Molecular Imaging and Biology最新文献

{"title":"Neurotoxin-Derived Optical Probes for Elucidating Molecular and Developmental Biology of Neurons and Synaptic Connections : Toxin-Derived Optical Probes for Neuroimaging.","authors":"Rohini Bijjam, Susan Shorter, Alison M Bratt, Valerie B O'Leary, Vasilis Ntziachristos, Saak Victor Ovsepian","doi":"10.1007/s11307-024-01954-6","DOIUrl":"10.1007/s11307-024-01954-6","url":null,"abstract":"<p><p>Botulinum neurotoxins (BoNTs) and tetanus toxin (TeTX) are the deadliest biological substances that cause botulism and tetanus, respectively. Their astonishing potency and capacity to enter neurons and interfere with neurotransmitter release at presynaptic terminals have attracted much interest in experimental neurobiology and clinical research. Fused with reporter proteins or labelled with fluorophores, BoNTs and TeTX and their non-toxic fragments also offer remarkable opportunities to visualize cellular processes and functions in neurons and synaptic connections. This study presents the state-of-the-art optical probes derived from BoNTs and TeTX and discusses their applications in molecular and synaptic biology and neurodevelopmental research. It reviews the principles of the design and production of probes, revisits their applications with advantages and limitations and considers prospects for future improvements. The versatile characteristics of discussed probes and reporters make them an integral part of the expanding toolkit for molecular neuroimaging, promoting the discovery process in neurobiology and translational neurosciences.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"912-925"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical Evaluation of Cathepsin B, L, and S Expression in Breast Cancer Patients.","authors":"Daan G J Linders, Okker D Bijlstra, Laura C Fallert, N Geeske Dekker-Ensink, Taryn L March, Martin Pool, Ethan Walker, Brian Straight, James P Basilion, Matthew Bogyo, Jacobus Burggraaf, Denise E Hilling, Alexander L Vahrmeijer, Peter J K Kuppen, A Stijn L P Crobach","doi":"10.1007/s11307-024-01955-5","DOIUrl":"10.1007/s11307-024-01955-5","url":null,"abstract":"<p><strong>Purpose: </strong>Cysteine cathepsins are proteases that play a role in normal cellular physiology and neoplastic transformation. Elevated expression and enzymatic activity of cathepsins in breast cancer (BCa) indicates their potential as a target for tumor imaging. In particular cathepsin B (CTSB), L (CTSL), and S (CTSS) are used as targets for near-infrared (NIR) fluorescence imaging (FI), a technique that allows real-time intraoperative tumor visualization and resection margin assessment. Therefore, this immunohistochemical study explores CTSB, CTSL, and CTSS expression levels in a large breast cancer patient cohort, to investigate in which BCa patients the use of cathepsin-targeted NIR FI may have added value.</p><p><strong>Procedures: </strong>Protein expression was analyzed in tumor tissue microarrays (TMA) of BCa patients using immunohistochemistry and quantified as a total immunostaining score (TIS), ranging from 0-12. In total, the tissues of 557 BCa patients were included in the TMA.</p><p><strong>Results: </strong>CTSB, CTSL, and CTSS were successfully scored in respectively 340, 373 and 252 tumors. All tumors showed CTSB, CTSL, and/or CTSS expression to some extent (TIS > 0). CTSB, CTSL, and CTSS expression was scored as high (TIS > 6) in respectively 28%, 80%, and 18% of tumors. In 89% of the tumors scored for all three cathepsins, the expression level of one or more of these proteases was scored as high (TIS > 6). Tumors showed significantly higher cathepsin expression levels with advancing Bloom-Richardson grade (p < 0.05). Cathepsin expression was highest in estrogen receptor (ER)-negative, human epidermal growth factor receptor 2(HER2)-positive and triple-negative (TN) tumors. There was no significant difference in cathepsin expression between tumors that were treated with neoadjuvant systemic therapy and tumors that were not.