Molecular Diagnosis & Therapy最新文献

{"title":"Analytical and Clinical Validation of the Oncomine Dx Express Test, an In Vitro Diagnostic-Labeled Assay, for Genomic Profiling of FFPE Tumor Samples.","authors":"Angie Cheng, Sumitha Nallu, Luming He, April Bigley, Aline Bridi, Emilia Ostrowska, Thilanka Jayaweera, Madhu Jasti, Daniela Garcia, Molly Fehon, Thomas Bowden, Nader Ezzedine, Diarra Hassel, Swasti Raut, Erik Breitenfeldt, Alina Dykman, Tasha Delacour, Brian Hradecky, Andrew Hatch, Stephen Wunsch, Gokhan Yavas, Del Rodrigo, Jeoffrey Schageman, Elena Kuzmenko, Jessie Wang, Vrunda Sheth, Eun Ji Kim, Hsueh Ping Chao, John Williamson, Hans Gripkey, José Luis Costa, Cecília Durães, Anne Marie Velasco Roth","doi":"10.1007/s40291-026-00884-z","DOIUrl":"https://doi.org/10.1007/s40291-026-00884-z","url":null,"abstract":"<p><strong>Background: </strong>Genomic profiling of solid tumors by next-generation sequencing (NGS) supports personalized therapy selection, but routine clinical adoption requires robust analytical and clinical validation. The Oncomine™ Dx Express Test (ODxET) is a companion diagnostic and tumor profiling in vitro diagnostic NGS assay for detecting targeted single- and multinucleotide variants (SNVs/MNVs), insertions, deletions, copy number variations (CNVs), and RNA fusions or splice variants in formalin-fixed, paraffin-embedded (FFPE) solid tumor samples.</p><p><strong>Methods: </strong>In a retrospective, blinded analytical study, 462 FFPE samples representing 15 tumor types and including 76 wild-type samples, were analyzed with ODxET and compared with validated orthogonal methods. Reproducibility and repeatability were evaluated across three sites, each using two operators, two sequencers, three reagent lots, and two replicates. Clinical performance for epidermal growth factor receptor (EGFR) exon 20 insertion detection was assessed using non-small cell lung cancer (NSCLC) samples from the WU-KONG1B sunvozertinib clinical trial and commercially sourced biomarker-negative specimens, with clinical effectiveness evaluated in patients treated with the approved sunvozertinib dose.</p><p><strong>Results: </strong>The ODxET assay showed high analytical concordance for EGFR exon 20 insertions, with a positive percent agreement (PPA) of 100% and a negative percent agreement (NPA) of 95.5%. Across the reportable range of profiling variant classes, the ODxET assay also showed high analytical concordance with orthogonal methods for SNVs (PPA = 99.5%, NPA = 100%), insertions and deletions (PPA and NPA = 100%), CNVs (PPA = 94.2%, NPA = 99.3%), and RNA variants (PPA = 95.9%, NPA = 100%). DNA variant repeatability was 100%, except for one BRAF p.V600E instance (NPA = 97.1%). RNA repeatability ranged from 88.9% (ALK fusion) to 100%. Similarly, the ODxET assay showed high clinical concordance with the clinical trial assays for EGFR exon 20 insertions, with a PPA of 97.9%, a NPA of 100%, and an overall percent agreement (OPA) of 98.9%. In the ODxET EGFR exon 20 insertion-positive/clinical trial assay-positive subgroup, response rates were consistent with those observed in the overall sunvozertinib trial population.</p><p><strong>Conclusions: </strong>These findings support the analytical concordance, reproducibility, and clinical utility of the ODxET assay for molecular profiling of FFPE solid tumor samples.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese-Enhanced Magnetic Resonance Imaging: From Translational Research to First-in-Human Trials in Oncology.","authors":"Piotr Remiszewski, Monika A Drabik, Paulina Filipowicz, Marlena Wełniak-Kamińska, Kacper J Piwowarek, Michał Wieteska, Michał Fiedorowicz, Anna M Czarnecka","doi":"10.1007/s40291-026-00874-1","DOIUrl":"https://doi.org/10.1007/s40291-026-00874-1","url":null,"abstract":"<p><p>Manganese-enhanced magnetic resonance imaging (MEMRI) is a functional imaging technique with several potential applications in various research fields. Manganese-enhanced magnetic resonance imaging uses paramagnetic manganese (II) ions (Mn²⁺) as the contrast