts Using Novel (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine-Based Small Molecules. Journal of Medicinal Chemistry 2021, 64
(7)
, 4059-4070. https://doi.org/10.1021/acs.jmedchem.0c02171
- Yibo Zhou, Keyi Yin, Hao Dong, Sheng Yang, JunBin Li, Jinqiu Luo, Yi Li, Ronghua Yang. Long-Lasting Bioluminescence Imaging of the Fibroblast Activation Protein by an Amphiphilic Block Copolymer-Based Probe. Analytical Chemistry 2021, 93
(8)
, 3726-3732. https://doi.org/10.1021/acs.analchem.0c03638
- Yuxing Lin, Zhao Ma, Zhenzhen Li, Yuqi Gao, Xiaojun Qin, Zheng Zhang, Guankai Wang, Lupei Du, Minyong Li. Bioluminescent Probe for Monitoring Endogenous Fibroblast Activation Protein-Alpha. Analytical Chemistry 2019, 91
(23)
, 14873-14878. https://doi.org/10.1021/acs.analchem.9b02117
- Jessica Plescia, Stéphane De Cesco, Mihai Burai Patrascu, Jerry Kurian, Justin Di Trani, Caroline Dufresne, Alexander S. Wahba, Naëla Janmamode, Anthony K. Mittermaier, Nicolas Moitessier. Integrated Synthetic, Biophysical, and Computational Investigations of Covalent Inhibitors of Prolyl Oligopeptidase and Fibroblast Activation Protein α. Journal of Medicinal Chemistry 2019, 62
(17)
, 7874-7884. https://doi.org/10.1021/acs.jmedchem.9b00642
- An De Decker, Gwendolyn Vliegen, Dries Van Rompaey, Anke Peeraer, An Bracke, Line Verckist, Koen Jansen, Ruth Geiss-Friedlander, Koen Augustyns, Hans De Winter, Ingrid De Meester, Anne-Marie Lambeir, Pieter Van der Veken. Novel Small Molecule-Derived, Highly Selective Substrates for Fibroblast Activation Protein (FAP). ACS Medicinal Chemistry Letters 2019, 10
(8)
, 1173-1179. https://doi.org/10.1021/acsmedchemlett.9b00191
- Nicholas A. Meanwell. Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design. Journal of Medicinal Chemistry 2018, 61
(14)
, 5822-5880. https://doi.org/10.1021/acs.jmedchem.7b01788
- Andrea Testa, Xavier Lucas, Guilherme V. Castro, Kwok-Ho Chan, Jane E. Wright, Andrew C. Runcie, Morgan S. Gadd, William T. A. Harrison, Eun-Jung Ko, Daniel Fletcher, Alessio Ciulli. 3-Fluoro-4-hydroxyprolines: Synthesis, Conformational Analysis, and Stereoselective Recognition by the VHL E3 Ubiquitin Ligase for Targeted Protein Degradation. Journal of the American Chemical Society 2018, 140
(29)
, 9299-9313. https://doi.org/10.1021/jacs.8b05807
- Petra Dvořáková, Petr Bušek, Tomáš Knedlík, Jiří Schimer, Tomáš Etrych, Libor Kostka, Lucie Stollinová Šromová, Vladimír Šubr, Pavel Šácha, Aleksi Šedo, and Jan Konvalinka . Inhibitor-Decorated Polymer Conjugates Targeting Fibroblast Activation Protein. Journal of Medicinal Chemistry 2017, 60
(20)
, 8385-8393. https://doi.org/10.1021/acs.jmedchem.7b00767
- Naoki Okugawa, Katsuhiko Moriyama, and Hideo Togo . Introduction of Quinolines and Isoquinolines onto Nonactivated α-C–H Bond of Tertiary Amides through a Radical Pathway. The Journal of Organic Chemistry 2017, 82
(1)
, 170-178. https://doi.org/10.1021/acs.joc.6b02303
- Chong Si, Kevin R. Fales, Alicia Torrado, Kwame Frimpong, Talbi Kaoudi, Harold George Vandeveer, and F. George Njoroge . Enantioselective Synthesis of 3,3-Difluoropyrrolidin-4-ol, a Valuable Building Block in Medicinal Chemistry. The Journal of Organic Chemistry 2016, 81
