Development and preclinical evaluation of a cyclic PET tracer targeting integrin-α6 on colorectal cancer models
[Display omitted] •A cyclic peptide A6P targeting integrin-α6 was developed, which exhibited the potent binding affinity targeted integrin-α6 (Kd = 13.40 ± 3.41 nM).•A promising PET tracer [18F]AlF-NOTA-A6P with high radiochemical yield (RCY: 58.1 ± 4.1 %) was synthesized in a novel cassette-type sy...
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| creator | Chen, Liping Fu, Haitian Li, Wenjin Shen, Qiaolin Luo, Yihui Fu, Junjie Shao, Chong He, Huihui Lou, Kequan Wang, Jialiang Feng, Guokai Yu, Chunjing |
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•A cyclic peptide A6P targeting integrin-α6 was developed, which exhibited the potent binding affinity targeted integrin-α6 (Kd = 13.40 ± 3.41 nM).•A promising PET tracer [18F]AlF-NOTA-A6P with high radiochemical yield (RCY: 58.1 ± 4.1 %) was synthesized in a novel cassette-type synthesis module (Mortenon M1).•[18F]AlF-NOTA-A6P has achieved significant improvements in affinity, stability, tumor uptake and retention time over previous tracer [18F]AlF-NOTA-RD2.•Providing a promising non-invasive PET radiotracer for the detection of colorectal cancer.
Integrin-α6 is an attractive diagnostic and therapeutic biomarker in cancer, because it is highly expressed in several types of malignancies. Based on our previous findings, we designed a cyclic peptide, NOTA-A6P, to enhancing affinity, tumor uptake and serum stability, and then developed a cyclic radiotracer, [18F]AlF-NOTA-A6P, for the specific detection of early colorectal cancer by PET/CT imaging. [18F] AlF-NOTA-A6P was automatically labeled for colorectal cancer imaging in a novel synthesis module. The affinity, stability, radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), and octanol–water partition coefficient of [18F]AlF-NOTA-A6P were investigated. Results demonstrated that the tracer exhibited high serum stability, high RCY (58.1 ± 4.1 %) (undecay-corrected, n = 5) and hydrophilicity. In vivo microPET/CT imaging of LS174T and HT29 xenograft tumor models with high integrin-α6 expression indicated that [18F]AlF-NOTA-A6P exhibited higher tumor uptake and tumor-to-muscle ratio than SW620, which has low integrin-α6 expression. Moreover, the specificity of [18F]AlF-NOTA-A6P for integrin-α6 was confirmed by additional methods, including autoradiography, hematoxylin and eosin staining, and immunohistochemical staining. In conclusion, a cyclic peptide NOTA-A6P targeting integrin-α6 was designed and a promising PET tracer [18F]AlF-NOTA-A6P was synthesized in a novel cassette-type synthesis module. The tracer demonstrated a favorable binding affinity with integrin-α6, stability in human serum and specificity for colorectal cancer xenograft mice. These properties render it a promising non-invasive PET radiotracer for the detection of integrin-α6-overexpressing cancers, including colorectal cancer. |
| doi_str_mv | 10.1016/j.bioorg.2024.107892 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3120596306</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0045206824007971</els_id><sourcerecordid>3120596306</sourcerecordid><originalsourceid>FETCH-LOGICAL-c241t-1b86b856d805c37edfd6d742ea0c87399935e9bcd3e24189fc84e0081a675ec33</originalsourceid><addsrcrecordid>eNp9kM2OFCEURonROO3oGxjD0k21UFAUbEzMOP4kk-hiXBMKbnXoUFAC3ck8li_iM0mnRpeubsI933fDQeg1JXtKqHh33E8-pXzY96Tn7WmUqn-CdpQo0vW0J0_RjhA-dD0R8gq9KOVICKV8FM_RFVOcj4yLHVo_whlCWheIFZvo8JrBBh-9NQHD2YSTqT5FnGZssH1oK4u_397jmo2FjKvJB6g-HrCPFQ7Zx-73L4FbwKaQWlVtNdbEC7skB6G8RM9mEwq8epzX6Men2_ubL93dt89fbz7cdbbntHZ0kmKSg3CSDJaN4GYn3Mh7MMTKkSml2ABqso5B46WareRAiKRGjANYxq7R2613zennCUrViy8WQjAR0qlo1hQNSjAiGso31OZUSoZZr9kvJj9oSvTFtT7qzbW-uNab6xZ783jhNC3g_oX-ym3A-w1o34azh6yL9dBcOH8xo13y_7_wBzy2k1M</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3120596306</pqid></control><display><type>article</type><title>Development