</p><p><strong>Conclusions: </strong>The expression of at least one of the cysteine cathepsins B, L and S in all breast tumor tissues tested suggests that cathepsin-activatable imaging agents with broad reactivity for these three proteases will likely be effective in the vast majority of breast cancer patients, regardless of molecular subtype and treatment status. Patients with high grade ER-negative, HER2-positive, or TN tumors might show higher imaging signals.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"1057-1067"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Comparison of [¹⁸F]FDG and [¹⁸F]AIF-FAPI-74 PET/CT in the Evaluation of Potentially Resectable Pancreatic Ductal Adenocarcinoma.","authors":"Won-Gun Yun, Joonhyung Gil, Hongyoon Choi, Youngmin Han, Hye-Sol Jung, Young Jae Cho, Minseok Suh, Wooil Kwon, Yun-Sang Lee, Gi Jeong Cheon, Jin-Young Jang","doi":"10.1007/s11307-024-01950-w","DOIUrl":"10.1007/s11307-024-01950-w","url":null,"abstract":"<p><strong>Purpose: </strong>Accurate clinical staging of potentially resectable pancreatic ductal adenocarcinoma (PDAC) is critical for establishing optimal treatment strategies. While the efficacy of fluorine-18-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) in clinical staging is unclear, PET/CT detecting fibroblast-activation protein (FAP) expression has recently received considerable attention for detecting various tumors, including PDAC, with high sensitivity. We explored the efficacy of [¹⁸F]FDG and [¹⁸F]AIF-FAPI-74 PET/CT in the initial evaluation of potentially resectable PDAC.</p><p><strong>Procedures: </strong>Between 2021 and 2022, twenty participants with newly diagnosed potentially resectable PDAC were enrolled. After the initial evaluation with pancreatic CT, [¹⁸F]FDG PET/CT, and [¹⁸F]AIF-FAPI-74 PET/CT, treatment strategies were determined considering the participant's general status, clinical staging, and resectability. Pathological information from the surgical specimens was only available in 17 participants who underwent curative-intent surgery. Head-to-head comparisons of quantitative radiotracer uptake and diagnostic performance were performed among imaging modalities.</p><p><strong>Results: </strong>[¹⁸F]AIF-FAPI-74 PET/CT showed a significantly higher maximum standardized uptake value than [¹⁸F]FDG PET/CT did in evaluating primary pancreatic lesions (median [interquartile range]; 12.6 [10.7-13.7] vs. 6.3 [4.8-9.2]; P < 0.001). In contrast, [¹⁸F]AIF-FAPI-74 PET/CT showed a significantly lower mean standardized uptake value than [¹⁸F]FDG PET/CT did in evaluating background organ (median [interquartile range]) 0.8 [0.7-0.9] vs. 2.6 [2.3-2.7]; P < 0.001). In addition, the sensitivity of [¹⁸F]AIF-FAPI-74 PET/CT in detecting metastatic lymph nodes was higher than that of [¹⁸F]FDG PET/CT (50.0% vs. 0.0%; P = 0.026).</p><p><strong>Conclusion: </strong>This study demonstrated that [¹⁸F]AIF-FAPI-74 PET/CT could improve the clinical staging of potentially resectable PDAC.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"1068-1077"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemokine Receptor 4-Targeted PET/CT with [⁶⁸Ga]pentixather in Newly Diagnosed Multiple Myeloma: a Comparative Study with [⁶⁸Ga]pentixafor PET/CT.","authors":"Qiao Yang, Fujing Zhang, Zhixin Hao, Junling Zhuang, Li Huo","doi":"10.1007/s11307-024-01953-7","DOIUrl":"10.1007/s11307-024-01953-7","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to compare the detection rate of [⁶⁸Ga]pentixather PET/CT and [⁶⁸Ga]pentixafor PET/CT in newly diagnosed multiple myeloma (NDMM) patients, and to explore the value of [⁶⁸Ga]pentixather PET/CT for tumor load assessment.</p><p><strong>Methods: </strong>Nineteen NDMM Patients were prospectively recruited and underwent both [⁶⁸Ga]pentixather PET/CT and [⁶⁸Ga]pentixafor PET/CT. A positive PET scan was defined as the presence of PET-positive focal bone lesions, paraskeletal disease, extramedullary plasmacytoma, or diffuse bone marrow uptake. Lesion numbers, SUVmax and PET-related tumor burden values were compared. The correlations between PET-related tumor burden and clinical risk stratification were analyzed.