(10)
, 4359-4363. https://doi.org/10.1021/acs.joc.6b00305
- Sam Hofmans, Tom Vanden Berghe, Lars Devisscher, Behrouz Hassannia, Sophie Lyssens, Jurgen Joossens, Pieter Van Der Veken, Peter Vandenabeele, and Koen Augustyns . Novel Ferroptosis Inhibitors with Improved Potency and ADME Properties. Journal of Medicinal Chemistry 2016, 59
(5)
, 2041-2053. https://doi.org/10.1021/acs.jmedchem.5b01641
- Eric P. Gillis, Kyle J. Eastman, Matthew D. Hill, David J. Donnelly, and Nicholas A. Meanwell . Applications of Fluorine in Medicinal Chemistry. Journal of Medicinal Chemistry 2015, 58
(21)
, 8315-8359. https://doi.org/10.1021/acs.jmedchem.5b00258
- Ricardo Köchel, Stefan Wagner, Katrin Schwegmann, Michael Schäfers, Hans-Jörg Breyholz, Bernhard Wünsch. Synthesis of piperazine-based fluorinated fibroblast activation protein inhibitors for the development of a novel 18F-labeled PET imaging probe. European Journal of Medicinal Chemistry 2025, 290 , 117513. https://doi.org/10.1016/j.ejmech.2025.117513
- Lei Wang, Chao-Cheng Chen, Devon Chapple, Antonio A. W. L. Wong, Sara Kurkowska, Wing Sum Lau, Carlos F. Uribe, François Bénard, Kuo-Shyan Lin. Synthesis and Evaluation of 68Ga- and 177Lu-Labeled [diF-Pro14]Bombesin(6−14) Analogs for Detection and Radioligand Therapy of Gastrin-Releasing Peptide Receptor-Expressing Cancer. Pharmaceuticals 2025, 18
(2)
, 234. https://doi.org/10.3390/ph18020234
- Qingyu Zhang, Zhoumi Hu, Haitao Zhao, Fuqiang Du, Chun Lv, Tukang Peng, Yukai Zhang, Bowu Zhang, Jianjun Liu, Cheng Wang. Design, Synthesis, and Biological Evaluation of a Novel [18F]AlF-H3RESCA-FAPI Radiotracer Targeting Fibroblast Activation Protein. Pharmaceuticals 2025, 18
(2)
, 277. https://doi.org/10.3390/ph18020277
- Xinyan Qiu, Qianqian Gan, Tianxiong Ji, Hongchuang Xu, Kai Cui, Long Yi, Xing Yang, Min-Fu Yang. Rational modifications on N-(4-quinolinoyl)-Gly-2-cyanopyrrolidine to develop fibroblast activation protein-targeted radioligands with improved affinity and tumor uptake. European Journal of Medicinal Chemistry 2025, 281 , 117011. https://doi.org/10.1016/j.ejmech.2024.117011
- Huiya Zhang, Yuyu Xing, Yixuan Yang, Bixi Tang, Zhaoyun Zong, Jia Li, Yi Zang, Matthew Bogyo, Xiaojie Lu, Shiyu Chen. DNA‐Encoded Noncanonical Substrate Library for Protease Profiling. ChemBioChem 2024, 25
(23)
https://doi.org/10.1002/cbic.202400559
- Yuriko Mori, Emil Novruzov, Dominik Schmitt, Jens Cardinale, Tadashi Watabe, Peter L. Choyke, Abass Alavi, Uwe Haberkorn, Frederik L. Giesel. Clinical applications of fibroblast activation protein inhibitor positron emission tomography (FAPI-PET). npj Imaging 2024, 2
(1)
https://doi.org/10.1038/s44303-024-00053-z
- Juliette Fouillet, Jade Torchio, Léa Rubira, Cyril Fersing. Unveiling the Tumor Microenvironment Through Fibroblast Activation Protein Targeting in Diagnostic Nuclear Medicine: A Didactic Review on Biological Rationales and Key Imaging Agents. Biology 2024, 13
(12)
, 967. https://doi.org/10.3390/biology13120967
- Mingsong Shi, Fang Wang, Zhou Lu, Yuan Yin, Xueting Zheng, Decai Wang, Xianfu Cai, Meng Jing, Jianjun Wang, Junxian Chen, Xile Jiang, Wenliang Yu, Xiaoan Li. Elucidating the linagliptin and fibroblast activation protein binding mechanism through molecular dynamics and binding free energy analysis. iScience 2024, 27
