Molecular Imaging and Biology最新文献

{"title":"Visions by WIMIN: Imposter Phenomenon.","authors":"Eman Akam-Baxter, Christine M O'Brien, Sanhita Sinharay, Veronica Clavijo-Jordan, Susana Bulnes Rodriguez, Jenny Nneka Ijoma, Anmol Kustagi, Mahnue Sahn, Fatoumata Diop, Kyeara Mack, Natasha Malonza, Natalia Herrero Alvarez","doi":"10.1007/s11307-024-01971-5","DOIUrl":"10.1007/s11307-024-01971-5","url":null,"abstract":"<p><p>The imposter phenomenon (IP) is a destructive set of beliefs, traits, and experiences in which high-achieving individuals fail to internalize their accomplishments and falsely perceive themselves as frauds. IP is a function of underrepresentation and contributes to and perpetuates a cycle of low self-worth, perfectionism, and anxiety, all of which negatively affect job performance and reinforce the IP cycle. Mitigating the deleterious effects of IP requires first naming this phenomenon and recognizing the patterns of IP. In this article, we summarize pertinent social science literature on this topic and share experiences of IP as told by the authors and anonymous contributors. We highlight the potential destructive effects of IP, as well as strategies that mentors and trainees can utilize to counter this phenomenon.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"17-22"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951859","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":"First-in-human Evaluation of Safety and Dosimetry of [⁶⁴Cu]FBP8: A fibrin-binding PET Probe.","authors":"David Izquierdo-Garcia, Pauline Désogère, Anne L Philip, David E Sosnovik, Ciprian Catana, Peter Caravan","doi":"10.1007/s11307-024-01973-3","DOIUrl":"10.1007/s11307-024-01973-3","url":null,"abstract":"<p><strong>Purpose: </strong>This study presents for the first time in humans the biodistribution, clearance and dosimetry estimates of [⁶⁴Cu]Fibrin Binding Probe #8 ([⁶⁴Cu]FBP8) in healthy subjects. [⁶⁴Cu]FBP8-PET previously demonstrated its potential in two recent applications: thrombus imaging and pulmonary fibrosis.</p><p><strong>Procedures: </strong>This prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [⁶⁴Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 h, 4 h and 24 h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software.</p><p><strong>Results: </strong>Subjects were injected with 400 MBq of [⁶⁴Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [⁶⁴Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG, 0.020mSv/MBq).</p><p><strong>Conclusions: </strong>This study demonstrates the following properties of the [⁶⁴Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 min in a single session. These properties provide the basis for [⁶⁴Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"99-108"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780530","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":"Deep Radiogenomics Sequencing for Breast Tumor Gene-Phenotype Decoding Using Dynamic Contrast Magnetic Resonance Imaging.","authors":"Isaac Shiri, Yazdan Salimi, Pooya Mohammadi Kazaj, Sara Bagherieh, Mehdi Amini, Abdollah Saberi Manesh, Habib Zaidi","doi":"10.1007/s11307-025-01981-x","DOIUrl":"10.1007/s11307-025-01981-x","url":null,"abstract":"<p><strong>Purpose: </strong>We aim to perform radiogenomic profiling of breast cancer tumors using dynamic contrast magnetic resonance imaging (MRI) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) genes.</p><p><strong>Methods: </strong>The dataset used in the current study consists of imaging data of 922 biopsy-confirmed invasive breast cancer patients with ER, PR, and HER2 gene mutation status. Breast MR images, including a T1-weighted pre-contrast sequence and three post-contrast sequences, were enrolled for analysis. All images were corrected using N4 bias correction algorithms. Based on all images and tumor masks, a bounding box of 128 × 128 × 68 was chosen to include all tumor regions. All networks were implemented in 3D fashion with input sizes of 128 × 128 × 68, and four images were input to each network for multi-channel analysis. Data were randomly split into train/validation (80%) and test set (20%) with stratification in class (patient-wise), and all metrics were reported in 20% of the untouched test dataset.</p><p><strong>Results: </strong>For ER prediction, SEResNet50 achieved an AUC mean of 0.695 (CI95%: 0.610-0.775), a sensitivity of 0.564, and a specificity of 0.787. For PR prediction, ResNet34 achieved an AUC mean of 0.658 (95% CI: 0.573-0.741), a sensitivity of 0.593, and a specificity of 0.734. For HER2 prediction, SEResNext101 achieved an AUC mean of 0.698 (95% CI: 0.560-0.822), a sensitivity of 0.750, and a specificity of 0.625.</p><p><strong>Conclusion: </strong>The current study demonstrated the feasibility of imaging gene-phenotype decoding in breast tumors using MR images and deep learning algorithms with moderate performance.