</p><p><strong>Results: </strong>[⁶⁸Ga]pentixather PET/CT showed a tendency of higher positive rate compared with [⁶⁸Ga]pentixafor PET/CT [94.7% (18/19) vs. 78.9% (15/19), p > 0.05]. Among 14 patients with 151 matched focal bone lesions, [⁶⁸Ga]pentixather PET detected more or equal number of lesions in 13 patients, and demonstrated higher uptake value than ⁶⁸ Ga-pentixafor PET [SUVmax, 16.8 (9.0, 23.8) vs. 13.4 (6.5, 20.4), p < 0.001]. For PET related-tumor burden, positive correlations of total bone marrow uptake (TBmU) (r = 0.9540, p < 0.0001) and SUVmean of total bone marrow (r = 0.9632, p < 0.0001) in two PET scans were observed. Higher TBmU [7864.9 (5549.2, 11,616.2) vs. 5383.4(4102.7, 11,041.8), p < 0.001], SUVmean of total bone marrow [1.4 (1.1, 2.2) vs. 1.1 (0.7, 2.1), p < 0.001] were demonstrated on [⁶⁸Ga]pentixather PET than [⁶⁸Ga]pentixafor PET. And the level of TBmU in [⁶⁸Ga]pentixather PET and [⁶⁸Ga]pentixafor PET were both elevated in Durie-Salmon Staging (DSS) III than DSS I (p < 0.01).</p><p><strong>Conclusions: </strong>[⁶⁸Ga]pentixather PET/CT performed a non-inferior capability for tumor detection compared to [⁶⁸Ga]pentixafor PET/CT in NDMM patients. [⁶⁸Ga]pentixather PET/CT can assess tumor load in MM patients and depict a significantly higher PET-related total tumor burden than [⁶⁸Ga]pentixafor PET/CT.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"986-994"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using GeoMx DSP Spatial Proteomics to Investigate Immune Infiltration of NOD Mouse Islet and Exocrine Compartments.","authors":"Hasim Tekin, Claes Lindhardt, Julie Christine Antvorskov, Nicolai Schou Bager, Signe Regner Michaelsen, Aušrinė Areškevičiūtė, Jonas Pordel Vind, Bjarne Winther Kristensen, Knud Josefsen","doi":"10.1007/s11307-024-01961-7","DOIUrl":"10.1007/s11307-024-01961-7","url":null,"abstract":"<p><strong>Purpose: </strong>Type 1 Diabetes (T1D) pathogenesis involves immune cells infiltrating pancreatic Islets of Langerhans, leading to T cell activation, beta cell destruction, and impaired insulin production. However, infiltration has a heterogenic nature that isn't described in detail, as not all islets are infiltrated. The aim of this study was to investigate if the observed heterogeneity is coupled to differences in immune and/or dysfunctional status of islets or exocrine cells, and if specific markers could elucidate mechanistic details of T1D pathogenesis.</p><p><strong>Procedures: </strong>The GeoMx platform was used to spatially quantify protein levels in pancreatic islets and exocrine tissue in Non-Obese Diabetic (NOD) mice. The protein panel included 17 immune activity markers and nine dysfunction markers. Immunohistochemical (IHC) staining and digital image analysis was used to analyze select marker proteins.</p><p><strong>Results: </strong>Use of the GeoMx platform to investigate T1D was shown to be possible, as Granzyme B protein levels were found to be lower in distal islet areas when compared to proximal areas. Smooth Muscle Actin protein levels were higher in exocrine areas proximal to immune-infiltrated islets, when compared to distally located exocrine areas. Findings from GeoMx were however not observed in IHC-stained sections.</p><p><strong>Conclusions: </strong>This study demonstrates that investigating T1D is possible with spatial proteomics, as the assays revealed presence of heterogenic islet areas in NOD mice, which may play a role in T1D progression and escape from immune recognition. This study highlights the potential of spatial technologies for elucidating T1D pathogenesis and future treatment strategies.