(12)
, 111368. https://doi.org/10.1016/j.isci.2024.111368
- Radhika Narain, Ian Nessler, Paul L. Richardson, Jamie E. Erickson, Yuzhen Wang, Jacqueline Ferri, Heather L. Knight, Shaughn H. Bryant, Lucy A. Phillips, Liang Zhang, Soumya Mitra. Increased imaging ligand hydrophilicity and improved pharmacokinetic properties provides enhanced in vivo targeting of fibroblast activation protein. npj Imaging 2024, 2
(1)
https://doi.org/10.1038/s44303-024-00028-0
- Qingyu Zhang, Zhoumi Hu, Haitao Zhao, Fuqiang Du, Chun Lv, Tukang Peng, Yukai Zhang, Bowu Zhang, Jianjun Liu, Cheng Wang. Design, Synthesis and Biological Evaluation of a Novel [18F]AlF-H3RESCA-FAPI Radiotracer Targeting Fibroblast Activation Protein.. 2024https://doi.org/10.21203/rs.3.rs-5297123/v1
- Léa Rubira, Jade Torchio, Juliette Fouillet, Johanne Vanney, Cyril Fersing. GMP-Compliant Automated Radiolabeling and Quality Controls of [68Ga]Ga-FAPI-46 for Fibroblast Activation Protein-Targeted PET Imaging in Clinical Settings. Chemical and Pharmaceutical Bulletin 2024, 72
(11)
, 1014-1023. https://doi.org/10.1248/cpb.c24-00531
- Kentaro Hisada, Kazuko Kaneda-Nakashima, Yoshifumi Shirakami, Yuichiro Kadonaga, Atsuko Saito, Tadashi Watabe, Sifan Feng, Kazuhiro Ooe, Xiaojie Yin, Hiromitsu Haba, Masashi Murakami, Atsushi Toyoshima, Jens Cardinale, Frederik L. Giesel, Koichi Fukase. Comparison Length of Linker in Compound for Nuclear Medicine Targeting Fibroblast Activation Protein as Molecular Target. International Journal of Molecular Sciences 2024, 25
(22)
, 12296. https://doi.org/10.3390/ijms252212296
- Mahshid Kiani, Safura Jokar, Leila Hassanzadeh, Hossein Behnammanesh, Omid Bavi, Davood Beiki, Majid Assadi. Recent Clinical Implications of FAPI. Clinical Nuclear Medicine 2024, 49
(11)
, e538-e556. https://doi.org/10.1097/RLU.0000000000005348
- Ziyue Yu, Zeng Jiang, Xuebo Cheng, Leilei Yuan, Hualong Chen, Lin Ai, Zehui Wu. Development of fibroblast activation protein-α radiopharmaceuticals: Recent advances and perspectives. European Journal of Medicinal Chemistry 2024, 277 , 116787. https://doi.org/10.1016/j.ejmech.2024.116787
- Uwe Haberkorn, Annette Altmann, Frederik L. Giesel, Clemens Kratochwil. 1,090 Publications and 5 Years Later: Is FAP-Targeted Theranostics Really Happening?. Journal of Nuclear Medicine 2024, 65
(10)
, 1518-1520. https://doi.org/10.2967/jnumed.124.267923
- Martha Sahylí Ortega Pijeira, Paulo Sérgio Gonçalves Nunes, Samila Leon Chaviano, Aida M. Abreu Diaz, Jean N. DaSilva, Eduardo Ricci-Junior, Luciana Magalhães Rebelo Alencar, Xiaoyuan Chen, Ralph Santos-Oliveira. Medicinal (Radio) Chemistry: Building Radiopharmaceuticals for the
Future. Current Medicinal Chemistry 2024, 31
(34)
, 5481-5534. https://doi.org/10.2174/0929867331666230818092634
- Yongyi Chen, Jiacheng Du, Xiangchuan Meng, Ling-Ling Wu, Qingyang Zhang, Xiaowan Han, Leilei Zhang, Qinghua Wang, Hai-Yu Hu. A self-immobilizing near-infrared fluorogenic probe for in vivo imaging of fibroblast activation protein-α. Talanta 2024, 278 , 126475. https://doi.org/10.1016/j.talanta.2024.126475
