Molecular Diagnosis & Therapy最新文献

{"title":"Amino Acid Transporters in Glioblastoma: Implications for Diagnosis, Disease Monitoring, Therapeutic Targeting, and Drug Delivery.","authors":"Emanuella M Brito, Emma M Baker, Nicholas M Ahye, Bryan A Lieber, Sajini Hettiarachchi, Maria J Moreno Hollweg, Sabrin B Safar, Steven Vanni, Regina M Graham","doi":"10.1007/s40291-025-00810-9","DOIUrl":"https://doi.org/10.1007/s40291-025-00810-9","url":null,"abstract":"<p><p>Glioblastoma (GBM) is an aggressive primary brain tumor with a median survival of 14-15 months even with standard multimodality treatments. The effectiveness of surgical resection, chemotherapy, and radiation therapy are limited by resistance mechanisms including tumor heterogeneity, immunosuppression, presence of stem-like cells, and inhibited drug delivery due to the blood-brain barrier (BBB). The BBB is composed of endothelial cells with tight junctions and selective transport systems, which prevent drug delivery to the tumor at therapeutic levels. Amino acid (AA) transporters have emerged as promising therapeutic targets for overcoming these limitations and enhancing GBM treatment. This review highlights the role of AA transporters in GBM, emphasizing their potential in enhancing targeted therapy, diagnosis, and disease monitoring. We summarize and discuss the 22 AA transporters which are upregulated in GBM, as well as those that demonstrate prognostic correlation. Among these, LAT1 (SLC7A5) has garnered the most attention for its role in drug delivery and imaging, while other transporters exhibit potential as diagnostic and therapeutic targets. Furthermore, nanoparticle technology has emerged as an innovative strategy to enhance targeted therapy through AA transporters. They can enable extended drug circulation, enhanced BBB penetration, and target-specific localization, offering synergistic therapeutic effects. This review emphasizes the importance of AA transporters as multifaceted tools for improving GBM treatment outcomes and the potential of combining AA transporter-targeted therapies with emerging technologies to address the limitations of current GBM management strategies.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975890","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":"Human Papillomavirus Type and Viral Load in Relation to Circulating Cell-Free Tumour HPV DNA Level and Survival in Cervical Cancer.","authors":"Kristina Hellman, Mark Zupancic, Cecilia Jylhä, Emma Tham, Lars Sivars","doi":"10.1007/s40291-025-00809-2","DOIUrl":"https://doi.org/10.1007/s40291-025-00809-2","url":null,"abstract":"<p><strong>Background and objective: </strong>Human papillomavirus (HPV) is the cause of most cervical cancers and is released as circulating cell-free tumour HPV DNA (ctHPV DNA) into circulation. Earlier studies have indicated that ctHPV DNA is a promising biomarker for analysing treatment response and for recurrence surveillance. However, factors influencing the release of ctHPV DNA, including HPV type and HPV viral load, have not been extensively studied and additional biomarkers for prognosis are needed. Therefore, here we analysed ctHPV DNA, HPV type and viral load in relation to each other and to progression-free survival in patients with locally advanced or advanced cervical cancer.</p><p><strong>Methods: </strong>Pre-treatment biopsies and blood samples were collected from patients diagnosed with cervical cancer (Federation of Gynecology and Obstetrics [FIGO] stage IB-IV). One hundred and seventeen patients with HPV-positive tumours were included. Human papillomavirus type-specific, droplet digital polymerase chain reaction (ddPCR) assays were used to analyse previously genotyped biopsies for the viral load. Pre-treatment plasma from 92/117 patients were available and analysed for ctHPV DNA and total cell-free DNA levels. Results were related to patient and tumour characteristics and progression-free survival. Patients were grouped based on HPV species where alpha-9-species (including HPV16) and alpha-7-species (including HPV 18) constituted the majority of cases.</p><p><strong>Results: </strong>Cell-free tumour HPV DNA was found in 83/92 (90.2%) of pre-treatment plasma samples. Higher biopsy viral load was significantly related to a higher ctHPV DNA level. Higher stage and larger primary tumour size were also associated with higher ctHPV DNA level. Alpha-9 species, including HPV16, had a significantly higher viral load (16×), a higher ctHPV DNA level (17×), and a higher detection rate in plasma than alpha-7 species, including HPV18. Alpha-9 species also had significantly better progression-free survival than alpha-7 species. Additional factors leading to better progression-free survival included a lower stage, a lower total cell-free DNA level, a viral load in the 90th percentile and, in the high-risk cervical cancer group, a higher pre-treatment ctHPV DNA level.