{"corpus_id":49577195,"paper_sha":"e4203ce525e4bae37078a4ceac538ddeb9025dc4","doi":"10.7150/thno.23853","arxiv_id":null,"pmid":30026858,"pmcid":"6037036","mag_id":2806423326,"dblp_id":null,"acl_id":null,"title":"Image-guided surgery using near-infrared Turn-ON fluorescent nanoprobes for precise detection of tumor margins","year":2018,"publication_date":"2018-05-24","venue":"Theranostics","journal":{"name":"Theranostics","pages":"3437 - 3460","volume":"8"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine","Materials Science","Engineering"],"reference_count":85,"citation_count":57,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Breast Neoplasms","mj":false,"qs":[{"q":"surgery","mj":true,"ui":"Q000601"}],"ui":"D001943"},{"d":"Cathepsins","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D002403"},{"d":"Disease Models, Animal","mj":false,"ui":"D004195"},{"d":"Fluorescent Dyes","mj":false,"qs":[{"q":"administration & dosage","mj":false,"ui":"Q000008"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D005456"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Melanoma","mj":false,"qs":[{"q":"surgery","mj":true,"ui":"Q000601"}],"ui":"D008545"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Nanoparticles","mj":false,"qs":[{"q":"administration & dosage","mj":true,"ui":"Q000008"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D053758"},{"d":"Optical Imaging","mj":false,"qs":[{"q":"methods","mj":true,"ui":"Q000379"}],"ui":"D061848"},{"d":"Staining and Labeling","mj":false,"qs":[{"q":"methods","mj":true,"ui":"Q000379"}],"ui":"D013194"},{"d":"Surgery, Computer-Assisted","mj":false,"qs":[{"q":"methods","mj":true,"ui":"Q000379"}],"ui":"D025321"},{"d":"Treatment Outcome","mj":false,"ui":"D016896"}],"chemicals":[{"n":"Fluorescent Dyes","ui":"D005456","reg":"0"},{"n":"Cathepsins","ui":"D002403","reg":"EC 3.4.-"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Complete tumor removal during surgery has a great impact on patient survival. To that end, the surgeon should detect the tumor, remove it and validate that there are no residual cancer cells left behind. Residual cells at the incision margin of the tissue removed during surgery are associated with tumor recurrence and poor prognosis for the patient. In order to remove the tumor tissue completely with minimal collateral damage to healthy tissue, there is a need for diagnostic tools that will differentiate between the tumor and its normal surroundings. Methods: We designed, synthesized and characterized three novel polymeric Turn-ON probes that will be activated at the tumor site by cysteine cathepsins that are highly expressed in multiple tumor types. Utilizing orthotopic breast cancer and melanoma models, which spontaneously metastasize to the brain, we studied the kinetics of our polymeric Turn-ON nano-probes. Results: To date, numerous low molecular weight cathepsin-sensitive substrates have been reported, however, most of them suffer from rapid clearance and reduced signal shortly after administration. Here, we show an improved tumor-to-background ratio upon activation of our Turn-ON probes by cathepsins. The signal obtained from the tumor was stable and delineated the tumor boundaries during the whole surgical procedure, enabling accurate resection. Conclusions: Our findings show that the control groups of tumor-bearing mice, which underwent either standard surgery under white light only or under the fluorescence guidance of the commercially-available imaging agents ProSense® 680 or 5-aminolevulinic acid (5-ALA), survived for less time and suffered from tumor recurrence earlier than the group that underwent image-guided surgery (IGS) using our Turn-ON probes. Our \"smart\" polymeric probes can potentially assist surgeons' decision in real-time during surgery regarding the tumor margins needed to be removed, leading to improved patient outcome.","claims":[{"public_id":"cl_9dfd74858fe4a41948755600140a173d","status":"active","text":"Activation of the polymeric Turn-ON probes by cysteine cathepsins produces an improved tumor-to-background ratio.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_9dfd74858fe4a41948755600140a173d"},{"public_id":"cl_80785c0f2146307cc797dfa0a8082aac","status":"active","text":"Image-guided surgery using the Turn-ON probes leads to longer survival and later tumor recurrence than standard white-light surgery, ProSense® 680-guided surgery, or 5-aminolevulinic acid-guided surgery in tumor-bearing mice.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_80785c0f2146307cc797dfa0a8082aac"},{"public_id":"cl_835dc4a4625d6b7e32ac24f95f447601","status":"active","text":"The probes can support real-time intraoperative decisions about tumor margins to remove.","confidence":0.9,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_835dc4a4625d6b7e32ac24f95f447601"},{"public_id":"cl_894e5b0385af9606f8f9689117eb50b4","status":"active","text":"The tumor signal remains stable throughout the surgical procedure and delineates tumor boundaries, enabling accurate resection.