- Yaxin Tian, Yanghongyan Jiang, Ping Ma, Xiaowei Ma, Liang Du, Fengkui Wang, Xiaodong Yu, Qian Zhao. Radiosynthesis and in-vitro identification of a molecular probe 131I-FAPI targeting cancer-associated fibroblasts. Frontiers in Oncology 2024, 14 https://doi.org/10.3389/fonc.2024.1442601
- Bo-Jun Ke, Saeed Abdurahiman, Francesca Biscu, Gaia Zanella, Gabriele Dragoni, Sneha Santhosh, Veronica De Simone, Anissa Zouzaf, Lies van Baarle, Michelle Stakenborg, Veronika Bosáková, Yentl Van Rymenant, Emile Verhulst, Sare Verstockt, Elliott Klein, Gabriele Bislenghi, Albert Wolthuis, Jan Frič, Christine Breynaert, Andre D’Hoore, Pieter Van der Veken, Ingrid De Meester, Sara Lovisa, Lukas J.A.C. Hawinkels, Bram Verstockt, Gert De Hertogh, Séverine Vermeire, Gianluca Matteoli. Intercellular interaction between FAP+ fibroblasts and CD150+ inflammatory monocytes mediates fibrostenosis in Crohn’s disease. Journal of Clinical Investigation 2024, 134
(16)
https://doi.org/10.1172/JCI173835
- Yuxiang Shang, Guojin Zhang, Xinchao Yao, Chaoquan Lai, Fanghu Wang, Baozhen Zeng, Entao Liu, Hui Yuan, Zhen Cheng, Lei Jiang. [68Ga]Ga-labeled FAPI Conjugated with Gly-Pro Sequence for PET Imaging of Malignant Tumors. Molecular Imaging and Biology 2024, 26
(4)
, 729-737. https://doi.org/10.1007/s11307-024-01935-9
- Ramesh Mukkamala, Daniel J. Carlson, Nicholas Kaine Miller, Spencer D. Lindeman, Emily Renee Bowen, Pooja Tudi, Taylor Schleinkofer, Owen C. Booth, Abigail Cox, Madduri Srinivasarao, Philip S. Low. Design of a Fibroblast Activation Protein–Targeted Radiopharmaceutical Therapy with High Tumor–to–Healthy-Tissue Ratios. Journal of Nuclear Medicine 2024, 65
(8)
, 1257-1263. https://doi.org/10.2967/jnumed.124.267756
- Tianxiong Ji, Chunfang Zan, Lina Li, Jianbo Cao, Yao Su, Hongliang Wang, Zhifang Wu, Min-Fu Yang, Kefei Dou, Sijin Li. Molecular Imaging of Fibroblast Activation in Rabbit Atherosclerotic Plaques: a Preclinical PET/CT Study. Molecular Imaging and Biology 2024, 26
(4)
, 680-692. https://doi.org/10.1007/s11307-024-01919-9
- Tilman Läppchen, Adrianna Bilinska, Eirinaios Pilatis, Elena Menéndez, Surachet Imlimthan, Euy Sung Moon, Ali Afshar-Oromieh, Frank Rösch, Axel Rominger, Eleni Gourni. Tailoring Fibroblast-Activation Protein Targeting for Theranostics: A Comparative Preclinical Evaluation of the 68Ga- and 177Lu-Labeled Monomeric and Dimeric Fibroblast-Activation Protein Inhibitors DOTA.SA.FAPi and DOTAGA.(SA.FAPi)2. Molecules 2024, 29
(13)
, 3093. https://doi.org/10.3390/molecules29133093
- Richard P. Baum, Emil Novruzov, Tianzhi Zhao, Lukas Greifenstein, Vivianne Jakobsson, Elisabetta Perrone, Aditi Mishra, Aleksandr Eismant, Kriti Ghai, Ortwin Klein, Bastian Jaeschke, Daniel Benz-Zils, Jens Cardinale, Yuriko Mori, Frederik L. Giesel, Jingjing Zhang. Radiomolecular Theranostics With Fibroblast-Activation-Protein Inhibitors and Peptides. Seminars in Nuclear Medicine 2024, 54
(4)
, 537-556. https://doi.org/10.1053/j.semnuclmed.2024.05.010
- Joseph Ford, Sebastiano Ortalli, Véronique Gouverneur. The
18
F‐Difluoromethyl Group: Challenges, Impact and Outlook. Angewandte Chemie 2024, 136
