Molecular Imaging and Biology最新文献

{"title":"Development and Evaluation of a Vinyl Sulfone-Based Fluorine-18 Labeling Method for Constructing PSMA-targeted Prostate Cancer Imaging Agents.","authors":"Changjiang Wang, Ruiling Long, Mei Hu, Liu Zhou, Haoyuan Ding, Weiling Zhao, Zhanwen Huang, Yue Chen, Zibo Li, Li Wang","doi":"10.1007/s11307-025-02036-x","DOIUrl":"https://doi.org/10.1007/s11307-025-02036-x","url":null,"abstract":"<p><strong>Purpose: </strong>Since prostate-specific membrane antigen (PSMA) is widely expressed in nearly all stages of prostate cancer (PCa), PSMA tracers can be considered a viable diagnostic tool for PCa. Compared to ⁶⁸Ga-labeled PSMA agents, ¹⁸F-labeled analogues have various advantages, including the ability to achieve large scale production; easy to commercialize due to its longer half-life; and the ability to image late time points. Because [¹⁸F]vinyl sulfone (VS) is a good intermediate for labeling thiol groups in mild conditions with high labeling yield, we explored the use of various VS groups for PSMA modifications in this study.</p><p><strong>Procedures: </strong>We developed six ¹⁸F-labeled radiotracers targeting PSMA from radioactive intermediates to explore targeting ability and distribution in vivo in LNCaP and 22RV1 tumor-bearing mice. Different labeling methods were compared on their ability to lead to PSMA agents with high contrast and uptake.</p><p><strong>Results: </strong>In vitro stability assay showed that the tracer [¹⁸F]4a had high stability, with more than 95% of the radiochemical purities remaining as intact forms after 0.5, 1, and 2 h incubation, respectively. In vitro binding assays showed that [¹⁸F]4a has a low-micromole binding affinity of 9.45 µM. Cell uptake and internalization assays found that [¹⁸F]4a exhibited the highest cell uptake and internalization in 22RV1 cells (1.25 ± 0.06, 1.32 ± 0.11, 1.73 ± 0.08, and 2.03 ± 0.14%ID/10⁶ cells after 10 min, 30 min, 1 h, and 2 h incubation, respectively for cell uptake assay; 0.52 ± 0.02, 0.70 ± 0.11, 0.78 ± 0.04, and 0.98 ± 0.15%ID/10⁶ cells after 10 min, 30 min, 1 h, and 2 h incubation, respectively for cell internalization assay.) Analysis of the PET images showed that the tracer [¹⁸F]4a had the highest tumor uptake (3.38 ± 0.35%ID/g at 2 h p. i. in 22RV1 tumor-bearing mice; 30.16 ± 13.00%ID/g at 2 h p. i. in LNCaP tumor-bearing mice.) Of note, the tracer [¹⁸F]4a showed an approximately threefold increase in tumor uptake compared to [⁶⁸Ga]PSMA-11 in LNCaP tumor-bearing mice at 2 h p. i. The biodistribution experiment verified the accuracy of the in vivo distribution of [¹⁸F]4a in LNCaP and 22RV1 tumor-bearing mice by PET/CT imaging.</p><p><strong>Conclusions: </strong>PSMA-targeted radiotracer [¹⁸F]4a is a promising PET agent for prostate cancer diagnosis.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718194","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":"Preclinical Evaluation of Novel SGLT2-Targeted Near-Infrared Optical Imaging Agent for Early-Stage Pulmonary Adenocarcinoma.","authors":"Katherine Ortmeyer Welch, Kelly Anne McGovern, Lydia Chen, Ryan Krouse, Kevin Guo, Jeffrey Huang, Michael Brown, Jake Mlakar, Venu Bandi, David Holt, Paul Zhang, Sunil Singhal","doi":"10.1007/s11307-025-02029-w","DOIUrl":"https://doi.org/10.1007/s11307-025-02029-w","url":null,"abstract":"<p><strong>Purpose: </strong>Lung cancer is increasingly diagnosed at early stages, but intraoperative localization of early lesions remains challenging. Intraoperative molecular imaging (IMI) aids in localization of tumors during surgery; however, no optical agents are targeted specifically for early-stage lesions. The sodium-glucose cotransporter 2 (SGLT2) has been implicated in early lung carcinogenesis. This study aimed to describe SGLT2 expression in early-stage lung adenocarcinoma (LUAD) and develop and validate a novel SGLT2-targeted near-infrared (NIR) contrast agent, GlucoGlo, for imaging LUAD.