</p><p><strong>Conclusions: </strong>Cell-free tumour HPV DNA, HPV type and viral load are promising biomarkers in cervical cancer. The lower sensitivity for ctHPV DNA detection for alpha-7 species, including HPV18, needs to be considered in future studies on ctHPV DNA, especially if used as a marker for relapse during surveillance when ctHPV DNA levels are very low.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862615","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":"Clinical, Genetic, Morphological and Functional Correlations in a Large Series of Patients with Primary Ciliary Dyskinesia: A Heterogeneous Disease with a Controversial Diagnosis.","authors":"Lidón Carretero-Vilarroig, Rosana Blanco-Máñez, Noelia Muñoz-Fernández, Isabel Ibáñez, Alba Berzal-Serrano, Ana Reula, Belén García-Bohórquez, Elena Aller, Gema García-García, Jose M Millán, Miguel Armengot-Carceller, Teresa Jaijo","doi":"10.1007/s40291-025-00801-w","DOIUrl":"https://doi.org/10.1007/s40291-025-00801-w","url":null,"abstract":"<p><strong>Background and objective: </strong>Primary ciliary dyskinesia (PCD) is a rare genetic condition characterised by abnormal ciliary motility, primarily affecting the respiratory tract. Despite its clinical significance, there is currently no gold standard for PCD diagnosis. This study aims to address this diagnostic challenge by evaluating a comprehensive approach in a large cohort of patients with suspected PCD.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 128 patients with suspected PCD at a specialised clinical reference unit. A thorough anamnesis was performed, followed by a triad of diagnostic tests: (i) a high-speed video analysis of ciliary beat pattern; (ii) transmission electron microscopy for ciliary ultrastructure examination; and (iii) a genetic analysis, primarily through clinical exome sequencing. Correlations between the clinical, morphological and genetic findings were studied. Functional assays on RNA were performed to assess new splicing variants. Pearson's chi-square test was used to compare categorical variables and comparisons of means were performed using the Student's t-test.</p><p><strong>Results: </strong>A definitive PCD diagnosis was established in 72% of the studied patients. Notably, only 58% of the diagnosed cases showed positive results across all three diagnostic tests. Patients with immotile cilia have a higher frequency of neonatal respiratory distress and had a higher likelihood of receiving a genetic diagnosis. A high-speed video analysis was altered in 116 patients, 53 of them with immotile cilia. A transmission electron microscopy revealed ultrastructural alterations in 67 patients, with class 1 defects being more common. DNAH5, RSPH1 and DNAH11 were the most represented genes among the 18 causal genes found. Among the 71 causal genetic variants found, we highlight the overrepresentation of the c.85G>T in RSPH1 and describe the aberrant effect on RNA of the splicing variants DNAH11:c.11497-6T>G, DNAH9:c.2596-2dup, CCDC40:c.2597A>G and CCDC40:c.2832G>A. Finally, we describe a severe phenotype associated with the RSPH1 gene, contrary to previously reported data.</p><p><strong>Conclusions: </strong>This comprehensive analysis of a large cohort of patients with PCD underscores the challenges in achieving a definitive diagnosis and emphasises the need for a multi-faceted diagnostic approach. This study enhances our understanding of this rare condition, including the identification of new splicing variants and an unexpected severe phenotype associated with RSPH1, challenging previous assumptions about genotype-phenotype correlations in PCD.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754955","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":"Long-Range PCR and Nanopore Sequencing Enables High-Throughput Detection of TCF4 Trinucleotide Repeat Expansions in Fuchs Endothelial Corneal Dystrophy.","authors":"Bushra Alayed, Salina Siddiqui, Seema Anand, Chris F Inglehearn, Christopher M Watson, Manir Ali","doi":"10.1007/s40291-025-00803-8","DOIUrl":"https://doi.org/10.1007/s40291-025-00803-8","url":null,"abstract":"<p><strong>Introduction: </strong>Trinucleotide repeat expansion in CTG18.1, in intron 2 of TCF4 (MIM *602272, #613267), is the main cause of Fuchs endothelial corneal dystrophy (FECD), accounting for around 75% of cases in Caucasians. CTG18.1 repeat expansion has typically been detected in peripheral blood genomic DNA by Southern blotting or short tandem repeat polymerase chain reaction (STR-PCR) combined with triplet-repeat primed PCR (TP-PCR) if needed. However both methods estimate the size of the expanded repeat relative to a size standard, and the former requires microgram amounts of DNA. To support the development of therapies, a high-throughput screening approach for repeat expansions in FECD is required. Here, we present a sensitive assay using long-range PCR and nanopore sequencing of genomic DNA to accurately resolve the CTG18.1 repeat.