Molecular Imaging and Biology最新文献

{"title":"Correction: Preclinical Development of Near-Infrared-Labeled CD38-Targeted Daratumumab for Optical Imaging of CD38 in Multiple Myeloma.","authors":"Nicholas Cho, Sooah Ko, Monica Shokeen","doi":"10.1007/s11307-025-01984-8","DOIUrl":"https://doi.org/10.1007/s11307-025-01984-8","url":null,"abstract":"","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557287","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":"Correction: Evaluation of [¹⁸F]AlF NOTA-5G, an Aluminum [¹⁸F]fluoride Labeled Peptide Targeting the Cell Surface Receptor Integrin Alpha(v)beta(6) for PET Imaging.","authors":"Sven H Hausner, Ryan A Davis, Tanushree Ganguly, Rebecca Harris, Julie L Sutcliffe","doi":"10.1007/s11307-025-01995-5","DOIUrl":"https://doi.org/10.1007/s11307-025-01995-5","url":null,"abstract":"","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557285","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":"Spatial FAP Expression as Detected by ⁶⁸ Ga-FAPI-46 Identifies Myofibroblasts Beyond the Infarct Scar After Reperfusion.","authors":"Annika Hess, Alexandra Renko, Andreas Schäfer, Mira Jung, Daniela Fraccarollo, Jan D Schmitto, Johanna Diekmann, Thomas Thum, Frank M Bengel, Johann Bauersachs, James T Thackeray, Jochen Tillmanns","doi":"10.1007/s11307-025-01994-6","DOIUrl":"https://doi.org/10.1007/s11307-025-01994-6","url":null,"abstract":"<p><strong>Purpose: </strong>Myocardial infarction (MI) triggers complex cellular responses essential for tissue repair and remodeling, including myofibroblast activation. Fibroblast activation protein alpha (FAP) identifies activated myofibroblasts post-MI, however its spatial distribution relative to the scar and area at risk (AAR) is unclear. Non-invasive FAP-imaging with PET radiotracer ⁶⁸ Ga-FAPI-46 shows uptake beyond the infarct scar. We therefore aimed to characterize FAP expression in the AAR using a myocardial ischemia-reperfusion (MI/R) model in mice.</p><p><strong>Procedures: </strong>We induced MI/R in male C57BL/6N mice. The AAR was identified by in vivo lectin staining, and expression of FAP, CD68, and hypoxic tissues were measured using immunohistochemistry. Spatial FAP was further interrogated by ⁶⁸ Ga-FAPI-46 in mice by autoradiography and humans by PET. Additionally, human cardiac tissues from acute MI patients were examined for fibroblasts and inflammatory cells by expression of FAP, CD13, and α-smooth muscle actin.</p><p><strong>Results: </strong>FAP expression peaked three days post-MI/R predominantly within the AAR (p < 0.05 vs. d0). Consistent between murine models and human tissues, FAP⁺ myofibroblasts accumulated within the infarct scar and borderzone, occasionally extending into non-ischemic myocardium. CD68⁺ macrophages peaked similarly at three days post-MI/R (p < 0.05 vs. d0). FAP expression weakly correlated with CD68 but not with extent of ischemic or hypoxic territory post-MI/R. FAP imaging in mice and humans revealed aligned non-uniform ⁶⁸ Ga-FAPI-46 uptake extending from the infarct scar into surviving myocardium after MI.</p><p><strong>Conclusions: </strong>Our findings demonstrate a distinct FAP expression pattern post-MI/R. The alignment of ex vivo ⁶⁸ Ga-FAPI-46 signal with myofibroblasts in the AAR supports its identification of a unique substrate in myocardial injury complementing other non-invasive imaging measurements of perfusion, viability and fibrosis.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542445","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":"Quantifying Molecular Changes in the Preeclamptic Rat Placenta with Targeted Contrast-Enhanced Ultrasound Imaging.","authors":"Lili Shi, Allan K N Alencar, Kenneth F Swan, Dylan J Lawrence, Gabriella Pridjian, Carolyn L Bayer","doi":"10.1007/s11307-025-01988-4","DOIUrl":"https://doi.org/10.1007/s11307-025-01988-4","url":null,"abstract":"<p><strong>Purpose: </strong>Abnormal placental remodeling is linked to various pregnancy-related diseases, including preeclampsia (PE). This study applies a bicompartmental (BCM) model to quantify molecular expression changes in the placenta, indicative of abnormal placental remodeling, and evaluates the effectiveness of targeted contrast-enhanced ultrasound (T-CEUS) in detecting the abnormal placental vasculature. The BCM model provides high temporal resolution and differentiation of anatomical artery structures within the placenta by analyzing the distribution of contrast agents.