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"32-43"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008565","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":"PET Imaging of a Transgenic Tau Rat Model SHR24 with [¹⁸F]AV1451.","authors":"Nisha K Ramakrishnan, Annie Ziyi Zhao, Stephen Thompson, Selena Milicevic Sephton, David J Williamson, Tomáš Smolek, Norbert Žilka, Franklin I Aigbirhio","doi":"10.1007/s11307-024-01972-4","DOIUrl":"https://doi.org/10.1007/s11307-024-01972-4","url":null,"abstract":"<p><strong>Purpose: </strong>Positron Emission Tomography (PET) scans with radioligands targeting tau neurofibrillary tangles (NFT) have accelerated our understanding of the role of misfolded tau in neurodegeneration. While intended for human research, applying these radioligands to small animals establishes a vital translational link. Transgenic animal models of dementia, such as the tau rat SHR24, play a crucial role in enhancing our understanding of these disorders. This study aims to evaluate the utility of SHR24 rat model for PET studies.</p><p><strong>Procedures: </strong>Dynamic PET scans were conducted in male SHR24 rats and their wild-type SHR (SHRwt) littermates using [¹⁸F]AV1451. Rapid blood sampling and metabolite analysis were performed to acquire input curves. Time activity curves were obtained from various brain regions over 60 min. Blood-based, 2-Tissue Compartment Model (2-TCM) and Logan graphical analysis were used to obtain kinetic modelling parameters. The ability of reference tissue models to predict the binding potential (BP_ND) were assessed. Autoradiography studies were performed to corroborate the scan data.</p><p><strong>Results: </strong>Total distribution volume (V_T) was the best predicted parameter which revealed significantly higher uptake of [¹⁸F]AV1451 in the cortex (5.8 ± 1.1 vs 4.6 ± 0.7, P < 0.05) of SHR24 rats compared to SHRwt rats. Binding potential obtained from 2-TCM was variable, however BP_ND from reference tissue models detected significantly higher binding in cortex (0.28 ± 0.07 vs 0.20 ± 0.04, P < 0.01 by SRTM) and brainstem (0.14 ± 0.04 vs 0.08 ± 0.02, P < 0.01, by SRTM).</p><p><strong>Conclusions: </strong>With the ability to detect binding of established radioligand [¹⁸F]AV1451 in these rats, we have demonstrated the utility of this model for assessing aggregated tau neurobiology by PET, with reference tissue models providing potential for longitudinal studies.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008566","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":"Autoradiography of Intracerebral Tumours in the Chick Embryo Model: A Feasibility Study Using Different PET Tracers.","authors":"Sandra Krause, Alexandru Florea, Chang-Hoon Choi, Wieland A Worthoff, Alexander Heinzel, Saskia Fischer, Nicole Burda, Bernd Neumaier, N Jon Shah, Philipp Lohmann, Felix M Mottaghy, Karl-Josef Langen, Carina Stegmayr","doi":"10.1007/s11307-025-01983-9","DOIUrl":"https://doi.org/10.1007/s11307-025-01983-9","url":null,"abstract":"<p><strong>Purpose: </strong>In addition to rodent models, the chick embryo model has gained attention for radiotracer evaluation. Previous studies have investigated tumours on the chorioallantoic membrane (CAM), but its value for radiotracer imaging of intracerebral tumours has yet to be demonstrated.</p><p><strong>Procedures: </strong>Human U87 glioblastoma cells and U87-IDH1 mutant glioma cells were implanted into the brains of chick embryos at developmental day 5. After 12-14 days of tumour growth, blood-brain-barrier integrity was evaluated in vivo using MRI contrast enhancement or ex vivo with Evans blue dye. The tracers O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) (n = 5), 3,4-dihydroxy-6-[¹⁸F]-fluoro-L-phenylalanine ([¹⁸F]FDOPA) (n = 3), or [⁶⁸Ga] labelled quinoline-based small molecule fibroblast activation protein inhibitor ([⁶⁸Ga]FAPI-46) (n = 4) were injected intravenously if solid tumours were detected with MRI. For time-activity curves for [¹⁸F]FET, additional micro PET (µPET) was performed. The chick embryos were sacrificed 60 min post-injection, and cryosections of the tumour-bearing brains were produced and evaluated with autoradiography and immunohistochemistry.</p><p><strong>Results: </strong>Intracerebral tumours were produced with a 100% success rate in viable chick embryos at the experimental endpoint. However, 52% of chick embryos (n = 85) did not survive the procedure to embryonic development day 20. For the evaluated radiotracers, the tumour-to-brain ratios (TBR) derived from ex vivo autoradiography, as well as the tracer kinetics derived from µPET for intracerebral chick embryo tumours, were comparable to those previously reported in rodents and patients: the TBRmean for [¹⁸F]FET was 1.69 ± 0.54 (n = 5), and 3.8 for one hypermetabolic tumour and < 2.0 for two isometabolic tumors using [¹⁸F]FDOPA, with a TBRmean of 1.92 ± 1,11 (n = 3). The TBRmean of [⁶⁸Ga]FAPI-46 for intracerebral chick embryo tumours was 19.13 ± 0.64 (n = 4). An intact blood-tumour barrier was observed in one U87-MG tumour (n = 5).</p><p><strong>Conclusions: </strong>Radiotracer imaging of intracerebral tumours in the chick embryo offers a fast model for the evaluation of radiotracer uptake, accumulation, and kinetics. Our results indicate a high comparability between intracerebral tumour imaging in chick embryos and xenograft rodent models or brain tumour patients.