A Pyroglutamate Aminopeptidase 1 Responsive Fluorescence Imaging Probe for Real-Time Rapid Differentiation between Thyroiditis and Thyroid Cancer
Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid,...
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Veröffentlicht in: | Analytical chemistry (Washington) 2024-04, Vol.96 (15), p.5897-5905 |
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description | Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 μg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivo experiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases. |
doi_str_mv | 10.1021/acs.analchem.3c05872 |
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To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 μg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivo experiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases.</description><identifier>ISSN: 0003-2700</identifier><identifier>ISSN: 1520-6882</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/acs.analchem.3c05872</identifier><identifier>PMID: 38557023</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Aminopeptidase ; aminopeptidases ; analytical chemistry ; Animals ; Biocompatibility ; Biomarkers ; Biopsy ; blood ; Cancer ; carcinoma ; Charge transfer ; detection limit ; Differentiation ; Fluorescence ; Fluorescent Dyes ; Fluorescent indicators ; In vivo methods and tests ; Inflammation ; Irradiation ; Laser radiation ; Medical imaging ; Mice ; Optical Imaging ; photostability ; Pyroglutamyl-Peptidase I ; Real time ; Thyroid ; Thyroid cancer ; Thyroid carcinoma ; Thyroid diseases ; thyroid neoplasms ; Thyroid Neoplasms - diagnostic imaging ; Thyroiditis ; Thyroiditis - pathology ; ultrasonics</subject><ispartof>Analytical chemistry (Washington), 2024-04, Vol.96 (15), p.5897-5905</ispartof><rights>2024 American Chemical Society</rights><rights>Copyright American Chemical Society Apr 16, 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a358t-6ff84cdcb857afca23e34c2e3ea7306678631984d470786116cae567d540a60f3</cites><orcidid>0000-0002-4866-1292 ; 0000-0002-3230-4928</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.analchem.3c05872$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.analchem.3c05872$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2751,27054,27902,27903,56715,56765</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38557023$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Siqi</creatorcontrib><creatorcontrib>Ma, Mo</creatorcontrib><creatorcontrib>Li, Jingkang</creatorcontrib><creatorcontrib>Li, Jiaxin</creatorcontrib><creatorcontrib>Xu, Lanlan</creatorcontrib><creatorcontrib>Gao, Dejiang</creatorcontrib><creatorcontrib>Ma, Pinyi</creatorcontrib><creatorcontrib>Han, Hui</creatorcontrib><creatorcontrib>Song, Daqian</creatorcontrib><title>A Pyroglutamate Aminopeptidase 1 Responsive Fluorescence Imaging Probe for Real-Time Rapid Differentiation between Thyroiditis and Thyroid Cancer</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 μg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivo experiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases.</description><subject>Aminopeptidase</subject><subject>aminopeptidases</subject><subject>analytical chemistry</subject><subject>Animals</subject><subject>Biocompatibility</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>blood</subject><subject>Cancer</subject><subject>carcinoma</subject><subject>Charge transfer</subject><subject>detection limit</subject><subject>Differentiation</subject><subject>Fluorescence</subject><subject>Fluorescent Dyes</subject><subject>Fluorescent indicators</subject><subject>In vivo methods and tests</subject><subject>Inflammation</subject><subject>Irradiation</subject><subject>Laser radiation</subject><subject>Medical imaging</subject><subject>Mice</subject><subject>Optical Imaging</subject><subject>photostability</subject><subject>Pyroglutamyl-Peptidase I</subject><subject>Real time</subject><subject>Thyroid</subject><subject>Thyroid cancer</subject><subject>Thyroid carcinoma</subject><subject>Thyroid diseases</subject><subject>thyroid neoplasms</subject><subject>Thyroid Neoplasms - diagnostic imaging</subject><subject>Thyroiditis</subject><subject>Thyroiditis - pathology</subject><subject>ultrasonics</subject><issn>0003-2700</issn><issn>1520-6882</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAURS0EokPhDxCyxIZNhufYTtzlaKClUiWqalhHb5yXqavEDnYC6mfwx_VoZrpgASvb0rn3yjqMvRewFFCKz2jTEj329p6GpbSgTV2-YAuhSygqY8qXbAEAsihrgDP2JqUHACFAVK_ZmTRa11DKBfuz4rePMez6ecIBJ-Krwfkw0ji5FhNxwe8ojcEn94v4ZT-HSMmSt8SvB9w5v-O3MWyJdyFmEvti4wbidzi6ln9xXUeR_ORwcsHzLU2_iTzf3OdF17rJJY6-Pb35GnNvfMteddgnenc8z9mPy6-b9bfi5vvV9Xp1U6DUZiqqrjPKtnZrdI2dxVKSVLYkSVhLqKraVFJcGNWqGvJdiMoi6aputQKsoJPn7NOhd4zh50xpagaXv9b36CnMqZFCS1ELpeD_KEghpMlzGf34F_oQ5pg17SklL7RSZl-oDpSNIaVIXTNGN2B8bAQ0e7tNttuc7DZHuzn24Vg-bwdqn0MnnRmAA7CPPw__s_MJVHe0sg</recordid><startdate>20240416</startdate><enddate>20240416</enddate><creator>Zhang, Siqi</creator><creator>Ma, Mo</creator><creator>Li, Jingkang</creator><creator>Li, Jiaxin</creator><creator>Xu, Lanlan</creator><creator>Gao, Dejiang</creator><creator>Ma, Pinyi</creator><creator>Han, Hui</creator><creator>Song, Daqian</creator><general>American Chemical Society</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0002-4866-1292</orcidid><orcidid>https://orcid.org/0000-0002-3230-4928</orcidid></search><sort><creationdate>20240416</creationdate><title>A Pyroglutamate Aminopeptidase 1 Responsive Fluorescence Imaging Probe for Real-Time Rapid Differentiation between Thyroiditis and Thyroid Cancer</title><author>Zhang, Siqi ; 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Chem</addtitle><date>2024-04-16</date><risdate>2024</risdate><volume>96</volume><issue>15</issue><spage>5897</spage><epage>5905</epage><pages>5897-5905</pages><issn>0003-2700</issn><issn>1520-6882</issn><eissn>1520-6882</eissn><abstract>Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 μg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivo experiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>38557023</pmid><doi>10.1021/acs.analchem.3c05872</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-4866-1292</orcidid><orcidid>https://orcid.org/0000-0002-3230-4928</orcidid></addata></record> |
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subjects | Aminopeptidase aminopeptidases analytical chemistry Animals Biocompatibility Biomarkers Biopsy blood Cancer carcinoma Charge transfer detection limit Differentiation Fluorescence Fluorescent Dyes Fluorescent indicators In vivo methods and tests Inflammation Irradiation Laser radiation Medical imaging Mice Optical Imaging photostability Pyroglutamyl-Peptidase I Real time Thyroid Thyroid cancer Thyroid carcinoma Thyroid diseases thyroid neoplasms Thyroid Neoplasms - diagnostic imaging Thyroiditis Thyroiditis - pathology ultrasonics |
title | A Pyroglutamate Aminopeptidase 1 Responsive Fluorescence Imaging Probe for Real-Time Rapid Differentiation between Thyroiditis and Thyroid Cancer |
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