</p><p><strong>Methods: </strong>A targeted contrast agent (TCA) composed of gas-filled microbubbles (MB), with a surface-conjugated peptide to target α_νβ₃ integrin, a biomarker for angiogenesis, was used for quantifying placental vascular development. CEUS images were acquired from timed pregnant Sprague Dawley rats with experimentally-induced reduced uterine perfusion pressure (RUPP) placental insufficiency. On gestational day (GD) 18 of a 21-day gestation, CEUS images were acquired from both Normal pregnant (NP; n = 6) and RUPP (n = 6) dams after injection of the TCA. The BCM model was used to estimate the binding dynamics of the TCA, providing a parametric map of the binding constant ( <math><msub><mi>K</mi> <mi>b</mi></msub> </math> ) of the placenta.</p><p><strong>Results: </strong>The RUPP group showed a significant reduction in the value of <math><msub><mi>K</mi> <mi>b</mi></msub> </math> compared to the NP group (p < 0.05). A histogram of the placental <math><msub><mi>K</mi> <mi>b</mi></msub> </math> was compared to alternative analyses (differential target enhancement, dTE and late enhancement, LE) to demonstrate that it can differentiate between anatomical artery structures with a higher contrast-to-background ratio.</p><p><strong>Conclusions: </strong>The BCM method differentiates molecular changes associated with the abnormal placental development associated with PE. It also reveals more intricate internal anatomical structures of the placenta in comparison to dTE and LE, suggesting that the BCM could enhance early detection and monitoring of PE.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516189","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":"Evaluation of [¹⁸F]JNJ-CSF1R-1 as a Positron Emission Tomography Ligand Targeting Colony-Stimulating Factor 1 Receptor.","authors":"Mani Salarian, Shuanglong Liu, Hsiu-Ming Tsai, Shannon N Leslie, Thomas Hayes, Su-Tang Lo, Anna K Szardenings, Wei Zhang, Gang Chen, Christine Sandiego, Lisa Wells, Dileep G Nair, Hartmuth C Kolb, Chunfang A Xia","doi":"10.1007/s11307-025-01991-9","DOIUrl":"https://doi.org/10.1007/s11307-025-01991-9","url":null,"abstract":"<p><strong>Purpose: </strong>Colony-stimulating factor 1 receptor (CSF1R) signaling plays a pivotal role in neuroinflammation, driving microglia proliferation and activation. CSF1R is considered a hallmark of inflammation in many neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Our study aims to evaluate the potential value of 5-cyano-N-(4-(4-(2-([¹⁸F]fluoro)ethyl)piperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide ([¹⁸F]JNJ-CSF1R-1) as a positron emission tomography (PET) ligand targeting CSF1R in preclinical models of neuroinflammation.</p><p><strong>Procedures: </strong>A cell-based MSD assay was used to measure the IC₅₀ of 5-cyano-N-(4-(4-(2-(fluoro)ethyl)piperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide (JNJ-CSF1R-1). JNJ-CSF1R-1 was radiolabeled with fluorine-18. PET imaging was used to evaluate brain uptake, and target engagement of [¹⁸F]JNJ-CSF1R-1 in two neuroinflammation mouse models, including systemic lipopolysaccharide (LPS) and App^SAA knock in (KI). CSF1R protein levels in brain tissue were determined by western blot and ELISA assays. [¹⁸F]JNJ-CSF1R-1 brain uptake was also measured in a non-human primate (NHP) PET study.</p><p><strong>Results: </strong>JNJ-CSF1R-1 is a 12 nM (IC₅₀) inhibitor of CSF1R. ​[¹⁸F]JNJ-CSF1R-1 demonstrated significantly higher brain uptake in both LPS and AD mouse models as measured by the area under the time activity curves (AUC) compared to control animals. In the App^SAA KI model, CSF1R levels increased near amyloid plaques as detected by IHC. ​[¹⁸F]JNJ-CSF1R-1 PET imaging signal showed a good correlation with CSF1R expression levels measured by western blot and ELISA. In an NHP study, ​[¹⁸F]JNJ-CSF1R-1 readily entered the brain and demonstrated reversible kinetics.