</p><p><strong>Methods: </strong>The CTG18.1 locus was analysed in genomic DNA from peripheral blood leukocytes by two different methods, and results were compared. The first approach used STR-PCR and capillary electrophoresis, followed by confirmatory testing of apparent homozygotes by TP-PCR. The second used long-range PCR, library preparation and long-read sequencing on an Oxford Nanopore Technologies MinION, with resolution of repeat length using the STRique algorithm.</p><p><strong>Results: </strong>CTG18.1 expansion was screened for in 119 patients with FECD and 83 controls, by STR/TP-PCR genotyping and, independently, by long-range PCR/long-read nanopore sequencing. Both methods gave comparable results, but the latter was also able to measure repeat length. A total of 73.1% of FECD cases (87/119) and 1.2% of age-matched controls (1/83) had at least one CTG18.1 expansion that was ≥ 50 repeats. The expanded CTG18.1 allele was inherited across multiple generations in four larger families, in a manner consistent with causing a dominant phenotype, revealing that some younger family members may be at risk. The G allele of SNP rs599550, ~1kb away from the expansion, is linked (in cis) with expanded alleles in 80.8% of FECD alleles with an expansion, compared with 12.5% in FECD alleles in cases without an expansion and 14.6% in Europeans.</p><p><strong>Discussion: </strong>We demonstrate that long-range PCR and long-read nanopore sequencing is a sensitive method requiring only nanograms of DNA, which can be scaled up for high-throughput detection and accurate sizing of CTG18.1 in peripheral blood DNA. The SNP, rs599550, is in linkage disequilibrium with the expansion and physically closer than rs613872, previously used in FECD association studies, making it better for use in diagnostic or association studies.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734951","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":"Salivary Biomarkers in Periodontal Disease: Revolutionizing Early Detection and Precision Dentistry.","authors":"Seyed Ebrahim Alavi, Lavanya A Sharma, Ajay Sharma, Hasan Ebrahimi Shahmabadi","doi":"10.1007/s40291-025-00799-1","DOIUrl":"https://doi.org/10.1007/s40291-025-00799-1","url":null,"abstract":"<p><p>This review explores the transformative potential of salivary biomarkers in revolutionizing periodontal disease diagnostics and management through a non-invasive real-time analysis. A comprehensive literature search was performed using databases such as PubMed, Scopus, and Google Scholar, from inception to March 2025 employing keywords such as \"salivary biomarkers,\" \"periodontal disease,\" \"biosensor,\" \"precision dentistry,\" and \"pro-inflammatory cytokines.\" Saliva, rich in inflammatory cytokines (e.g., interleukin-1β, interleukin-6, tumor necrosis factor-α), enzymatic markers (e.g., matrix metalloproteinase-8, matrix metalloproteinase-9), microbial DNA, oxidative stress indicators, and emerging biomarkers such as exosomes and microRNAs, offers a dynamic medium for early disease detection, risk stratification, and therapeutic monitoring. Technological advancements, including biosensors, lab-on-a-chip systems, and artificial intelligence-driven analytics, enable precise point-of-care applications that align with precision dentistry paradigms. These innovations facilitate personalized interventions by identifying subclinical inflammation, tracking disease progression, and tailoring treatments to individual molecular profiles. However, challenges such as biomarker variability, standardization of collection protocols, cost, and regulatory hurdles impede clinical translation. Future directions emphasize interdisciplinary collaboration, expanded biomarker panels, and rigorous clinical trials to validate diagnostic accuracy and scalability. By bridging gaps between laboratory research and clinical practice, salivary diagnostics promise to shift periodontal disease management from reactive to proactive care, enhancing patient outcomes and reducing systemic disease risks. This review underscores saliva's pivotal role in advancing oral health diagnostics while advocating for optimized methodologies to realize its full potential in precision dentistry.