(26)
https://doi.org/10.1002/ange.202404957
- Joseph Ford, Sebastiano Ortalli, Véronique Gouverneur. The
18
F‐Difluoromethyl Group: Challenges, Impact and Outlook. Angewandte Chemie International Edition 2024, 63
(26)
https://doi.org/10.1002/anie.202404957
- Habibollah Dadgar, Nasim Norouzbeigi, Esmail Jafari, Batool Al-balooshi, Akram Al-Ibraheem, Mohamad Haidar, Yehia Omar, Abdulredha A. Esmail, Fahad Marafi, Sharjeel Usmani, Andrea Cimini, Hossein Arabi, Majid Assadi. Exploring the efficacy of FAPI PET/CT in the diagnosis and treatment management of colorectal cancer: a comprehensive literature review and initial experience. Clinical and Translational Imaging 2024, 12
(3)
, 235-252. https://doi.org/10.1007/s40336-023-00609-w
- Xi-Yang Cui, Zhu Li, Ziren Kong, Yu Liu, Hao Meng, Zihao Wen, Changlun Wang, Junyi Chen, Mengxin Xu, Yiyan Li, Jingyue Gao, Wenjia Zhu, Zhixin Hao, Li Huo, Shaoyan Liu, Zhi Yang, Zhibo Liu. Covalent targeted radioligands potentiate radionuclide therapy. Nature 2024, 73 https://doi.org/10.1038/s41586-024-07461-6
- Navin Sakhare, Arpit Mitra, Avik Chakraborty, Sudeep Sahu, Laxman Ram, Sutapa Rakshit, Sanjeev Kumar, Anupam Mathur, Usha Pandey. Radiochemical synthesis and pre-clinical evaluation of [68Ga]Ga-FAPI-4 formulated using in-house developed FAPI-4 kit. Journal of Radioanalytical and Nuclear Chemistry 2024, 10 https://doi.org/10.1007/s10967-024-09476-9
- Morten Bentestuen, Surenth Nalliah, Marie M.K. Stolberg, Helle D. Zacho. How to Perform FAPI PET? An Expedited Systematic Review Providing a Recommendation for FAPI PET Imaging With Different FAPI Tracers. Seminars in Nuclear Medicine 2024, 54
(3)
, 345-355. https://doi.org/10.1053/j.semnuclmed.2023.11.003
- Jiang Su, Julianna Desmarais, Cong-Qiu Chu, Jing Zhu. Potential therapeutic targets of fibrosis in inflammatory rheumatic diseases. Best Practice & Research Clinical Rheumatology 2024, 38
(2)
, 101945. https://doi.org/10.1016/j.berh.2024.101945
- Marcin Skorenski, Shanping Ji, Steven H. L. Verhelst. Covalent activity-based probes for imaging of serine proteases. Biochemical Society Transactions 2024, 52
(2)
, 923-935. https://doi.org/10.1042/BST20231450
- Dan Wu, Xuesu Zhou, Jiaqi Zhang, Fengfeng Xue, Lexuan Ding, Lu An, Qiwei Tian. A FAPI-conjugated FITC fluorescence probe for targeted cancer imaging. New Journal of Chemistry 2024, 48
(14)
, 6314-6321. https://doi.org/10.1039/D3NJ05934K
- Léa Rubira, Charlotte Donzé, Juliette Fouillet, Benjamin Algudo, Pierre Olivier Kotzki, Emmanuel Deshayes, Cyril Fersing. [68Ga]Ga-FAPI-46 synthesis on a GAIA® module system: Thorough study of the automated radiolabeling reaction conditions. Applied Radiation and Isotopes 2024, 206 , 111211. https://doi.org/10.1016/j.apradiso.2024.111211
- Simon Rauber, Hashem Mohammadian, Christian Schmidkonz, Armin Atzinger, Alina Soare, Christoph Treutlein, Samuel Kemble, Christopher B. Mahony, Manuel Geisthoff, Mario R. Angeli, Maria G. Raimondo, Cong Xu, Kai-Ting Yang, Le Lu, Hannah Labinsky, Mina S. A. Saad, Charles A. Gwellem, Jiyang Chang, Kaiyue Huang, Eleni Kampylafka, Johannes Knitza, Rostyslav Bilyy, Jörg H. W. Distler, Megan M. Hanlon, Ursula Fearon, Douglas J. Veale, Frank W. Roemer, Tobias Bäuerle, Hans M. Maric, Simone Maschauer, Arif B. Ekici, Christopher D. Buckley, Adam P. Croft, Torsten Kuwert, Olaf Prante, Juan D. Cañete, Georg Schett, Andreas Ramming. CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis. Nature Immunology 2024, 25