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"943-954"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimisation of Animal Handing and Timing of 2-deoxy-2-[¹⁸F]fluoro-D-glucose PET Tumour Imaging in Mice.","authors":"Richard L Hesketh, David Y Lewis, Kevin M Brindle","doi":"10.1007/s11307-024-01956-4","DOIUrl":"10.1007/s11307-024-01956-4","url":null,"abstract":"<p><strong>Purpose: </strong>In humans, 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) tumour-to-background contrast continues to increase long after a typical uptake period of 45 - 60 min. Similar studies have not been performed in mice and the static imaging time point for most studies is arbitrarily set at 30 - 60 min post-injection of [¹⁸F]FDG. Ideally, static PET imaging should be performed after the initial period of rapid uptake but this period has not been defined in mice, with previous dynamic studies in mice being limited to 60 min. This study aimed to define the kinetics of [¹⁸F]FDG biodistribution over periods of 3 - 4 h in different murine tumour models, both subcutaneous and autochthonous, and to further refine fasting and warming protocols used prior to imaging.</p><p><strong>Procedures: </strong>Dynamic [¹⁸F]FDG PET-CT scans lasting 3 or 4 h were performed with C57BL/6 J and Balb/c nude mice bearing subcutaneous EL4 murine T-cell lymphoma and Colo205 human colorectal tumours, respectively, and with transgenic Eμ-Myc lymphoma mice. Prior to [¹⁸F]FDG injection, four combinations of different animal handling conditions were used: warming for 1 h at 31 °C; maintenance at room temperature (20 - 24 °C), fasting for 6 - 10 h and a fed state.</p><p><strong>Results: </strong>Tumour mean standardised uptake value (SUV_mean) peaked at 147 ± 48 min post injection in subcutaneous tumours and 74 ± 31 min in autochthonous Eμ-Myc lymphomas. The tumour-to-blood ratio (TBR) peaked at 171 ± 57 and 83 ± 33 min in subcutaneous and autochthonous Eμ-Myc tumours, respectively. Fasting increased tumour [¹⁸F]FDG uptake and suppressed myocardial uptake in EL4 tumour-bearing mice. There was a good correlation between tumour SUV_mean and K_i calculated using an input function (IDIF) derived from the inferior vena cava.</p><p><strong>Conclusions: </strong>Delayed static [¹⁸F]FDG-PET imaging (> 60 min) in both autochthonous and subcutaneous tumours in improved tumour-to-background contrast and increased reproducibility.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"965-976"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Imaging of Regional Cerebral Protein Synthesis in Clinical Alzheimer's Disease by [¹¹C]Leucine PET.","authors":"Karl Herholz, Adam McMahon, Jennifer C Thompson, Matthew Jones, Herve Boutin, Jamil Gregory, Christine A Parker, Rainer Hinz","doi":"10.1007/s11307-024-01965-3","DOIUrl":"10.1007/s11307-024-01965-3","url":null,"abstract":"<p><strong>Purpose: </strong>Protein synthesis is essential to maintain integrity and function of the human brain, and protein synthesis is associated specifically with the formation of long-term memory. Experimental and clinical observations indicate that this process is disturbed in Alzheimer's dementia and other neurodegenerative diseases. In-vivo investigation with positron emission tomography (PET) using [¹¹C]leucine provides a unique possibility to measure regional cerebral protein synthesis (rCPS) rates in human brain and to determine whether it is altered in Alzheimer's disease (AD), and thus may provide a target for future therapeutic interventions.</p><p><strong>Procedures: </strong>In this first human study, we measured rCPS by [¹¹C]leucine PET in four patients with AD (age 57-73 years) and compared the results with six healthy controls (three of whom were age matched and the other three were young controls). Quantification of rCPS also required measurement of amino acid (AA) levels and of free and protein-bound [¹¹C]leucine in plasma during the 90 min PET scans conducted following at least six hours of fasting.</p><p><strong>Results: </strong>Rates of rCPS measured in absolute units of nmol/g/min ranged between 1.81 and 2.53 in AD patients, 2.10 and 2.54 in matched controls, and 2.21 to 2.35 in the young controls. Mean and median values did not show significant differences between the groups. Rates of rCPS also depended upon whether corrections for plasma AA levels were included in the calculations. When considering regional values relative to the corpus callosum as a reference region, there was a tendency towards impairment of rCPS in patients, which was most prominent in the parietal cortex, but did not reach significance. Similar findings were observed with normalisation of rCPS to global cortical mean.