</p><p><strong>Conclusion: </strong>​[¹⁸F]JNJ-CSF1R-1 is a potent and promising CSF1R PET tracer with translational potential for measuring microglia-based neuroinflammatory processes and for tracking the impact of anti-inflammatory therapies.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502576","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":"Evaluation of [¹⁸F]AlF NOTA-5G, an Aluminum [¹⁸F]fluoride Labeled Peptide Targeting the Cell Surface Receptor Integrin Alpha(v)beta(6) for PET Imaging.","authors":"Sven H Hausner, Ryan A Davis, Tanushree Ganguly, Rebecca Harris, Julie L Sutcliffe","doi":"10.1007/s11307-025-01989-3","DOIUrl":"10.1007/s11307-025-01989-3","url":null,"abstract":"<p><strong>Purpose: </strong>Peptide-based probes targeting integrin α_vβ₆ have shown promise in clinical trials for cancer imaging based on the high over-expression of this epithelial-specific cell surface receptor in many cancerous tissues. Recently, the α_vβ₆-targeting gallium-68 labeled DOTA-5G peptide, [⁶⁸Ga]Ga DOTA-5G, demonstrated diagnostic value in patients with metastatic pancreatic cancer. To facilitate adoption at sites without access to gallium-68 and take advantage of the characteristics of fluorine-18 through convenient [¹⁸F]fluoride chelation chemistry, this study evaluated the fluorine-18 labeled analog, [¹⁸F]AlF NOTA-5G, in vitro and in vivo in a tumor mouse model, and compared it to [⁶⁸Ga]Ga DOTA-5G.</p><p><strong>Procedures: </strong>NOTA-5G was synthesized on solid phase and radiolabeled with aluminum [¹⁸F]fluoride to generate [¹⁸F]AlF NOTA-5G. Cell binding and internalization of [¹⁸F]AlF NOTA-5G were evaluated in paired DX3puroβ6 (α_vβ₆ +) and DX3puro (α_vβ₆ -), and pancreatic BxPC-3 (α_vβ₆ +) cells. Imaging (1-6 h) and biodistribution were performed in BxPC-3 tumor-bearing mice.</p><p><strong>Results: </strong>[¹⁸F]AlF NOTA-5G was obtained in > 93% radiochemical purity. Cell binding was α_vβ₆-targeted (1 h: 66% bound to DX3puroβ6, vs 2% to DX3puro), and ≥ 50% of bound activity was internalized; analogous to [⁶⁸Ga]Ga DOTA-5G, PET imaging showed clearly delineated tumors. Excretion remained primarily renal (1 to 4 h: 18.6 to 12.5% ID/g). Tumor uptake remained relatively steady (1 to 4 h: 2.3 ± 0.4 to 1.8 ± 0.6% ID/g - closely matching [⁶⁸Ga]Ga DOTA-5G with 2.6 ± 0.8 and 2.0 ± 0.6% ID/g at 1 and 2 h), resulting in tumor/pancreas, tumor/liver, and tumor/blood ratios of 18/1, 24/1, and 162/1, respectively (4 h); by comparison, for [⁶⁸Ga]Ga DOTA-5G the values were 21/1, 20/1, and 22/1 (2 h).</p><p><strong>Conclusions: </strong>[¹⁸F]AlF NOTA-5G demonstrated selective α_vβ₆-targeting and tumor uptake similar to [⁶⁸Ga]Ga DOTA-5G. The tumor-to-background ratio resulted high-contrast PET images, with an extended imaging window compared to [⁶⁸Ga]Ga DOTA-5G. The synthesis of [¹⁸F]AlF NOTA-5G is currently being optimized for clinical production.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468689","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":"Leveraging Radiomics and Hybrid Quantum-Classical Convolutional Networks for Non-Invasive Detection of Microsatellite Instability in Colorectal Cancer.","authors":"T Buvaneswari, M Ramkumar, Prabhu Venkatesan, R Sarath Kumar","doi":"10.1007/s11307-025-01990-w","DOIUrl":"https://doi.org/10.1007/s11307-025-01990-w","url":null,"abstract":"<p><strong>Purpose: </strong>The goal of this study is to create a novel framework for identifying MSI status in colorectal cancer using advanced radiomics and deep learning strategies, aiming to enhance clinical decision-making and improve patient outcomes in oncology.