enhancer, as they accumulate mainly in the cytosol and mitochondria, shorten the longitudinal relaxation time (T₁) and thereby increase signal intensity on T₁-weighted sequences. Most often used in preclinical neuroimaging, MEMRI is also gaining attention in cancer research, providing potentially new insights into tumour biology and treatment response monitoring. The use of MEMRI faces challenges such as the potential toxicity of free manganese and the need for chelation (mangafodipir trisodium, MnPyC3A), careful dosing below ≈25 µmol Mn²⁺/kg and development of new imaging protocols. Ongoing translational research aims to improve the safety profile of manganese agents and optimise imaging strategies. Early clinical studies in neurology and cardiology are exploring MEMRI; clinical oncology use remains investigational and limited. We review preclinical advances and the limited early human experience, outlining safety considerations and the potential, yet unproven, effectiveness of MEMRI in oncology. The present review also contextualises MEMRI within the broader landscape of metal-based precision imaging and neutron capture therapy approaches, including boron neutron capture therapy and gadolinium neutron capture therapy, which represent complementary strategies exploiting the tumour-selective accumulation of specific metal ions. Recent clinical and translational evidence supports the maturation of these approaches: a phase II trial of accelerator-based boron neutron capture therapy with borofalan in head and neck cancer reported acceptable safety, and a systematic review across malignant tumours confirmed favourable efficacy and safety signals for boron neutron capture therapy. Manganese-based nanotheranostics are concurrently emerging as a route to combine magnetic resonance imaging with image-guided therapy.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Diagnostic Models and Biomarker Identification for Type 1 Leptomeningeal Metastasis in Lung Adenocarcinoma Using Olink: Exploratory Cohort Study with Internal Temporal Validation.","authors":"Peng Ding, Qiuchi Chen, Yun Li, Yulan Kui, Zhi Wang, Hongxia Zhou, Bohua Kuang, Lingjuan Chen, Xing Zhang, Minghui Ge, Tiantian Han, Ruiguang Zhang, Fan Tong, Xiaorong Dong","doi":"10.1007/s40291-026-00875-0","DOIUrl":"https://doi.org/10.1007/s40291-026-00875-0","url":null,"abstract":"<p><strong>Background: </strong>To enable early identification of type 1 leptomeningeal metastasis (LM) risk and to identify plasma- and cerebrospinal fluid (CSF)-based biomarkers in lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>Blood and CSF samples were prospectively obtained from patients with advanced LUAD with or without LM. A total of 174 samples were analyzed using the Olink^® Target-96 platform. Two predictive models were established via logistic regression and subjected to internal temporal validation.</p><p><strong>Results: </strong>In total, 88 blood samples and 86 CSF samples were obtained. Seven representative plasma proteins were consistently selected, forming a plasma protein diagnostic model with the area under the curve (AUC, p-training set) of 0.918, a sensitivity of 100%, and a specificity of 73.0%; the AUC in the p-test set was 0.765. A total of 12 representative CSF proteins were selected to establish a CSF protein diagnostic model with an AUC (c-training set) of 0.984, a sensitivity of 96.7%, and a specificity of 96.7%; the AUC in the c-test set was 0.944. In CSF samples, 65 differentially expressed proteins were identified between the LM and nLM groups, and enrichment analysis indicated predominant clustering within inflammatory and immune activation pathways. In addition, tumor necrosis factor receptor superfamily member 9 (TNFRSF9) alone yielded an AUC of 0.960 for discriminating the LM group from the nLM_nBM (brain metastasis) group.</p><p><strong>Conclusions: </strong>A diagnostic model for type 1 LUAD-LM was developed with high accuracy and potential clinical applicability. Moreover, CSF-specific biomarkers have been identified, offering potential candidate targets for the management of LUAD-LM.