</p><p><strong>Conclusions: </strong>In summary, this first human study assessing regional protein synthesis with [¹¹C]leucine in AD has demonstrated where the sources of variance in measurements of cerebral protein synthesis may arise, along with the potential magnitude of this variance. This study also indicates that there is a tendency towards impairment of rCPS in patients with Alzheimer's disease, which requires further investigation including possible partial volume effects due to atrophy.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"977-985"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation Between Responders and Non-Responders to Antibiotic Treatment in Mice Using ¹⁸F-Fluorodeoxysorbitol/PET.","authors":"Junling Li, Huaiyu Zheng, Jenna Olson, Jonathan M Warawa, Chin K Ng","doi":"10.1007/s11307-024-01957-3","DOIUrl":"10.1007/s11307-024-01957-3","url":null,"abstract":"<p><strong>Purpose: </strong>Bacterial infection causes significant mortality and morbidity worldwide despite the availability of antibiotics. Differentiation between responders and non-responders early on during antibiotic treatment will be informative to patients and healthcare providers. Our objective was to investigate whether PET imaging with ¹⁸F-Fluorodeoxysorbitol (¹⁸F-FDS) or ¹⁸F-FDG can be used to differentiate responders from non-responders to antibiotic treatment.</p><p><strong>Procedures: </strong>NTUH-K2044 was used for infection in Albino C57 female mice. Each mouse was inoculated intratracheally with NTUH-K2044 to induce lung infection (n = 8). For treatment studies, two bacterial doses for animal inoculation and two treatment starting times were compared to optimize treatment profiles. ¹⁸F-FDS or ⁸F-FDG /PET imaging was performed to monitor treatment progression.</p><p><strong>Results: </strong>Our results demonstrated that the treatment profiles for mice infected with 25 CFU hvKp and antibiotic treatment starting at 24 p.i. were not ideal due to no evidence of lung infection and lack of treatment efficacy. The optimal scheme is to use 250 CUF for infection and start antibiotic treatment at 24 h p.i. to monitor antimicrobial efficacy. 75% of the mice were classified as responders to antibiotic treatment. 25% of the mice were classified as non-responders. ¹⁸F-FDG was used to compare with ¹⁸F-FDS, but all mice showed increased lung uptake of ¹⁸F-FDG during 3-day treatments.</p><p><strong>Conclusions: </strong>¹⁸F-FDS is a promising PET tracer to image bacterial infection. It can be used to monitor response to treatment, and differentiate responders from non-responders to antibiotic treatment, but ¹⁸F-FDG cannot, probably due to the presence of high degree of inflammation before and after treatment.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"934-942"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Neoadjuvant Therapy on Tumour Target Expression of Oesophageal Cancer Tissue for NIR Fluorescence Imaging.","authors":"Hidde A Galema, Lisanne K A Neijenhuis, Lorraine J Lauwerends, N Geeske Dekker-Ensink, Cornelis Verhoef, Alexander L Vahrmeijer, Shadhvi S Bhairosingh, Peter J K Kuppen, Stephan Rogalla, Jacobus Burggraaf, Sjoerd M Lagarde, Bas P L Wijnhoven, Merlijn Hutteman, Michail Doukas, Stijn Keereweer, Denise E Hilling","doi":"10.1007/s11307-024-01962-6","DOIUrl":"10.1007/s11307-024-01962-6","url":null,"abstract":"<p><strong>Purpose: </strong>Oesophaegal cancer patients with a clinical complete response (CR) after neoadjuvant chemoradiotherapy (nCRT) are candidates for an active surveillance strategy. Regrowth rates of 40% after initial clinical CR indicate that identification of a true complete response to nCRT remains challenging. Near-infrared tumour-specific fluorescence endoscopic imaging might help to discriminate patients with a true complete response from patients with residual disease. This study aims to find potential markers to enable molecular imaging in oesophageal cancer and to assess the effect of nCRT on marker expression.