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668867","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":"Cell-Free HPV-DNA in Screening, Diagnosis, Prognosis, and Treatment Response Monitoring of Cervical Cancer.","authors":"Nayara Nascimento Toledo Silva, Ana Carolina Silva Santos, Isadora Oliveira Ansaloni Pereira, Glenda Nicioli da Silva, Angélica Alves Lima","doi":"10.1007/s40291-025-00790-w","DOIUrl":"10.1007/s40291-025-00790-w","url":null,"abstract":"<p><p>Persistent infection with high-risk human papillomavirus (HPV) is a significant factor in cervical cancer (CC) development. Although CC screening programs have reduced the incidence of this neoplasm, the number of deaths remains high, especially in developing countries: CC remains the fourth most common neoplasm in the female population globally. Currently, an HPV test has been replacing cytological analysis because it is a more sensitive screening method. However, the collection of gynecological material is still necessary, which can be a barrier to adherence to testing in the target population. Host cells presenting with a viral infection release fragments of their DNA into circulation, known as cell-free DNA (cfDNA); this allows detection through venous puncture, a routine procedure in clinical laboratories. Thus, the objective of this review was to evaluate the role of cfDNA of HPV (cfHPV-DNA) as an alternative tool for CC screening, diagnosis, prognosis, and treatment response monitoring. Furthermore, the development of sensitive methods, such as droplet digital PCR (ddPCR) and next-generation sequencing (NGS), have proven useful in identifying tumor markers for CC. The specificity of the primers, the size of the target DNA fragments, and variables such as sample type and volume, in addition to the cfDNA extraction kit used, can influence the results of cfHPV-DNA detection. Although the detection of cfHPV-DNA in plasma and serum of patients with CC is feasible, there were conflicting results regarding cfHPV-DNA detection in the blood circulation of patients with premalignant lesions. On the other hand, when CC is already established, the detection and quantification of cfHPV-DNA have shown potential as a biomarker for tumor staging, prognosis definition, and treatment response monitoring.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"483-497"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217395","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":"Recurrent and Novel Pathogenic Variants in Genes Involved with Hearing Loss in the Pakistani Population.","authors":"Madiha Shadab, Afif Ben-Mahmoud, Luis Nicolás Martínez Völter, Ansar Ahmed Abbasi, Bonsu Ku, Ahsan Ejaz, Zahid Latif, Vijay Gupta, Daniel Owrang, Mi-Hyeon Jang, Zijin Zhang, Rahema Mohammad, Henry Houlden, Hyung-Goo Kim, Barbara Vona","doi":"10.1007/s40291-025-00782-w","DOIUrl":"10.1007/s40291-025-00782-w","url":null,"abstract":"<p><strong>Background: </strong>Molecular diagnostic rates for hereditary hearing loss vary by genetic ancestry, highlighting the importance of population-specific studies. In Pakistan, where consanguineous marriages are prevalent, genetic research has identified many autosomal recessive genes, advancing understanding of rare and novel hearing loss mechanisms. This study aimed to identify pathogenic genetic variants in 31 families from Azad Kashmir, Pakistan, presenting non-syndromic hearing loss.</p><p><strong>Methods: </strong>We conducted exome sequencing and bioinformatics analysis, and targeted gene sequencing on 31 Pakistani families with hearing loss.</p><p><strong>Results: </strong>We identified ten pathogenic, three likely pathogenic variants, and one variant of uncertain significance, comprising six nonsense, four missense, three frameshift, and one deep intronic variant, across ten hearing loss-associated genes (MYO15A, GJB2, SLC26A4, TMC1, HGF, TMIE, SLC19A2, KCNE1, ILDR, PCDH15 and MYO6) in 25 families. The overall diagnostic rate, including families with pathogenic and likely pathogenic variants, was 77.4%. GJB2 was the most frequently affected gene, identified in seven families. Thirteen out of 14 identified variants were homozygous. Notably, we identified two novel variants: MYO15A (NM_016239.4, DFNB3) c.870C>G, p.(Tyr290*) and MYO6 (NM_016239.4, DFNB37) c.3465del, p.(Pro1156Leufs*9). Additionally, we identified c.10475dupA, p.(Leu3493Alafs*25) in MYO15A (NM_016239.4, DFNB3) and c.617T>A, p.(Leu206*) in SLC26A4 (NM_000441.2, DFNB4), previously documented in ClinVar but unpublished. We also propose SLC19A2 as a candidate gene presenting as non-syndromic hearing loss, despite its association with thiamine-responsive megaloblastic anemia syndrome.