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Maxwell Kit-Based and NaOH-Based DNA Extraction Incorporated copro-DNA-SjTR1-qPCR Systems: Insights from Detecting Low-Intensity Schistosoma Japonicum Infections.","authors":"Emmanuel John Tabilin, Catherine A Gordon, Mario A Jiz, Eleonor Avenido-Cervantes, Marianette Inobaya, Marcello Otake Sato, Megumi Sato, Yasuhito Sako, Darren J Gray, Mary Lorraine Mationg, Yi Mu, Pengfei Cai","doi":"10.1007/s40291-026-00883-0","DOIUrl":"https://doi.org/10.1007/s40291-026-00883-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Schistosomiasis remains a significant public health issue globally. This study aimed to compare the performance of two molecular diagnostic systems for the detection of low-intensity Schistosoma japonicum infections.</p><p><strong>Methods: </strong>A Maxwell kit-based copro-DNA-SjTR1-qPCR workflow (SjTR1-qPCR-S1) and a NaOH-based copro-DNA-SjTR1-qPCR workflow (SjTR1-qPCR-S2) were compared as integrated systems using faecal samples (n = 554) collected from an S. japonicum-endemic area in Leyte Province, the Philippines. The duplicated Kato-Katz (KK) was performed on three stool samples collected from different days for each participant. The diagnostic performance of KK and the SjTR1-qPCR systems were comprehensively compared with a composite reference where a participant was classified as positive if the KK was positive or any qPCR assay was positive.</p><p><strong>Results: </strong>The KK, SjTR1-qPCR-S1 and SjTR1-qPCR-S2 recorded positivity rates of 25.1% (139/554), 25.5% (141/554) and 29.8% (165/554), respectively. The overall S. japonicum positivity rate was 39.2% (217/554) as determined from the composite reference. Both SjTR1-qPCR systems exhibited excellent sensitivity in individuals with moderate-heavy (eggs per gram ≥ 100) and light (eggs per gram 10-99) infection intensity, with reduced sensitivity observed only in individuals with extremely low egg burden (eggs per gram 1-9). Globally, SjTR1-qPCR-S2 demonstrated significantly higher sensitivity (76.0%) compared with the KK (64.1%) and SjTR1-qPCR-S1 (65.0%) [p < 0.0161 and p = 0.0021, respectively, χ²_m]. For samples positive in both SjTR1-qPCR systems (n = 125), SjTR1-qPCR-S1 showed a significantly higher median Ct value than SjTR1-qPCR-S2 (p < 0.0001, Wilcoxon signed-rank test). Both SjTR1-qPCR systems showed a significant negative correlation between Ct values and faecal egg counts (ρ = - 0.5947 for SjTR1-qPCR-S1, and ρ = - 0.4844 for SjTR1-qPCR-S2, both p < 0.0001). Moderate agreement was observed between both SjTR1-qPCR systems and the KK (κ = 0.560 and κ = 0.512, respectively). However, substantial agreement was found between SjTR1-qPCR-S1 and SjTR1-qPCR-S2 (κ = 0.748). The combined qPCR systems showed a sensitivity of 83.4%.</p><p><strong>Conclusions: </strong>SjTR1-qPCR-S2 is cost effective and less reliant on specialised equipment compared with SjTR1-qPCR-S1. With further optimisation, the SjTR1-qPCR-S2 system can be a powerful and game-changing option for integration into the current surveillance network to support the eradication of schistosomiasis japonica.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gadoquatrane: First Approval.","authors":"Simon Fung","doi":"10.1007/s40291-026-00881-2","DOIUrl":"https://doi.org/10.1007/s40291-026-00881-2","url":null,"abstract":"<p><p>Gadoquatrane (AMBELVIST^®) is a paramagnetic, tetrameric, next-generation, high-relaxivity, low-dose macrocyclic gadolinium-based contrast agent (GBCA) developed by Bayer for use with magnetic resonance imaging (MRI). It received its first global approval for contrast enhancement in MRI of the brain and spinal cord, as well as the other parts of the body (trunk and extremities) in March 2026 in Japan. Subsequently, it was approved for use with MRI to detect and visualize lesions with abnormal vascularity in the CNS (brain, spine, and associated tissues) and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system) in June 2026 in the USA. It has also been approved in adults and children of all ages including neonates for contrast enhancement in MRI to detect and visualise known or suspected pathology in the CNS (brain, spine, and associated tissues) and the body (head and neck, thorax including breast, abdomen, pelvis, and extremities) in July 2026 in Canada. Gadoquatrane has been submitted for regulatory review in the EU and China. This article summarizes the milestones in the development of gadoquatrane leading to its approval.