</p><p><strong>Procedures: </strong>Oesophageal cancer tissue slides of diagnostic biopsies (n = 41) (pre-treatment) and paired surgical specimens (n = 31) (post-treatment) were collected. Tissue slides of patients with adenocarcinoma (n = 29) and squamous cell carcinoma (n = 12)) were included. Immunohistochemistry was performed to assess expression of the tumour markers CEA, EpCAM, VEGF-α, EGFR, and c-MET in the tumour and compared to the expression of these markers in surrounding healthy tissue. A total immunostaining score (TIS, range 0-12), which combines the percentage and intensity of stained cells, was calculated. The TIS of pre-treated biopsies were compared with the TIS of the post-treatment surgical specimens to assess the effect of neoadjuvant therapy on the marker expression.</p><p><strong>Results: </strong>The median TIS of EpCAM in adenocarcinomas was 10, vs. 0 in healthy mucosa (p < 0.001). The median TIS of EGFR in squamous cell carcinoma was 12, vs. 4 in healthy mucosa (p < 0.001). Neoadjuvant therapy did not affect the expression of the markers.</p><p><strong>Conclusion: </strong>EpCAM and EGFR appear to be the most suitable targets for tumour-specific NIR fluorescence imaging of oesophageal adenocarcinoma and squamous cell carcinoma, respectively. Unaffected expression of all suitable markers by neoadjuvant therapy implies that the diagnostic biopsy can be used to select a patient-specific target for response evaluation by molecular imaging.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"955-964"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymidine Phosphorylase Imaging Probe for Differential Diagnosis of Metabolic dysfunction-associated Steatohepatitis.","authors":"Kei Higashikawa, Riho Uehara, Sawako Horiguchi, Yuki Shibata, Naoto Okubo, Yuki Mizuno, Hironobu Yasui, Shunsuke Ohnishi, Hiroshi Takeda, Yuji Kuge","doi":"10.1007/s11307-024-01964-4","DOIUrl":"10.1007/s11307-024-01964-4","url":null,"abstract":"<p><strong>Purpose: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises simple steatosis (SS), which has a low risk of mortality, and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to liver cirrhosis and hepatocellular carcinoma. Because differentiation between MASH and SS is the most important issue in the diagnosis of MASLD, the establishment of noninvasive diagnostic methods is urgently needed. In this study, we evaluated the potential of [¹²³I]IIMU, a thymidine phosphorylase (TYMP) targeted SPECT imaging probe, for differential diagnosis of MASLD in a preclinical animal model.</p><p><strong>Procedures: </strong>SS and MASH mice were prepared by feeding db/db mice with a standard diet and a methionine/choline-deficient diet, respectively. Control mice were prepared by feeding m/m mice with a standard diet. TYMP expression in the liver was evaluated by RT-PCR, western blotting, and immunohistochemistry. The biodistribution of [¹²⁵I]IIMU in the three model mice was evaluated at 30 min post-injection. SPECT/CT imaging studies of the three model mice were performed 30 min after injection of [¹²³I]IIMU.</p><p><strong>Results: </strong>Hepatic TYMP expression level was the highest in the SS mice and the lowest in the MASH mice at both mRNA and protein levels. The immunohistochemistry experiment showed a patchy distribution of TYMP only in the liver of MASH mice. In the biodistribution study, the hepatic accumulation of [¹²⁵I]IIMU was the highest in the SS mice and the lowest in the MASH mice. The SPECT/CT imaging study showed similar results to the biodistribution experiment.</p><p><strong>Conclusion: </strong>Hepatic TYMP expression level may serve as a promising imaging biomarker for differential diagnosis of SS and MASH. SPECT imaging using [¹²³I]IIMU potentially provides a novel noninvasive diagnostic method to differentiate MASH and SS.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"1036-1045"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}