</p><p><strong>Procedures: </strong>SGLT2 expression was confirmed by immunohistochemistry (IHC) in human samples. GlucoGlo optical properties were characterized and compared to common NIR dyes. Sensitivity and specificity for SGLT2 were assessed using preclinical in vitro and in vivo mouse models.</p><p><strong>Results: </strong>On IHC, stage I LUAD displayed higher SGLT2 expression than stage II-III LUAD and normal lung tissue. GlucoGlo exhibited similar depth of penetration and resolution to FDA-approved contrast agents. SGLT2-expressing cell lines treated with GlucoGlo displayed higher fluorescence than the control cell line, confirming SGLT2-dependent uptake. Fluorescence increased with both incubation time and GlucoGlo concentration. Glucose and unconjugated GlucoGlo ligand competitively inhibited GlucoGlo in a dose-dependent manner, indicating high affinity and specificity. GlucoGlo selectively accumulated in SGLT2-expressing flank xenografts, with mean SBR of 2.23 and was inhibited by pretreatment with unconjugated GlucoGlo ligand.</p><p><strong>Conclusions: </strong>These findings support the potential of GlucoGlo as a targeted IMI contrast agent for early-stage LUAD, and they provide a foundation for future in vivo studies and translational development.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637663","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":"Local Infusing Antiplatelet Microspheres to Prevent Thrombosis Post-PCI: a Feasibility Study in Rabbit Aorta.","authors":"Yueyou Peng, Kunkun Liu, Wei Tian, Tianfeng Shi, Qixiong Lin, Yanmei Tian, Rongrong Li, Yanfeng Meng","doi":"10.1007/s11307-025-02032-1","DOIUrl":"https://doi.org/10.1007/s11307-025-02032-1","url":null,"abstract":"<p><strong>Purpose: </strong>After percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is required to prevent thrombosis, but systemic DAPT may increase bleeding risk. This study aimed to develop a new concept of antiplatelet therapy administered via local infusion of PLGA-Fe₃O₄-ticagrelor microspheres (PFTm).</p><p><strong>Procedures: </strong>PLGA loaded with Fe₃O₄ and ticagrelor magnetic microspheres were constructed. In vitro study, the morphology, relaxation rate, drug release rate, encapsulation efficiency, and biocompatibility of PFTm were evaluated. In vivo study, vascular injury model of rabbit abdominal aorta was established by Fogarty balloon. The injured rabbit aorta wall was infused PFTm by infusion balloon in the local PFTm therapy group, while the rabbit was injected PFTm intravenously in the systemic PFTm therapy group. The non-therapy control group and healthy control group did not receive PFTm treatment. MR T2WI was performed pre-operation, post-operation to detect PFTm distribution. Then, the targeted abdominal aorta segments were harvest for pathological examination.</p><p><strong>Results: </strong>The PFTm was spherical with a size of 930.5 ± 134 nm and SPAN was 0.35. The ticagrelor encapsulation efficiency was 82% ± 2%, and the release rate reached 88% ± 2% within 96 h. The r2 of the PFTm was 332.0 mM^-1 s^-1. All rabbits were successfully established abdominal aorta injury model. MRI showed significant decrease of SNR in aortic wall which represented PFTm infused into aortic wall. Pathology showed that local thrombus was significant inhibited in the local PFTm therapy group compared with the other groups.</p><p><strong>Conclusions: </strong>The new concept of releasing drugs in a sustained manner for local antiplatelet therapy after PCI was successfully established.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601004","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":"Combining Dopamine Transporter and Amyloid PET Tracer: A Preclinical Study on Dual-Target Imaging.","authors":"Bok-Nam Park, Su-Min Kim, Young-Sil An","doi":"10.1007/s11307-025-02033-0","DOIUrl":"https://doi.org/10.1007/s11307-025-02033-0","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the feasibility and diagnostic utility of a dual-target positron emission tomography (PET) imaging approach using a cocktail of N-3-[¹⁸F]fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([¹⁸F]FP-CIT) and [¹⁸F]florbetaben (FBB) for the simultaneous assessment of dopaminergic and amyloid changes in a preclinical setting.