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Reference Data in the Molecular Diagnosis of Pathogenic CAPN3 Variants: Contextual Evidence and Interpretive Limits.","authors":"Meghan H Carr, Ehab Y Harahsheh, Shaymaa Shurrab, Bukola A Olarewaju, Mayowa A Osundiji","doi":"10.1007/s40291-026-00880-3","DOIUrl":"https://doi.org/10.1007/s40291-026-00880-3","url":null,"abstract":"<p><strong>Background and objective: </strong>Pathogenic variants in CAPN3 cause calpainopathy, but the diagnostic use of population-scale sequence data remains challenging, because allele frequency, inheritance assumptions, and variant classification do not directly predict clinical disease expression. This study evaluated how population reference data can inform interpretation of pathogenic CAPN3 variants in a molecular diagnostic context.</p><p><strong>Methods: </strong>We analyzed CAPN3 variants in gnomAD v4.1.0, applied ClinVar-supported American College of Medical Genetics and Genomics (ACMG)/ Association for Molecular Pathology (AMP) categorization to identify pathogenic and likely pathogenic variants, mapped classified variants across annotated protein domains, and used cumulative allele frequency to contextualize expected disease burden under recessive and dominant inheritance models.</p><p><strong>Results: </strong>A total of 5185 CAPN3 variants were identified, of which, 399 were classified as pathogenic or likely pathogenic. These variants were distributed broadly across the gene and protein, and included missense, nonsense, and frameshift changes, supporting a heterogeneous diagnostic landscape rather than a single recurrent hotspot. Using a cumulative pathogenic/likely pathogenic allele frequency of 0.0059, the modeled disease burden was approximately 35 per 1,000,000 under an autosomal recessive framework and 17.5 per 1000 under a dominant framework.</p><p><strong>Conclusions: </strong>The recessive estimate is more consistent with current clinical understanding of calpainopathy, whereas the dominant estimate likely overstates manifest disease, because penetrance, phase, and phenotype are not captured by aggregate reference-dataset variation. Population reference data can therefore strengthen molecular diagnostic interpretation of rare disease, but only when integrated with inheritance-aware, phenotype-informed clinical assessment.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orca-T: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40291-026-00882-1","DOIUrl":"https://doi.org/10.1007/s40291-026-00882-1","url":null,"abstract":"<p><p>Allogeneic regulatory T cell immunotherapy with haematopoietic stem and progenitor cells (HSPC) and T cells-vldq, hereafter referred to as Orca-T (TREGZI^™), has been developed by Orca Bio under license from Stanford University for the prevention of chronic graft-versus-host disease (cGVHD). On 30 June 2026, Orca-T received its first approval in the USA for use in matched donor haematopoietic stem cell transplantation (HSCT) with myeloablative preparative regimen, for haematopoietic and immunologic reconstitution and to improve cGVHD-free survival, in the treatment of adults with haematological malignancies. This article summarizes the milestones in the development of Orca-T leading to this first approval for the prevention of cGVHD.