(4)
, 682-692. https://doi.org/10.1038/s41590-024-01774-4
- Xiaona Sun, Yuxuan Wu, Xingkai Wang, Xin Gao, Siqi Zhang, Zhicheng Sun, Ruping Liu, Kuan Hu. Beyond Small Molecules: Antibodies and Peptides for Fibroblast Activation Protein Targeting Radiopharmaceuticals. Pharmaceutics 2024, 16
(3)
, 345. https://doi.org/10.3390/pharmaceutics16030345
- Shreya Bendre, Helen Merkens, Hsiou-Ting Kuo, Pauline Ng, Antonio A.W.L. Wong, Wing Sum Lau, Zhengxing Zhang, Sara Kurkowska, Chao-Cheng Chen, Carlos Uribe, François Bénard, Kuo-Shyan Lin. Development, preclinical evaluation and preliminary dosimetry profiling of SB03178, a first-of-its-kind benzo[h]quinoline-based fibroblast activation protein-α-targeted radiotheranostic for cancer imaging and therapy. European Journal of Medicinal Chemistry 2024, 268 , 116238. https://doi.org/10.1016/j.ejmech.2024.116238
- Madhav P. Yadav, Sanjana Ballal, Marcel Martin, Frank Roesch, Swayamjeet Satapathy, Euy S. Moon, Madhavi Tripathi, Ajay Gogia, Chandrasekhar Bal. Therapeutic potential of [177Lu]Lu-DOTAGA-FAPi dimers in metastatic breast cancer patients with limited treatment options: efficacy and safety assessment. European Journal of Nuclear Medicine and Molecular Imaging 2024, 51
(3)
, 805-819. https://doi.org/10.1007/s00259-023-06482-z
- S. V. Ryabukhin, D. V. Bondarenko, S. A. Trofymchuk, D. A. Lega, D. M. Volochnyuk. Aza‐Heterocyclic Building Blocks with In‐Ring CF
2
‐Fragment. The Chemical Record 2024, 24
(2)
https://doi.org/10.1002/tcr.202300283
- Arsyangela Verena, Helen Merkens, Chao-Cheng Chen, Devon E. Chapple, Lei Wang, Shreya Bendre, Antonio A. W. L. Wong, François Bénard, Kuo-Shyan Lin. Synthesis and Preclinical Evaluation of Two Novel 68Ga-Labeled Bispecific PSMA/FAP-Targeted Tracers with 2-Nal-Containing PSMA-Targeted Pharmacophore and Pyridine-Based FAP-Targeted Pharmacophore. Molecules 2024, 29
(4)
, 800. https://doi.org/10.3390/molecules29040800
- Shuo Liu, QianYang Chen, Lili Wang, MeiChen Tong, HaiBo Sun, Ming Dong, WeiDong Niu, LiNa Wang. The novel protein complex FAPα/ITGA5 is involved in the bone destruction of apical periodontitis. International Journal of Biological Macromolecules 2024, 259 , 128200. https://doi.org/10.1016/j.ijbiomac.2023.128200
- John Gehris, Charlie Ervin, Charlotte Hawkins, Sydney Womack, Amelia M. Churillo, Jonathan Doyle, Albert J. Sinusas, Francis G. Spinale. Fibroblast activation protein: Pivoting cancer/chemotherapeutic insight towards heart failure. Biochemical Pharmacology 2024, 219 , 115914. https://doi.org/10.1016/j.bcp.2023.115914
- Sarah E. Poplawski, Robin M. Hallett, Mark H. Dornan, Kyle E. Novakowski, Shuang Pan, Anthony P. Belanger, Quang-De Nguyen, Wengen Wu, Albert E. Felten, Yuxin Liu, Shin Hye Ahn, Valerie S. Hergott, Barry Jones, Jack H. Lai, Joe A.B. McCann, William W. Bachovchin. Preclinical Development of PNT6555, a Boronic Acid–Based, Fibroblast Activation Protein-α (FAP)–Targeted Radiotheranostic for Imaging and Treatment of FAP-Positive Tumors. Journal of Nuclear Medicine 2024, 65