</p><p><strong>Procedures: </strong>We utilized both Parkinson's disease (PD) and Alzheimer's disease (AD) mouse models, as well as a control group, to investigate the uptake of [¹⁸F]FP-CIT and [¹⁸F]FBB individually and in combination. PET imaging was conducted, and standardized uptake value ratios (SUVRs) were analyzed for each model across the striatal and cortical regions. Comparisons were made between single and cocktail PET scans to assess potential cross-interference of the tracers.</p><p><strong>Results: </strong>In both PD and AD models, no statistically significant differences were observed in the SUVRs between single-tracer and cocktail PET scans in the striatum and cortex (p > 0.4 for striatal comparisons, p > 0.8 for cortical comparisons). Bland-Altman analysis showed no significant bias, supporting the interchangeability of SUVRs between single and cocktail PET scans.</p><p><strong>Conclusions: </strong>This preclinical study suggests that [¹⁸F]FP-CIT and [¹⁸F]FBB PET imaging is a viable dual-target imaging approach for neurodegenerative disease evaluation. The method could streamline diagnostic workflows and improve patient convenience. Further clinical studies are warranted to validate the efficacy and safety of this approach in human populations.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591758","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":"¹⁹F MR Imaging of Dule Lung Cancer Models with Two Administration Methods of PFC Nanoparticles.","authors":"Fang Liu, Mengping Shao, Xiuan Xu","doi":"10.1007/s11307-025-02034-z","DOIUrl":"https://doi.org/10.1007/s11307-025-02034-z","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary delivery of agents to lung is an effective method for the diagnosis and therapy of lung cancer.</p><p><strong>Purpose: </strong>To demonstrate that pulmonary delivery of perfluorocarbon (PFC) nanoparticles for orthotopic lung tumor model is better than intravenous injection for subcutaneous tumor, and to confirm that the nanoparticles can be uptaked by tumor tissue which showed by ¹⁹F MR imaging and tissue staining.</p><p><strong>Methods: </strong>We detected the targeted ability of folate receptor (FR) targeted PFC nanoparticles with H460 cells in vitro. Subcutaneous and orthotopic lung cancer models were established. When the tumors could be detected by MR after two weeks, PFC nanoparticles were administrated intratracheally in orthotopic group and intravenously in subcutaneous group. ¹⁹F MR scanning was performed in mice models at before and different time points (4, 24, and 48 h) after delivery. Mice were euthanized after MR imaging, and tumor tissues were taken out, HE and fluorescent staining were performed respectively. In addition, orthotopic tumor tissue was obtained for transmission electron microscopy (TEM) examination.</p><p><strong>Results: </strong>The orthotopic tumor model showed a significant ¹⁹F MRI enhancement effect in the tumor region after PFC nanoparticles delivered intratracheally than subcutaneous model. As time went on, the accumulation of nanoparticles in the tumor area increased, and the ¹⁹F signal increased gradually. The ¹⁹F SNR in the tumor region of orthotopic group was significantly higher than that of subcutaneous group at 24 and 48 h after delivery (p < 0.001). Histological experiments showed that PFC nanoparticles accumulated in the tumor region especially in orthotopic group.</p><p><strong>Conclusion: </strong>Pulmonary delivery of PFC nanoparticles is a novel and effective method for orthotopic lung cancer xenograft model, and the PFC nanoparticles can be detected by ¹⁹F MR imaging in vivo.