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Ex Vivo Visualization of Laryngeal Tumors Using a Sprayable pH-Activatable Fluorophore.","authors":"Daan G J Linders, Sebastiaan W R Dalmeijer, Bo E Zweedijk, Hamed Abbasi, Danielle Boldewijn, Sjors A Koppes, Bernd Kremer, Jacobus Burggraaf, Denise E Hilling, Joost R van der Vorst, Jinhui Ser, Satoshi Kashiwagi, Maged Henary, Jeroen C Jansen, Alexander L Vahrmeijer, Hak Soo Choi, Stijn Keereweer","doi":"10.1007/s40291-026-00878-x","DOIUrl":"https://doi.org/10.1007/s40291-026-00878-x","url":null,"abstract":"<p><strong>Introduction: </strong>Achieving clear resection margins (> 5 mm) is critical during laryngeal and hypopharyngeal tumor resection, as positive margins are associated with reduced disease-specific survival. Near-infrared (NIR) fluorescence imaging has emerged as a valuable tool for intraoperative margin assessment by enabling real-time visualization of residual tumor tissue. However, current fluorescent contrast agents rely on intravenous administration, often requiring dosing hours to days before surgery. Also, targeting tumor-specific biomarkers with heterogeneous expression limits applicability. To address these limitations, we evaluated the feasibility of a topically applied pH-activatable fluorophore (PH10), which selectively fluoresces under acidic conditions. This ex vivo proof-of-concept study investigates whether topical PH10 can visualize laryngeal and hypopharyngeal tumors.</p><p><strong>Methods: </strong>Freshly resected laryngeal and hypopharyngeal squamous cell carcinoma (SCC) specimens were obtained from ten patients and topically sprayed with PH10 immediately after surgery. Following a 2-min incubation period, NIR fluorescence images were acquired before and after three sequential saline washes. Fluorescence intensity was quantified as the tumor-to-background ratio (TBR); tumor localization was confirmed on histopathology.</p><p><strong>Results: </strong>Laryngeal tumors demonstrated tumor-specific fluorescence upon PH10 application, with significantly higher signal intensity in tumor tissue compared to adjacent normal mucosa (P < 0.05). The median TBR after the first wash was 2.3 (interquartile range 1.7-3.0), exceeding the clinically relevant threshold of 1.5 in seven of seven laryngeal SCC cases; however, this threshold was not reached in either of the two hypopharyngeal carcinoma cases included.</p><p><strong>Conclusions: </strong>This proof-of-concept study suggests that PH10, a sprayable pH-activatable fluorophore, can enable rapid and high-contrast visualization of laryngeal tumors, although this was not observed in the small number of hypopharyngeal cases evaluated. Given its topical application and rapid activation, PH10 may hold promise for intraoperative margin assessment, yet these preliminary findings, based on a small and heterogeneous sample, require validation in larger cohorts, including direct correlation with deep resection margins, before clinical utility can be established.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyloid-β PET Radioligands in Alzheimer's Disease: From Plaque Detection to Biomarker-Guided Patient Stratification and Therapeutic Monitoring.","authors":"Simone Lista, Luca Filippi, Enzo Emanuele, Susana López-Ortiz, Giusy Ylenia Cisale, Piercarlo Minoretti, Francesco Garaci, Alejandro Santos-Lozano","doi":"10.1007/s40291-026-00879-w","DOIUrl":"https://doi.org/10.1007/s40291-026-00879-w","url":null,"abstract":"<p><p>Amyloid-β (Aβ) positron emission tomography allows direct in vivo visualization of insoluble fibrillar Aβ deposition and has been used to detect Alzheimer's disease pathology across the clinical continuum, from preclinical stages to overt dementia. Aβ tracers progressed from the prototypical [¹¹C]Pittsburgh Compound-B ([¹¹C]PiB), which is limited by [¹¹C] half-life, to [¹⁸F]-labeled agents, including [¹⁸F]Florbetapir, [¹⁸F]Florbetaben, and [¹⁸F]Flutemetamol, which allowed centralized production and wide clinical use, with [¹⁸F]NAV4694 currently in development. In this narrative review, we sought to examine the principal Aβ positron emission tomography radioligands and their methodological framework, including visual reads, the standardized uptake value ratio, and the Centiloid scale, which