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008564","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":"2024 World Molecular Imaging Congress Program.","authors":"","doi":"10.1007/s11307-024-01977-z","DOIUrl":"10.1007/s11307-024-01977-z","url":null,"abstract":"","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"761-1256"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370880","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":"Improved Quantification of MicroPET/CT Imaging Using CT-derived Scaling Factors.","authors":"Ayon Nandi, Masayoshi Nakano, James Robert Brašić, Zabecca S Brinson, Kelly Kitzmiller, Anil Mathur, Mona Mohamed, Joshua Roberts, Dean F Wong, Hiroto Kuwabara","doi":"10.1007/s11307-024-01947-5","DOIUrl":"10.1007/s11307-024-01947-5","url":null,"abstract":"<p><strong>Purpose: </strong>Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dimensions and consequently estimates of nondisplaceable binding potential (BP_ND) in rodent PET studies.</p><p><strong>Procedures: </strong>PET and CT scans were acquired on 5 female and 5 male CD-1 mice with 3-[¹⁸F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([¹⁸F]FPEB), a radiotracer for the metabotropic glutamate receptor subtype 5 (mGluR5). In the proposed PET/CT (PTCT) approach, the tracer-specific standard volume was dimension-customized to each animal using the scaling factors from CT-to-standard CT coregistration to simplify PET-to-standard PET coregistration (i.e., 3 CT- and 6 PET-derived parameters). For comparison, conventional PET-based coregistration was performed with 9 (PT9) or 12 (PT12) parameters. PET frames were transferred to the standard space by the three approaches (PTCT, PT9, and PT12) to obtain regional time-activity curves (TACs) and BP_ND in 14 standard volumes of interest (VOIs). Lastly, CT images of the animals were transferred to the standard space by CT-based parameters from PTCT and with the scaling factors replaced with those from PET-based PT9 to evaluate agreement of the skull to the standard CT.</p><p><strong>Results: </strong>The PET-based approaches showed various degrees of underestimations of scaling factors in the posterior-anterior-direction compared to PTCT, which resulted in negatively proportional overestimation of radioactivity in the cerebellum (reference region) up to 20%, and proportional, more prominent underestimation of BP_ND in target regions down to -50%. The skulls of individual animals agreed with the standard skull for scaling factors from PTCT but not for the scaling factors from PT9, which suggested inaccuracy of the latter.</p><p><strong>Conclusions: </strong>The results indicated that conventional PET-based coregistration approaches could yield biased estimates of BP_ND in proportion to errors of brain dimensions when applied to tracers for which the cerebellum serves as reference region. The proposed PTCT provides evidence of a quantitative improvement over PET-based approaches for brain studies using micro-PET/CT scanners.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"1016-1026"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308078","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":"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":"Evaluations of a Cutaneous Wound Healing Model Using Oxygen Enhanced - Dynamic Contrast Enhanced Photoacoustic Imaging (OE-DCE PAI).","authors":"Euitaek Yang, Alia Khaled, Xiaofei Liang, Jorge de la Cerda, F William Schuler, Shreya Goel, Mark D Pagel","doi":"10.1007/s11307-024-01966-2","DOIUrl":"10.1007/s11307-024-01966-2","url":null,"abstract":"<p><strong>Purpose: </strong>Preclinical models of cutaneous wound healing can be useful for improving clinical wound care. Oxygen Enhanced Photoacoustic imaging (OE PAI) can measure oxygenation, and Dynamic Contrast Enhanced (DCE) PAI can measure vascular perfusion. We investigated how a combined OE-DCE PAI protocol can measure vascular oxygenation and perfusion to a cutaneous healing model.</p><p><strong>Procedures: </strong>We developed a cutaneous \"punch\" wound model and photographed the wounds to track healing for 9 days. We performed OE-DCE PAI on Day 0, 3, 6, and 9. OE PAI was performed with 21% O₂ and 100% O₂ breathing gases to measure oxyhemoglobin (HbO₂), deoxyhemoglobin (Hb), total hemoglobin (HbT), and oxygen saturation (%sO₂), along with changes in these parameters caused by a change in breathing gas (ΔHb, ΔHbO₂, ΔHbT, ΔsO₂). To perform DCE PAI, indocyanine green (ICG) was administered intravenously while monitoring the PAI signal for 10 min as the agent washed through the wound area, which was used to evaluate the wash-out rate.</p><p><strong>Results: </strong>The average wound size was significantly smaller only by Day 6. For comparison, OE PAI measured a significant increase in HbO₂, Hb, HbT, and %sO₂ immediately after creating the wound, which significantly decreased by Day 3 and continued to decrease towards values for normal tissue by Day 9. The vascular wash-out rate significantly increased by Day 3, and continued to increase during the healing process. Notably, the wash-out rate can be assessed at a single PAI absorbance wavelength and by simply comparing signal amplitudes without advanced analysis, which may facilitate clinical translation.</p><p><strong>Conclusions: </strong>OE-DCE PAI can monitor significant changes in vascular perfusion and oxygenation prior to significant changes in cutaneous wound size. These results establish OE-DCE PAI as a tool for future pre-clinical wound healing studies and eventual clinical translation.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"995-1004"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624186","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":"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}