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_894e5b0385af9606f8f9689117eb50b4"}],"concepts":[{"public_id":"co_042c0e7e4a4c7d7efae4b5c8f910195b","status":"active","name":"tumor-to-background ratio","description":"The contrast between signal from tumor tissue and surrounding non-tumor tissue.","types":["measurement"],"aliases":["TBR"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_042c0e7e4a4c7d7efae4b5c8f910195b"},{"public_id":"co_139819cc2ad26f1521b2d4031d184bc9","status":"active","name":"image-guided surgery","description":"Surgery performed with imaging assistance to identify tumor tissue and guide resection.","types":["surgical approach","method"],"aliases":["IGS"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_139819cc2ad26f1521b2d4031d184bc9"},{"public_id":"co_21f9a38fbe1f08c0a102537d4f340136","status":"active","name":"tumor recurrence","description":"Return of tumor growth after surgical treatment.","types":["outcome","clinical outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_21f9a38fbe1f08c0a102537d4f340136"},{"public_id":"co_4b3641d46fe8b8eb323b59bc239d6e34","status":"active","name":"ProSense® 680","description":"A commercially available fluorescence imaging agent used as a comparison in surgery.","types":["imaging agent","comparison"],"aliases":["ProSense 680"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_4b3641d46fe8b8eb323b59bc239d6e34"},{"public_id":"co_531247db5672194648b61a0db0137f7b","status":"active","name":"5-aminolevulinic acid","description":"A fluorescent imaging precursor used as a comparison in fluorescence-guided surgery.","types":["imaging agent","comparison"],"aliases":["5-ALA"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_531247db5672194648b61a0db0137f7b"},{"public_id":"co_5bbc3aa0a0a4d4c7e160e26d82d229bb","status":"active","name":"tumor signal","description":"The fluorescent signal emitted from tumor tissue after probe activation.","types":["imaging signal"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_5bbc3aa0a0a4d4c7e160e26d82d229bb"},{"public_id":"co_61861dc25add7b6d8954a4d240e7d2ce","status":"active","name":"cysteine cathepsins","description":"Tumor-associated proteases that activate the probes at the tumor site.","types":["enzyme","biomarker"],"aliases":["cathepsins"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_61861dc25add7b6d8954a4d240e7d2ce"},{"public_id":"co_73a68d41f920edf89c7bf4df76831653","status":"active","name":"surgical procedure","description":"The intraoperative period during which tumor removal and margin assessment are performed.","types":["procedure"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_73a68d41f920edf89c7bf4df76831653"},{"public_id":"co_84b3b0495425b05350cd9b1f775e1f19","status":"active","name":"tumor margins","description":"The boundary region between tumor tissue and adjacent normal tissue.","types":["anatomical region","surgical target"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_84b3b0495425b05350cd9b1f775e1f19"},{"public_id":"co_893b6875b072a93290f4b0a89d03843a","status":"active","name":"Turn-ON probes","description":"Fluorescent probes that switch from low to high signal when activated in the target environment.","types":["probe","method"],"aliases":["polymeric Turn-ON probes","smart polymeric probes"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_893b6875b072a93290f4b0a89d03843a"},{"public_id":"co_8cbee3432347dc7aabe503558bf4548c","status":"active","name":"polymeric Turn-ON probes","description":"Polymer-based fluorescent nanoprobes that become activated to emit signal at the tumor site.","types":["method","probe"],"aliases":["Turn-ON probes","polymeric Turn-ON nanoprobes","smart polymeric probes"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_8cbee3432347dc7aabe503558bf4548c"},{"public_id":"co_e4eace95d992f21d280cee7a096c1d90","status":"active","name":"real-time decision","description":"Intraoperative judgment made immediately during surgery based on imaging information.","types":["decision support"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_e4eace95d992f21d280cee7a096c1d90"},{"public_id":"co_ec1a885ab596e28374c87bed69de0bb6","status":"active","name":"accurate resection","description":"Tumor removal that follows the visible tumor boundaries while minimizing residual disease.","types":["outcome","surgical outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_ec1a885ab596e28374c87bed69de0bb6"}],"external_ids":{"DOI":"10.7150/thno.23853","ArXiv":null,"PubMed":30026858,"PubMedCentral":"6037036","MAG":2806423326,"DBLP":null,"ACL":null},"open_access":{"is_open_access":false,"pdf_url":null,"landing_url":"https://sah.borca.ai/papers/49577195","source":null,"pdf_url_source":null,"license":null,"reason":"pdf_url_not_indexed"},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":638314,"paper_uid":"918c8d04-53a7-45dc-9bfe-728322445e16","canonical_identity":{"paper_id":638314,"paper_uid":"918c8d04-53a7-45dc-9bfe-728322445e16","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/49577195"}