(1)
, 100-108. https://doi.org/10.2967/jnumed.123.266345
- Frank Rösch, Markus Piel, Janine Ackermann. Radiochemie/Tracer. 2024, 35-63. https://doi.org/10.1007/978-3-662-67192-4_4
- Christian B.M. Poulie, Vladimir Shalgunov, Filipe Elvas, Yentl Van Rymenant, Euy-Sung Moon, Umberto Maria Battisti, Joni De Loose, Ingrid De Meester, Frank Rösch, Pieter Van Der Veken, Matthias M. Herth. Next generation fibroblast activation protein (FAP) targeting PET tracers - The tetrazine ligation allows an easy and convenient way to 18F-labeled (4-quinolinoyl)glycyl-2-cyanopyrrolidines. European Journal of Medicinal Chemistry 2023, 262 , 115862. https://doi.org/10.1016/j.ejmech.2023.115862
- Ayça Arçay Öztürk, Patrick Flamen. FAP-targeted PET imaging in gastrointestinal malignancies: a comprehensive review. Cancer Imaging 2023, 23
(1)
https://doi.org/10.1186/s40644-023-00598-z
- Sanjana Ballal, Madhav P. Yadav, Frank Roesch, Swayamjeet Satapathy, Euy Sung Moon, Marcel Martin, Nicky Wakade, Parvind Sheokand, Madhavi Tripathi, Kunal R. Chandekar, Shipra Agarwal, Ranjit Kumar Sahoo, Sameer Rastogi, Chandrasekhar Bal. Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers. European Journal of Nuclear Medicine and Molecular Imaging 2023, 51
(1)
, 233-244. https://doi.org/10.1007/s00259-023-06404-z
- Austin Craig, Jürgen Kogler, Markus Laube, Martin Ullrich, Cornelius K. Donat, Robert Wodtke, Klaus Kopka, Sven Stadlbauer. Preparation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein via Sulfur [18F]Fluoride Exchange Reaction. Pharmaceutics 2023, 15
(12)
, 2749. https://doi.org/10.3390/pharmaceutics15122749
- Lilan Fu, Jiawen Huang, Qingxing Liu, Fei Xie, Yanjiang Han, Penghui Sun, Min Cao, Yanchao Huang, Kongzhen Hu, Ganghua Tang. Radiosynthesis, preclinical evaluation and pilot clinical PET imaging study of a 18F-labeled tracer targeting fibroblast activation protein. Bioorganic Chemistry 2023, 141 , 106878. https://doi.org/10.1016/j.bioorg.2023.106878
- Kuo-Ting Chen. Novel Imaging Probes: From Design to Applications. Pharmaceuticals 2023, 16
(10)
, 1506. https://doi.org/10.3390/ph16101506
- Kun Liu, Min Mo, Gang Yu, Jia Yu, Shan-min Song, Sha Cheng, Hui-min Li, Xue-ling Meng, Xiao-ping Zeng, Guang-can Xu, Heng Luo, Bi-xue Xu. Discovery of novel 2-(trifluoromethyl)quinolin-4-amine derivatives as potent antitumor agents with microtubule polymerization inhibitory activity. Bioorganic Chemistry 2023, 139 , 106727. https://doi.org/10.1016/j.bioorg.2023.106727
- Yan Cui, Yuxiang Wang, Shu Wang, Bulin Du, Xuena Li, Yaming Li. Highlighting Fibroblasts Activation in Fibrosis: The State-of-The-Art Fibroblast Activation Protein Inhibitor PET Imaging in Cardiovascular Diseases. Journal of Clinical Medicine 2023, 12
(18)
, 6033. https://doi.org/10.3390/jcm12186033
- Tianhong Yang, Lei Peng, Jia Qiu, Xingjin He, Dake Zhang, Renbo Wu, Jianbo Liu, Xiangsong Zhang, Zhihao Zha. A radiohybrid theranostics ligand labeled with fluorine-18 and lutetium-177 for fibroblast activation protein-targeted imaging and radionuclide therapy. European Journal of Nuclear Medicine and Molecular Imaging 2023, 50