and preclinical evaluation of a cyclic PET tracer targeting integrin-α6 on colorectal cancer models</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Chen, Liping ; Fu, Haitian ; Li, Wenjin ; Shen, Qiaolin ; Luo, Yihui ; Fu, Junjie ; Shao, Chong ; He, Huihui ; Lou, Kequan ; Wang, Jialiang ; Feng, Guokai ; Yu, Chunjing</creator><creatorcontrib>Chen, Liping ; Fu, Haitian ; Li, Wenjin ; Shen, Qiaolin ; Luo, Yihui ; Fu, Junjie ; Shao, Chong ; He, Huihui ; Lou, Kequan ; Wang, Jialiang ; Feng, Guokai ; Yu, Chunjing</creatorcontrib><description>[Display omitted]
•A cyclic peptide A6P targeting integrin-α6 was developed, which exhibited the potent binding affinity targeted integrin-α6 (Kd = 13.40 ± 3.41 nM).•A promising PET tracer [18F]AlF-NOTA-A6P with high radiochemical yield (RCY: 58.1 ± 4.1 %) was synthesized in a novel cassette-type synthesis module (Mortenon M1).•[18F]AlF-NOTA-A6P has achieved significant improvements in affinity, stability, tumor uptake and retention time over previous tracer [18F]AlF-NOTA-RD2.•Providing a promising non-invasive PET radiotracer for the detection of colorectal cancer.
Integrin-α6 is an attractive diagnostic and therapeutic biomarker in cancer, because it is highly expressed in several types of malignancies. Based on our previous findings, we designed a cyclic peptide, NOTA-A6P, to enhancing affinity, tumor uptake and serum stability, and then developed a cyclic radiotracer, [18F]AlF-NOTA-A6P, for the specific detection of early colorectal cancer by PET/CT imaging. [18F] AlF-NOTA-A6P was automatically labeled for colorectal cancer imaging in a novel synthesis module. The affinity, stability, radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), and octanol–water partition coefficient of [18F]AlF-NOTA-A6P were investigated. Results demonstrated that the tracer exhibited high serum stability, high RCY (58.1 ± 4.1 %) (undecay-corrected, n = 5) and hydrophilicity. In vivo microPET/CT imaging of LS174T and HT29 xenograft tumor models with high integrin-α6 expression indicated that [18F]AlF-NOTA-A6P exhibited higher tumor uptake and tumor-to-muscle ratio than SW620, which has low integrin-α6 expression. Moreover, the specificity of [18F]AlF-NOTA-A6P for integrin-α6 was confirmed by additional methods, including autoradiography, hematoxylin and eosin staining, and immunohistochemical staining. In conclusion, a cyclic peptide NOTA-A6P targeting integrin-α6 was designed and a promising PET tracer [18F]AlF-NOTA-A6P was synthesized in a novel cassette-type synthesis module. The tracer demonstrated a favorable binding affinity with integrin-α6, stability in human serum and specificity for colorectal cancer xenograft mice. These properties render it a promising non-invasive PET radiotracer for the detection of integrin-α6-overexpressing cancers, including colorectal cancer.</description><identifier>ISSN: 0045-2068</identifier><identifier>ISSN: 1090-2120</identifier><identifier>EISSN: 1090-2120</identifier><identifier>DOI: 10.1016/j.bioorg.2024.107892</identifier><identifier>PMID: 39447346</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>[18F]AlF-NOTA-A6P ; Animals ; Automated synthesis ; Colorectal cancer ; Colorectal Neoplasms - diagnostic imaging ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Cyclic peptide ; Female ; Fluorine Radioisotopes - chemistry ; Humans ; Integrin alpha6 - metabolism ; Integrin-α6 ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Structure ; Neoplasms, Experimental - diagnostic imaging ; Neoplasms, Experimental - metabolism ; Peptides, Cyclic - chemical synthesis ; Peptides, Cyclic - chemistry ; Peptides, Cyclic - pharmacokinetics ; Positron emission tomography ; Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals - chemical synthesis ; Radiopharmaceuticals - chemistry ; Structure-Activity Relationship ; Tissue Distribution</subject><ispartof>Bioorganic chemistry, 2024-12, Vol.153, p.107892, Article 107892</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c241t-1b86b856d805c37edfd6d742ea0c87399935e9bcd3e24189fc84e0081a675ec33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bioorg.2024.107892$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39447346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Liping</creatorcontrib><creatorcontrib>Fu, Haitian</creatorcontrib><creatorcontrib>Li, Wenjin</creatorcontrib><creatorcontrib>Shen, Qiaolin</creatorcontrib><creatorcontrib>Luo, Yihui</creatorcontrib><creatorcontrib>Fu, Junjie</creatorcontrib><creatorcontrib>Shao, Chong</creatorcontrib><creatorcontrib>He, Huihui</creatorcontrib><creatorcontrib>Lou, Kequan</creatorcontrib><creatorcontrib>Wang, Jialiang</creatorcontrib><creatorcontrib>Feng, Guokai</creatorcontrib><creatorcontrib>Yu, Chunjing</creatorcontrib><title>Development and preclinical evaluation of a cyclic PET tracer targeting integrin-α6 on colorectal cancer models</title><title>Bioorganic chemistry</title><addtitle>Bioorg Chem</addtitle><description>[Display omitted]
•A cyclic peptide A6P targeting integrin-α6 was developed, which exhibited the potent binding affinity targeted integrin-α6 (Kd = 13.40 ± 3.41 nM).•A promising PET tracer [18F]AlF-NOTA-A6P with high radiochemical yield (RCY: 58.1 ± 4.1 %) was synthesized in a novel cassette-type synthesis module (Mortenon M1).•[18F]AlF-NOTA-A6P has achieved significant improvements in affinity, stability, tumor uptake and retention time over previous tracer [18F]AlF-NOTA-RD2.•Providing a promising non-invasive PET radiotracer for the detection of colorectal cancer.
Integrin-α6 is an attractive diagnostic and therapeutic biomarker in cancer, because it is highly expressed in several types of malignancies. Based on our previous findings, we designed a cyclic peptide, NOTA-A6P, to enhancing affinity, tumor uptake and serum stability, and then developed a cyclic radiotracer, [18F]AlF-NOTA-A6P, for the specific detection of early colorectal cancer by PET/CT imaging. [18F] AlF-NOTA-A6P was automatically labeled for colorectal cancer imaging in a novel synthesis module. The affinity, stability, radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), and octanol–water partition coefficient of [18F]AlF-NOTA-A6P were investigated. Results demonstrated that the tracer exhibited high serum stability, high RCY (58.1 ± 4.1 %) (undecay-corrected, n = 5) and hydrophilicity. In vivo microPET/CT imaging of LS174T and HT29 xenograft tumor models with high integrin-α6 expression indicated that [18F]AlF-NOTA-A6P exhibited higher tumor uptake and tumor-to-muscle ratio than SW620, which has low integrin-α6 expression. Moreover, the specificity of [18F]AlF-NOTA-A6P for integrin-α6 was confirmed by additional methods, including autoradiography, hematoxylin and eosin staining, and immunohistochemical staining. In conclusion, a cyclic peptide NOTA-A6P targeting integrin-α6 was designed and a promising PET tracer [18F]AlF-NOTA-A6P was synthesized in a novel cassette-type synthesis module. The tracer demonstrated a favorable binding affinity with integrin-α6, stability in human serum and specificity for colorectal cancer xenograft mice. These properties render it a promising non-invasive PET radiotracer for the detection of integrin-α6-overexpressing cancers, including colorectal cancer.