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591757","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":"Positive Protective Effects of Sigma-1 Receptor Stimulation with Fluvoxamine after Myocardial Ischemia and Reperfusion in Rats.","authors":"Xue Zhang, Hiroshi Wakabayashi, Hiroshi Mori, Tomo Hiromasa, Zhuoqing Chen, Takashi Kozaka, Kazuma Ogawa, Seigo Kinuya, Junichi Taki","doi":"10.1007/s11307-025-02030-3","DOIUrl":"https://doi.org/10.1007/s11307-025-02030-3","url":null,"abstract":"<p><strong>Background: </strong>The sigma-1 receptor (Sig-1R) plays diverse roles in regulating Endoplasmic Reticulum (ER) stress, calcium handling, and ion channel activity under pathological conditions, offering cardioprotective effects in pressure overload-induced dysfunction. However, its role in post-myocardial ischemia damage remains unclear. This study evaluated the cardioprotective effects of Sig-1R activation by fluvoxamine following myocardial ischemia in rats.</p><p><strong>Method and results: </strong>Wistar rats underwent 20 min of coronary artery occlusion followed by reperfusion. Rats received either saline (control) or fluvoxamine for two weeks. ECG-gated SPECT with ^99mTc-MIBI was performed on days 1, 14, and 28 post-reperfusion to measure the end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), and summed rest score (SRS). Autoradiography and histological analyses were performed on day 29. Fluvoxamine significantly improved LVEF after two weeks (D14-D1: 6 ± 7, p = 0.03), with the improvement persisting to the 28th day (8 ± 5, p < 0.01). Autoradiography revealed a smaller non-salvaged area (0.15 ± 0.19 vs. 0.42 ± 0.32, p < 0.05) and more salvaged myocardium (0.33 ± 0.13 vs. 0.14 ± 0.14, p < 0.05) in the fluvoxamine group. Histology showed less fibrosis (0.06 ± 0.05 vs. 0.11 ± 0.08, p < 0.05) and reduced macrophage infiltration (0.08 ± 0.05 vs. 0.16 ± 0.08, p < 0.001) with fluvoxamine.</p><p><strong>Conclusions: </strong>Sig-1R stimulation by fluvoxamine suppresses LV remodelling and enhances LVEF recovery post-ischemia, suggesting its potential as a novel cardioprotective strategy.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560528","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":"MIB guides: [⁸⁹Zr]Zr-DFO-trastuzumab and [⁶⁴Cu]Cu-NOTA-Trastuzumab for Preclinical Cancer Imaging.","authors":"Cristina Simó, Alexander C Vanover, E Carmen Azevedo, Patrícia M R Pereira","doi":"10.1007/s11307-025-02022-3","DOIUrl":"10.1007/s11307-025-02022-3","url":null,"abstract":"<p><p>Radiopharmaceuticals based on antibody biomolecules are widely used in oncology for positron emission tomography (PET). Trastuzumab, an antibody that targets the epidermal growth factor receptor 2 (HER2), has been extensively studied for both preclinical and clinical cancer imaging. This MIB guide specifically focuses on the radiolabeling of the antibody trastuzumab with zirconium-89 (⁸⁹Zr) and copper-64 (⁶⁴Cu) for PET imaging. The guide describes the steps for conjugating trastuzumab with p-SCN-Bn-deferoxamine (DFO) or 2,2',2''-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (p-SCN-Bn-NOTA) chelators through conjugation between the isothiocyanate (-SCN) functional group on the chelator with lysines on the trastuzumab. We also describe subsequent radiolabeling steps with ⁸⁹Zr or ⁶⁴Cu. The steps described here can be adapted to the radiolabeling of other antibodies upon protocol optimization.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506839","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":"Diagnostic Value of [¹⁸F]-FDG and [⁶⁸ Ga]-FAPI-04 PET/MRI for Lymph Node Metastasis in Papillary Thyroid Cancer.","authors":"Tingting Han, Zhiyong Quan, Hongliang Wei, Mingru Zhang, Jiajun Ye, Guiyu Li, Junling Wang, Taoqi Ma, Jing Wang, Fei Kang","doi":"10.1007/s11307-025-02028-x","DOIUrl":"https://doi.org/10.1007/s11307-025-02028-x","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the diagnostic value of [¹⁸F]-FDG PET/MRI for the diagnosis of neck lymph node metastasis (LNM) in patients with initially diagnosed papillary thyroid cancer (PTC) and to compare it with [⁶⁸ Ga]-FAPI-04 PET/MRI.