harmonized quantitative output across tracers, scanners, and protocols and may enable cross-site comparison in multicenter studies and disease-modifying trials. The regulatory approval of lecanemab and donanemab has recently expanded the clinical use of Aβ positron emission tomography. Beyond diagnostic confirmation, the modality can currently confirm eligibility for anti-Aβ therapy, enrich trial populations, monitor target engagement through serial Centiloid measurements, and inform treatment discontinuation at predefined clearance thresholds. However, significant limitations remain, including the imperfect correlation between a high Aβ plaque burden and clinical cognitive decline that constrains its standalone diagnostic utility, tracer-specific variability, restricted accessibility, and the inability of fibril-targeted tracers to image the soluble oligomeric species most directly engaged by anti-Aβ antibodies. Probes for non-fibrillar species and computational tools for assisted interpretation are likely to shape the field in the near future.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging Biomarker Testing to Biomarker-Driven Targeted Therapy: Real-World ESR1 Mutation Testing Patterns and Prevalence in ER+, HER2- Metastatic Breast Cancer.","authors":"Chi-Yin Liao, Jincy John, Precious Anyanwu, Manali A Bhave, Francois-Clement Bidard, Tyler Marquart, Francisco Sapunar, Aarti Chawla, Lindsay A Williams","doi":"10.1007/s40291-026-00876-z","DOIUrl":"https://doi.org/10.1007/s40291-026-00876-z","url":null,"abstract":"<p><strong>Background: </strong>The estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) treatment landscape continues to evolve with targeted therapy development. Estrogen receptor 1 (ESR1) testing is recommended at recurrence or each progression event to identify patients for effective therapies. However, there is limited information on testing and mutation patterns in the real world that can inform patient identification in the clinic.</p><p><strong>Methods: </strong>A retrospective observational study among patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative MBC who initiated first line (1L) therapy with aromatase inhibitors or selective estrogen receptor degraders ± CDK4/6 inhibitors from 1 January, 2020 to 31 March, 2025, using the Flatiron Health Research Database was conducted. ESR1 testing and mutation positivity rates at 1L to third line initiation, stratified by endocrine-resistant, 1L endocrine-sensitive, and endocrine-sensitive/de novo MBC were descriptively reported.</p><p><strong>Results: </strong>Overall testing rates varied across subgroups, with one or more ESR1 test per patient in 61.2% of patients with endocrine-resistant MBC (n = 2152), 50.5% in patients with 1L endocrine-sensitive MBC (n = 827), and 43.1% in patients with endocrine-sensitive/de novo MBC (n = 5772). Testing rates at 1L initiation were 36.2% in endocrine-resistant MBC and 19.6% in endocrine-sensitive/de novo MBC. Testing rates were approximately 32% at second line and 25% at third line across subgroups. ESR1 mutation positivity (ESR1m+) rates varied by subgroup at 1L initiation and were highest among patients with endocrine-resistant MBC (24.7%), followed by patients with 1L endocrine-sensitive MBC (6.9%) and patients with endocrine-sensitive/de novo MBC (2.1%). All groups had ESR1m+ rates around 30% at second line initiation and 40% at third line initiation. In an exploratory analysis, ~ 60% of ESR1 tests during 1L were conducted in tissue and ~ 40% in blood.</p><p><strong>Conclusions: </strong>In this population, real-world ESR1 testing rates were low. One in four patients with endocrine-resistant MBC were ESR1m+ at 1L initiation, ~ 30% were ESR1m+ at second line across subgroups, and ~ 40% were ESR1m+ at third line across subgroups. More blood-based testing at recurrence and progression is recommended in the real world to align with guideline recommendations as ESR1m detection is more sensitive in blood than in tissue.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}