</description><subject>[18F]AlF-NOTA-A6P</subject><subject>Animals</subject><subject>Automated synthesis</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - diagnostic imaging</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Cyclic peptide</subject><subject>Female</subject><subject>Fluorine Radioisotopes - chemistry</subject><subject>Humans</subject><subject>Integrin alpha6 - metabolism</subject><subject>Integrin-α6</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Molecular Structure</subject><subject>Neoplasms, Experimental - diagnostic imaging</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Peptides, Cyclic - chemical synthesis</subject><subject>Peptides, Cyclic - chemistry</subject><subject>Peptides, Cyclic - pharmacokinetics</subject><subject>Positron emission tomography</subject><subject>Positron Emission Tomography Computed Tomography</subject><subject>Radiopharmaceuticals - chemical synthesis</subject><subject>Radiopharmaceuticals - chemistry</subject><subject>Structure-Activity Relationship</subject><subject>Tissue Distribution</subject><issn>0045-2068</issn><issn>1090-2120</issn><issn>1090-2120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM2OFCEURonROO3oGxjD0k21UFAUbEzMOP4kk-hiXBMKbnXoUFAC3ck8li_iM0mnRpeubsI933fDQeg1JXtKqHh33E8-pXzY96Tn7WmUqn-CdpQo0vW0J0_RjhA-dD0R8gq9KOVICKV8FM_RFVOcj4yLHVo_whlCWheIFZvo8JrBBh-9NQHD2YSTqT5FnGZssH1oK4u_397jmo2FjKvJB6g-HrCPFQ7Zx-73L4FbwKaQWlVtNdbEC7skB6G8RM9mEwq8epzX6Men2_ubL93dt89fbz7cdbbntHZ0kmKSg3CSDJaN4GYn3Mh7MMTKkSml2ABqso5B46WareRAiKRGjANYxq7R2613zennCUrViy8WQjAR0qlo1hQNSjAiGso31OZUSoZZr9kvJj9oSvTFtT7qzbW-uNab6xZ783jhNC3g_oX-ym3A-w1o34azh6yL9dBcOH8xo13y_7_wBzy2k1M</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Chen, Liping</creator><creator>Fu, Haitian</creator><creator>Li, Wenjin</creator><creator>Shen, Qiaolin</creator><creator>Luo, Yihui</creator><creator>Fu, Junjie</creator><creator>Shao, Chong</creator><creator>He, Huihui</creator><creator>Lou, Kequan</creator><creator>Wang, Jialiang</creator><creator>Feng, Guokai</creator><creator>Yu, Chunjing</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202412</creationdate><title>Development and preclinical evaluation of a cyclic PET tracer targeting integrin-α6 on colorectal cancer models</title><author>Chen, Liping ; Fu, Haitian ; Li, Wenjin ; Shen, Qiaolin ; Luo, Yihui ; Fu, Junjie ; Shao, Chong ; He, Huihui ; Lou, Kequan ; Wang, Jialiang ; Feng, Guokai ; Yu, Chunjing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c241t-1b86b856d805c37edfd6d742ea0c87399935e9bcd3e24189fc84e0081a675ec33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>[18F]AlF-NOTA-A6P</topic><topic>Animals</topic><topic>Automated synthesis</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - diagnostic imaging</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Cyclic peptide</topic><topic>Female</topic><topic>Fluorine Radioisotopes - chemistry</topic><topic>Humans</topic><topic>Integrin alpha6 - metabolism</topic><topic>Integrin-α6</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Molecular Structure</topic><topic>Neoplasms, Experimental - diagnostic imaging</topic><topic>Neoplasms, Experimental - metabolism</topic><topic>Peptides, Cyclic - chemical synthesis</topic><topic>Peptides, Cyclic - chemistry</topic><topic>Peptides, Cyclic - pharmacokinetics</topic><topic>Positron emission tomography</topic><topic>Positron Emission Tomography Computed Tomography</topic><topic>Radiopharmaceuticals - chemical synthesis</topic><topic>Radiopharmaceuticals - chemistry</topic><topic>Structure-Activity Relationship</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Liping</creatorcontrib><creatorcontrib>Fu, Haitian</creatorcontrib><creatorcontrib>Li, Wenjin</creatorcontrib><creatorcontrib>Shen, Qiaolin</creatorcontrib><creatorcontrib>Luo, Yihui</creatorcontrib><creatorcontrib>Fu, Junjie</creatorcontrib><creatorcontrib>Shao, Chong</creatorcontrib><creatorcontrib>He, Huihui</creatorcontrib><creatorcontrib>Lou, Kequan</creatorcontrib><creatorcontrib>Wang, Jialiang</creatorcontrib><creatorcontrib>Feng, Guokai</creatorcontrib><creatorcontrib>Yu, Chunjing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Liping</au><au>Fu, Haitian</au><au>Li, Wenjin</au><au>Shen, Qiaolin</au><au>Luo, Yihui</au><au>Fu, Junjie</au><au>Shao, Chong</au><au>He, Huihui</au><au>Lou, Kequan</au><au>Wang, Jialiang</au><au>Feng, Guokai</au><au>Yu, Chunjing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development and preclinical evaluation of a cyclic PET tracer targeting integrin-α6 on colorectal cancer models</atitle><jtitle>Bioorganic chemistry</jtitle><addtitle>Bioorg Chem</addtitle><date>2024-12</date><risdate>2024</risdate><volume>153</volume><spage>107892</spage><pages>107892-</pages><artnum>107892</artnum><issn>0045-2068</issn><issn>1090-2120</issn><eissn>1090-2120</eissn><abstract>[Display omitted]