</p><p><strong>Conclusion: </strong>Our work expands the genotypic and phenotypic spectrum of hearing loss by emphasizing the importance of investigating under-represented groups to identify unique genetic variants and clinical characteristics. Such efforts deepen understanding of genetic diversity in under-represented populations to improve diagnosis and treatment strategies.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"519-537"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Dynamics as a Precision Therapy: A Perspective on Epileptic Encephalopathies.","authors":"Raffaele Falsaperla, Vincenzo Sortino, Federica Maria Sipala, Simone Ronsisvalle, Piero Pavone","doi":"10.1007/s40291-025-00780-y","DOIUrl":"10.1007/s40291-025-00780-y","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"425-429"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056328","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":"Research Progress on Signal Conversion Based on Aptamer Combined CRISPR/Cas System in Biosensors.","authors":"Yihua Wang, Hui Li, Sijian Luo, Min Zhong, Jinbo Liu, Baolin Li","doi":"10.1007/s40291-025-00785-7","DOIUrl":"10.1007/s40291-025-00785-7","url":null,"abstract":"<p><p>The CRISPR/Cas system has been extensively used in the fields of biology, food safety, and environmental monitoring. This is in part because its can to be used in combination with isothermal amplification-mediated signal amplification technology along with its extraordinary trans-cleavage ability, which has initiated a new era of biosensing applications. The popularity of functional nucleic acids has enabled aptamers to convert non-nucleic acid substances into programmable nucleic acid sequences through methods such as direct detection, lock activation, sandwich design, induction of conformations, and split aptamers. Additionally, CRISPR/Cas systems have been extended beyond nucleic acid detection to include ions, small molecules, proteins, cells, bacteria, viruses, and other non-nucleic acid-based target substances. This article provides a brief overview of the mechanisms of action of four Cas proteins, the generation of aptamers, and their combined applications. Moreover, we focus on the research progress of biosensors based on aptamer-based signal conversion combined with the CRISPR/Cas system.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"499-518"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327538","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":"FAPI-Targeted Molecular Imaging: Transforming Insights into Post-Ischemic Myocardial Remodeling?","authors":"Luca Filippi, Marco Alfonso Perrone, Orazio Schillaci","doi":"10.1007/s40291-025-00778-6","DOIUrl":"10.1007/s40291-025-00778-6","url":null,"abstract":"<p><p>Post-ischemic myocardial remodeling significantly impacts clinical outcomes after acute myocardial infarction (MI), involving structural and functional changes such as ventricular dilation, infarct wall thinning, and fibrosis development. These processes, driven by inflammatory cascades, neurohormonal activation, and extracellular matrix remodeling, result in impaired cardiac output and an increased risk of heart failure. Imaging with fibroblast activation protein inhibitors (FAPI) has emerged as a promising non-invasive tool for assessing myocardial fibrosis via positron emission tomography (PET) or single-photon emission computed tomography (SPECT), targeting activated fibroblasts; the mediators of reparative and fibrotic processes. This innovative approach enables precise visualization and quantification of fibrosis dynamics, surpassing traditional imaging modalities. Preclinical studies using [⁶⁸Ga]Ga-FAPI PET/computed tomography (CT) demonstrated the tracer's specificity for fibroblast activation and its peak uptake in the infarct border zone at day 6 post-MI. These findings, corroborated by histology and autoradiography, highlight its potential for tracking reparative fibrosis. Clinical translation of FAPI imaging was recently achieved with [⁶⁸Ga]Ga-FAPI-46 PET/magnetic resonance imaging (MRI), showing persistent fibroblast activity beyond infarct zones and strong correlations with myocardial injury markers. Complementary research on [^99mTc]Tc-HFAPi SPECT imaging in patients post-MI established its predictive value for left ventricular remodeling, emphasizing its cost-effectiveness and accessibility compared with PET. These advancements underscore FAPI-based imaging's potential to transform risk stratification and therapeutic guidance in post-MI care.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"435-442"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}