(8)
, 2331-2341. https://doi.org/10.1007/s00259-023-06169-5
- Alondra Escudero-Castellanos, Jens Kurth, Surachet Imlimthan, Elena Menéndez, Eirinaios Pilatis, Euy Sung Moon, Tilman Läppchen, Hendrik Rathke, Sarah M. Schwarzenböck, Bernd J. Krause, Frank Rösch, Axel Rominger, Eleni Gourni. Translational assessment of a DATA-functionalized FAP inhibitor with facile 68Ga-labeling at room temperature. European Journal of Nuclear Medicine and Molecular Imaging 2023, 14 https://doi.org/10.1007/s00259-023-06285-2
- Jiawen Huang, LiLan Fu, XiaoJun Zhang, Shun Huang, Ye Dong, Kongzhen Hu, YanJiang Han, Kemin Zhou, Cao Min, YanChao Huang, Ganghua Tang. Noninvasive imaging of FAP expression using positron emission tomography: A comparative evaluation of a [18F]-labeled glycopeptide-containing FAPI with [18F]FAPI-42. European Journal of Nuclear Medicine and Molecular Imaging 2023, 8 https://doi.org/10.1007/s00259-023-06282-5
- Shreya Bendre, Hsiou-Ting Kuo, Helen Merkens, Zhengxing Zhang, Antonio A. W. L. Wong, François Bénard, Kuo-Shyan Lin. Synthesis and Preclinical Evaluation of Novel 68Ga-Labeled (R)-Pyrrolidin-2-yl-boronic Acid-Based PET Tracers for Fibroblast Activation Protein-Targeted Cancer Imaging. Pharmaceuticals 2023, 16
(6)
, 798. https://doi.org/10.3390/ph16060798
- Kunal Ramesh Chandekar, Arun Prashanth, Sobhan Vinjamuri, Rakesh Kumar. FAPI PET/CT Imaging—An Updated Review. Diagnostics 2023, 13
(12)
, 2018. https://doi.org/10.3390/diagnostics13122018
- Frank Roesch, Marcel Martin. Radiometal-theranostics: the first 20 years*. Journal of Radioanalytical and Nuclear Chemistry 2023, 332
(5)
, 1557-1576. https://doi.org/10.1007/s10967-022-08624-3
- Shreya Bendre, Zhengxing Zhang, Nadine Colpo, Jutta Zeisler, Antonio A. W. L. Wong, François Bénard, Kuo-Shyan Lin. Synthesis and Evaluation of 68Ga-Labeled (2S,4S)-4-Fluoropyrrolidine-2-Carbonitrile and (4R)-Thiazolidine-4-Carbonitrile Derivatives as Novel Fibroblast Activation Protein-Targeted PET Tracers for Cancer Imaging. Molecules 2023, 28
(8)
, 3481. https://doi.org/10.3390/molecules28083481
- Yuriko Mori, Clemens Kratochwil, Uwe Haberkorn, Frederik L. Giesel. Fibroblast Activation Protein Inhibitor Theranostics. PET Clinics 2023, 59 https://doi.org/10.1016/j.cpet.2023.02.007
- Ni Zhang, Fei Pan, Lili Pan, Wei Diao, Feijing Su, Rui Huang, Bo Yang, Yunchun Li, Zhongzhi Qi, Wenjie Zhang, Xiaoai Wu. Synthesis, radiolabeling, and evaluation of a (4-quinolinoyl)glycyl-2-cyanopyrrolidine analogue for fibroblast activation protein (FAP) PET imaging. Frontiers in Bioengineering and Biotechnology 2023, 11 https://doi.org/10.3389/fbioe.2023.1167329
- Yuxi Sun, Mengqiu Ma, Dandan Cao, Ancheng Zheng, Yiying Zhang, Yang Su, Jianfang Wang, Yanhua Xu, Mi Zhou, Yansong Tang, Yifan Liu, Teng Ma, Aoyuan Fan, Xiaoying Zhang, Qiaoling Zhu, Jiachen Qin, Chunyang Mo, Yawei Xu, Li Zhang, Dachun Xu, Rui Yue. Inhibition of Fap Promotes Cardiac Repair by Stabilizing BNP. Circulation Research 2023, 132
(5)
, 586-600. https://doi.org/10.1161/CIRCRESAHA.122.320781
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