</p><p><strong>Procedures: </strong>The study utilizes histopathological slide images from the NCT-CRC-HE-100 K and PAIP 2020 databases. Key procedures include self-attentive adversarial stain normalization for data standardization, tumor delineation via a Slimmable Transformer, and radiomics feature extraction using a hybrid quantum-classical neural network.</p><p><strong>Results: </strong>The proposed system reaches 99% accuracy when identifying colorectal cancer MSI status. It shows the model is good at telling the difference between MSI and MSS tumors and can be used in real medical care for cancer.</p><p><strong>Conclusions: </strong>Our research shows that the new system improves colorectal cancer MSI status determination better than previous methods. Our optimized processing technology works better than other methods to divide and analyze tissue features making the system good for improving patient care decisions.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468694","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":"Test-retest Assessment of Biventricular Myocardial Oxidative Metabolism and Perfusion in Pulmonary Hypertension Patients Using ¹¹C-acetate PET Imaging: A Pilot Study.","authors":"Ali Ahmadi, Ran Klein, David Gao, Lisa M Mielniczuk, Jason G E Zelt, Kevin E Boczar, Rob S Beanlands, Paco E Bravo, Yuchi Han, Marcelo F Di Carli, Robert A deKemp","doi":"10.1007/s11307-025-01987-5","DOIUrl":"https://doi.org/10.1007/s11307-025-01987-5","url":null,"abstract":"<p><strong>Purpose: </strong>¹¹C-acetate PET is used to measure biventricular oxygen myocardial consumption rate (MVO₂) and myocardial blood flow (MBF) changes associated with right ventricular (RV) remodelling. We studied PET reproducibility and repeatability for such RV assessments.</p><p><strong>Procedures: </strong>10 pulmonary hypertension (PH) patients underwent ¹¹C-acetate PET. Five of these patients also had a repeat scan after 26 ± 2 weeks. A one-tissue compartment model was used to measure the myocardial tissue-activity washout rate (k2 [1/min] for MVO₂ estimation) and the blood-to-tissue activity flux (K1 [1/min] for MBF calculation). Values were measured by 2 blinded observers and analyzed by ANOVA and Bland-Altman tests. The interquartile ranges (IQR), within-subject coefficients of variation (wCV), and intraclass correlation coefficients (ICC) were reported.</p><p><strong>Results: </strong>All patients had stable PH with the clinical assessments showed comparable biventricular function and size between baseline and follow-up. The k2-derived MVO₂ and K1-derived MBF values were consistently higher in the LV than RV. The high inter- and intra-observer reproducibility (for biventricular MVO₂ and MBF) was indicated by low IQR (≤ 7.6%) and wCV (≤ 8%) as well as high ICC (≥ 95%). The test-retest (baseline to follow-up) repeatability showed larger IQR (≤ 35.4%) and wCV (≤ 29%) but consistently high ICC (= 95%).</p><p><strong>Conclusions: </strong>MVO₂ and MBF values measured in the RV of patients with PH were highly reproducible and repeatable. This can help inform the design of clinical research studies using serial ¹¹C-acetate PET imaging to evaluate RV metabolism.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408261","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":"Optical-magnetic Imaging for Optimizing Lymphodepletion-TIL Combination Therapy in Breast Cancer.","authors":"Jiaqian Li, Lishuang Guo, Yuan Feng, Guanghui Li, He Sun, Wei Huang, Jie Tian, Yang Du, Yu An","doi":"10.1007/s11307-025-01985-7","DOIUrl":"https://doi.org/10.1007/s11307-025-01985-7","url":null,"abstract":"<p><strong>Purpose: </strong>Lymphodepletion before tumor-infiltrating lymphocytes (TIL) infusion can activate the immune system, enhance the release of homeostatic cytokines, and decrease the number of immunosuppressive cells. This process is crucial for improving the therapeutic efficacy of TIL therapy. However, the challenge of in vivo assessing TILs targeting tumors limits the optimization of lymphodepleting conditioning regimen (LDC).