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Tytuł:
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86Y-Labeled Albumin-Binding Fibroblast Activation Protein Inhibitor for Late-Time-Point Cancer Diagnosis.
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Autorzy:
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Ding J; Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Xu M; Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Chen J; Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Zhang P; Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Huo L; Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Kong Z; Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Liu Z; Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.; Peking University-Tsinghua University Center for Life Sciences, Peking University, Beijing 100871, China.
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Źródło:
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Molecular pharmaceutics [Mol Pharm] 2022 Sep 05; Vol. 19 (9), pp. 3429-3438. Date of Electronic Publication: 2022 Aug 17.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Washington, DC : American Chemical Society, c2004-
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MeSH Terms:
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Carrier Proteins*/metabolism
Neoplasms*/drug therapy
Neoplasms*/metabolism
Albumins/metabolism ; Fibroblasts/metabolism ; Gallium Radioisotopes/metabolism ; Humans ; Membrane Proteins/metabolism ; Positron Emission Tomography Computed Tomography ; Tissue Distribution
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Contributed Indexing:
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Keywords: FAPI; PET; albumin binding; theranostics; tumor retention
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Substance Nomenclature:
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0 (Albumins)
0 (Carrier Proteins)
0 (Gallium Radioisotopes)
0 (Membrane Proteins)
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Entry Date(s):
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Date Created: 20220817 Date Completed: 20220908 Latest Revision: 20220913
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Update Code:
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20240105
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DOI:
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10.1021/acs.molpharmaceut.2c00579
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PMID:
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35976352
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Fibroblast activation protein inhibitor (FAPI) is a novel quinoline-based radiopharmaceutical that has theranostic potential, yet the limited tumor retention hinders late-time diagnosis and radionuclide treatment. This study synthesized four albumin-binding FAPIs (TE-FAPI-01 to 04) and evaluated their in vitro stability, binding affinity, in vivo biodistribution, and tumor uptake with 68 Ga, 86 Y, and 177 Lu labeling, aiming to select the best molecule that has favorable pharmacokinetics to extend the blood circulation and tumor uptake in FAP-expressing tumors. All TE-FAPIs were stable in saline and plasma and displayed high FAP-binding affinity, with IC 50 values ranging from 3.96 to 34.9 nmol/L. The capabilities of TE-FAPIs to be retained in circulation were higher than that of FAPI-04, and TE-FAPI-04 displayed minimum physiological uptake in major organs compared with other molecules. TE-FAPI-03 and TE-FAPI-04 exhibited persistent tumor accumulation, with tumor radioactivity 24 h after administration of 2.84 ± 1.19%ID/g and 3.86 ± 1.15%ID/g for 177 Lu-TE-FAPI-03 and 177 Lu-TE-FAPI-04, respectively, both of which outperformed 177 Lu-FAPI-04 (0.34 ± 0.07%ID/g). TE-FAPI-04 was recognized as the albumin-binding FAPI with the most favorable pharmacokinetics and imaging performance. The enhanced circulation half-life and tumor uptake of TE-FAPI-04 aided the theranostics of malignant tumors and warrant further clinical investigations.
