{"doi":"10.3171/2020.4.jns192476","title":"Provision of rapid and specific ex vivo diagnosis of central nervous system lymphoma from rodent xenograft biopsies by a fluorescent aptamer","abstract":"OBJECTIVE: Differentiating central nervous system (CNS) lymphoma from other intracranial malignancies remains a clinical challenge in surgical neuro-oncology. Advances in clinical fluorescence imaging contrast agents and devices may mitigate this challenge. Aptamers are a class of nanomolecules engineered to bind cellular targets with antibody-like specificity in a fraction of the staining time. Here, the authors determine if immediate ex vivo fluorescence imaging with a lymphoma-specific aptamer can rapidly and specifically diagnose xenografted orthotopic human CNS lymphoma at the time of biopsy. METHODS: The authors synthesized a fluorescent CNS lymphoma-specific aptamer by conjugating a lymphoma-specific aptamer with Alexa Fluor 488 (TD05-488). They modified human U251 glioma cells and Ramos lymphoma cells with a lentivirus for constitutive expression of red fluorescent protein and implanted them intracranially into athymic nude mice. Three to 4 weeks postimplantation, acute slices (biopsies, n = 28) from the xenografts were collected, placed in aptamer solution, and imaged with a Zeiss fluorescence microscope. Three aptamer staining concentrations (0.3, 1.0, and 3.0 μM) and three staining times (5, 10, and 20 minutes) followed by a 1-minute wash were tested. A file of randomly selected images was distributed to neurosurgeons and neuropathologists, and their ability to distinguish CNS lymphoma from negative controls was assessed. RESULTS: The three staining times and concentrations of TD05-488 were tested to determine the diagnostic accuracy of CNS lymphoma within a frozen section time frame. An 11-minute staining protocol with 1.0-μM TD05-488 was most efficient, labeling 77% of positive control lymphoma cells and less than 1% of negative control glioma cells (p < 0.001). This protocol permitted clinicians to positively identify all positive control lymphoma images without misdiagnosing negative control images from astrocytoma and normal brain. CONCLUSIONS: Ex vivo fluorescence imaging is an emerging technique for generating rapid histopathological diagnoses. Ex vivo imaging with a novel aptamer-based fluorescent nanomolecule could provide an intraoperative tumor-specific diagnosis of CNS lymphoma within 11 minutes of biopsy. Neurosurgeons and neuropathologists interpreted images generated with this molecular probe with high sensitivity and specificity. Clinical application of TD05-488 may permit specific intraoperative diagnosis of CNS lymphoma in a fraction of the time required for antibody staining.","journal":"Journal of neurosurgery","year":2020,"id":111173,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.961,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":528332,"name":"Xiaodong Qi","orcid":"0000-0001-8200-6630","position":1,"is_corresponding":false},{"id":417694,"name":"Xiaowei Liu","orcid":"0000-0002-2015-4176","position":2,"is_corresponding":false},{"id":528333,"name":"Yu Zhou","orcid":"0000-0002-1623-7948","position":3,"is_corresponding":false},{"id":529149,"name":"Eric C. Woolf","orcid":null,"position":4,"is_corresponding":false},{"id":377527,"name":"Amber Valeri","orcid":null,"position":5,"is_corresponding":false},{"id":528334,"name":"Zein Al-Atrache","orcid":"0000-0002-1561-9290","position":6,"is_corresponding":false},{"id":528335,"name":"Evgenii Belykh","orcid":"0000-0003-2060-5739","position":7,"is_corresponding":false},{"id":528336,"name":"Burt G. Feuerstein","orcid":"0000-0001-7276-8842","position":8,"is_corresponding":false},{"id":528337,"name":"Mark C. Preul","orcid":"0000-0002-3477-4931","position":9,"is_corresponding":false},{"id":528338,"name":"Adrienne C. Scheck","orcid":"0000-0003-3497-1895","position":10,"is_corresponding":false},{"id":529150,"name":"Mark Reiser","orcid":null,"position":11,"is_corresponding":false},{"id":395701,"name":"Trent Anderson","orcid":"0000-0002-3541-7741","position":12,"is_corresponding":false},{"id":529151,"name":"Jonas Gopez","orcid":null,"position":13,"is_corresponding":false},{"id":362110,"name":"Denah M. Appelt","orcid":"0000-0002-0720-4722","position":14,"is_corresponding":false},{"id":529152,"name":"Steven Yocom","orcid":null,"position":15,"is_corresponding":false},{"id":69772,"name":"Jennifer Eschbacher","orcid":"0000-0002-2599-0819","position":16,"is_corresponding":false},{"id":275749,"name":"Hao Yan","orcid":"0000-0001-7397-9852","position":17,"is_corresponding":false},{"id":307329,"name":"Peter Nakaji","orcid":"0000-0001-6677-2925","position":18,"is_corresponding":false},{"id":362105,"name":"Joseph Georges","orcid":"0000-0002-7630-8007","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:13:05.597252Z","pmid":"32707545","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}