</p><p><strong>Procedures: </strong>This study aims to employ magnetic particle imaging (MPI) and fluorescence molecular imaging (FMI) to monitor TIL biodistribution in vivo and optimize LDC in triple-negative breast cancer TIL therapy. MPI provides quantitative imaging capabilities without depth limitations, effectively complementing the high sensitivity of FMI. The efficacy of different LDCs in enhancing TIL therapy was assessed using FMI, and MPI quantified the number of TILs accumulated in the 4T1 tumor.</p><p><strong>Results: </strong>TILs preserved viability, phenotypes, and anti-tumor efficacy after being labeled with superparamagnetic iron oxide and fluorescence dye DiR. The dual-modality imaging system effectively discerned variations in LDC treatments that enhanced TIL therapy. Compared to TIL monotherapy, lymphodepletion with TIL therapy improves tumor dual-modality imaging signal intensity, increases the expression of monocyte chemotactic protein-1 in serum and tumor tissue, and enhances the therapeutic effect of TILs.</p><p><strong>Conclusion: </strong>Our results confirm the utility of optical-magnetic dual-modality imaging for tracking the biodistribution of TILs in vivo. With the help of optical-magnetic dual-modality imaging, we successfully optimize TIL combination therapy. Optical-magnetic dual-modality imaging provides a new approach to develop personalized immunotherapy strategies and mine potential therapeutic mechanisms for TIL.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255947","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":"DCE-MRI Detects OATP-expressing Transplanted Cells Using Clinical Doses of Gadolinium Contrast Agent.","authors":"Tapas Bhattacharyya, Christiane L Mallett, Jeremy M-L Hix, Erik M Shapiro","doi":"10.1007/s11307-025-01986-6","DOIUrl":"https://doi.org/10.1007/s11307-025-01986-6","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatic organic anion transporting polypeptides (OATPs) transport off-the-shelf, FDA-approved, hepatospecific Gd-based MRI contrast agents into cells that express the transporters enhancing signal on T1-weighted MRI. Studies have used MRI to identify OATP-overexpressing tumors and metastases transplanted in mice following the delivery of Gd-EOB-DTPA at 27-67-fold higher than clinical doses. With safety and regulatory concerns over Gd-based contrast agents, translating OATPs as an MRI reporter protein to humans for regenerative medicine will require substantially lower doses of agent.</p><p><strong>Procedures: </strong>We engineered the MyC-CaP mouse tumor cell line to express rat OATP1B2, which influxes both Gd-EOB-DTPA and Gd-BOPTA, resulting in signal enhancement on T1-weighted MRI. We then inoculated mice with rat OATP1B2 and non-expressing cells bilaterally to generate tumors. 3-4 weeks after inoculation, when tumors had formed, in-vivo MRI imaging was performed with delivery of 0.025 mmol/kg or 0.25 mmol/kg of the Gd-based contrast agents. We complemented static T1-weighted MRI and T1-mapping with dynamic contrast enhanced (DCE)-MRI and performed area under the curve (AUC) analysis to discriminate the two tumor types.</p><p><strong>Results: </strong>While all OATP1B2-expressing tumors were easily visible at the high dose of 0.25 mmol/kg on T1-weighted MRI and easy to distinguish from control tumors, OATP1B2-expressing tumors were hard to identify and distinguish from non-expressing tumors at the lower, clinical dose of 0.025 mmol/kg with standard T1-weighted MRI or T1-mapping. However, AUC analyses of the DCE-MRI curves could identify and distinguish these tumors, needing 30 (Gd-EOB-DTPA) or 45 (Gd-BOPTA) minutes acquisition time.</p><p><strong>Conclusions: </strong>By performing AUC analyses of DCE-MRI curves following delivery of clinical concentration of MRI contrast agents, OATP1B2-expressing tumors could be identified and distinguished from control tumors, suggesting this imaging approach as a path to substantially reducing the amount of contrast agent needed to use OATPs as a clinically viable reporter protein for imaging regenerative medicine.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189782","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}