•A cyclic peptide A6P targeting integrin-α6 was developed, which exhibited the potent binding affinity targeted integrin-α6 (Kd = 13.40 ± 3.41 nM).•A promising PET tracer [18F]AlF-NOTA-A6P with high radiochemical yield (RCY: 58.1 ± 4.1 %) was synthesized in a novel cassette-type synthesis module (Mortenon M1).•[18F]AlF-NOTA-A6P has achieved significant improvements in affinity, stability, tumor uptake and retention time over previous tracer [18F]AlF-NOTA-RD2.•Providing a promising non-invasive PET radiotracer for the detection of colorectal cancer.
Integrin-α6 is an attractive diagnostic and therapeutic biomarker in cancer, because it is highly expressed in several types of malignancies. Based on our previous findings, we designed a cyclic peptide, NOTA-A6P, to enhancing affinity, tumor uptake and serum stability, and then developed a cyclic radiotracer, [18F]AlF-NOTA-A6P, for the specific detection of early colorectal cancer by PET/CT imaging. [18F] AlF-NOTA-A6P was automatically labeled for colorectal cancer imaging in a novel synthesis module. The affinity, stability, radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), and octanol–water partition coefficient of [18F]AlF-NOTA-A6P were investigated. Results demonstrated that the tracer exhibited high serum stability, high RCY (58.1 ± 4.1 %) (undecay-corrected, n = 5) and hydrophilicity. In vivo microPET/CT imaging of LS174T and HT29 xenograft tumor models with high integrin-α6 expression indicated that [18F]AlF-NOTA-A6P exhibited higher tumor uptake and tumor-to-muscle ratio than SW620, which has low integrin-α6 expression. Moreover, the specificity of [18F]AlF-NOTA-A6P for integrin-α6 was confirmed by additional methods, including autoradiography, hematoxylin and eosin staining, and immunohistochemical staining. In conclusion, a cyclic peptide NOTA-A6P targeting integrin-α6 was designed and a promising PET tracer [18F]AlF-NOTA-A6P was synthesized in a novel cassette-type synthesis module. The tracer demonstrated a favorable binding affinity with integrin-α6, stability in human serum and specificity for colorectal cancer xenograft mice. These properties render it a promising non-invasive PET radiotracer for the detection of integrin-α6-overexpressing cancers, including colorectal cancer.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39447346</pmid><doi>10.1016/j.bioorg.2024.107892</doi></addata></record> |
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| subjects | [18F]AlF-NOTA-A6P Animals Automated synthesis Colorectal cancer Colorectal Neoplasms - diagnostic imaging Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Cyclic peptide Female Fluorine Radioisotopes - chemistry Humans Integrin alpha6 - metabolism Integrin-α6 Mice Mice, Inbred BALB C Mice, Nude Molecular Structure Neoplasms, Experimental - diagnostic imaging Neoplasms, Experimental - metabolism Peptides, Cyclic - chemical synthesis Peptides, Cyclic - chemistry Peptides, Cyclic - pharmacokinetics Positron emission tomography Positron Emission Tomography Computed Tomography Radiopharmaceuticals - chemical synthesis Radiopharmaceuticals - chemistry Structure-Activity Relationship Tissue Distribution |
| title | Development and preclinical evaluation of a cyclic PET tracer targeting integrin-α6 on colorectal cancer models |
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