</p><p><strong>Methods: </strong>Thirty patients with PTC confirmed by thyroid fine-needle aspiration biopsy were prospectively enrolled and underwent [¹⁸F]-FDG PET/MRI; of which, 6 additionally underwent [⁶⁸ Ga]-FAPI-04 PET/MRI within 3 days. According to surgical guidelines, the neck lymph node (LN) was divided into three macroscopic regions: central (VI) and left/right lateral neck (II-V). Images were semi-quantitatively and visually interpreted, and lesions' quantity, location, and uptake values were noted. Diagnostic performance of [¹⁸F]-FDG PET/MRI versus US and MRI in N-staging of PTC patients based on regional analysis using postoperative histopathology as the gold standard. Whether the BRAF_V600E mutation or not affects metastatic LN radioactivity uptake. Exploring the relevance of dual tracer imaging of metastatic LN radioactivity uptake and its head-to-head comparison for diagnostic efficacy.</p><p><strong>Results: </strong>A total of 48 macroscopic regions were surgically dissected. In terms of predicting LNM, the diagnostic efficacy of [¹⁸F]-FDG PET/MRI for detecting LNM was higher than that of US and MRI, overall sensitivity, specificity, and accuracy were 71.1% vs. 60.5% vs. 65.8%, 90.0% vs.80.0% vs. 80.0%, and 75.0% vs. 64.6% vs. 68.8%, respectively (all P > 0.05). SUV_max of metastatic LNs on [⁶⁸ Ga]-FAPI-04 PET/MRI was positively correlated with [¹⁸F]-FDG PET/MRI (r = 0.8564, 95%CI: 0.7208-0.9289; P < 0.0001). BRAF_V600E mutation had no significant effect on the [¹⁸F]-FDG uptake level and TBR value in metastatic LN of PTC (SUV_max: 2.5 ± 2.3 vs. 2.2 ± 1.1; TBR: 2.9 ± 2.6 vs. 2.6 ± 1.4; all P > 0.05). The positive lesion detection rate of dual tracer imaging in 6 patients with PTC is consistent, and the degree of radioactivity uptake of [⁶⁸ Ga]-FAPI-04 was higher than that of [¹⁸F]-FDG in both primary lesion and LNM (12.3 ± 5.7 vs. 6.9 ± 5.3;4.5 ± 3.7 vs. 3.4 ± 1.8; all P > 0.05).</p><p><strong>Conclusion: </strong>[¹⁸F]-FDG PET/MRI demonstrated marginally superior diagnostic performance for LNM detection compared to US and MRI, but all three modalities exhibited suboptimal sensitivity, particularly in the central region. Small sample populations revealed no significant differences in [⁶⁸ Ga]-FAPI-04 and [¹⁸F]-FDG uptake levels in primary lesion and LNM of PTC, but relatively lower nonspecific uptake of [⁶⁸ Ga]-FAPI-04 pharyngeal lymphatic ring may have the potential to reduce diagnostic error in specific diseases.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485124","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":"Poor Diagnostic Performance of the Melanin-Binding Tracer [18 F]MEL050 in Human Melanoma Indicates Biological Heterogeneity.","authors":"Robert E Ware, Damien Kee, Peter Roselt, Ivan Greguric, Andrew Katsifis, Thomas Bourdier, Wayne Noonan, William Murray, Catherine Mitchell, Marnie Downes, Mark Shackleton, Grant A McArthur, Rodney J Hicks","doi":"10.1007/s11307-025-02025-0","DOIUrl":"10.1007/s11307-025-02025-0","url":null,"abstract":"<p><strong>Purpose: </strong>Malignant melanoma is a highly lethal malignancy typically characterized by the expression of melanin, which is an attractive diagnostic and therapeutic target in these cancers because it is expressed in few other tissues. Following preclinical evaluation of the melanin-targeting PET tracer, [18F]-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide ([18F]MEL050), we sought to evaluate this agent in patients with melanoma.</p><p><strong>Method: </strong>A phase I clinical trial was performed in ten patients with metastatic melanoma. Safety, dosimetry and diagnostic performance of intravenously administered][18F]MEL050 were evaluated. Based on results from this trial, we further assessed the prevalence and prognostic significance of loss of melanin expression in two historical patient cohorts for which there were matching histological and clinical outcome data.</p><p><strong>Results: </strong>Across the trial cohort, no adverse safety signals resulted from [18F]MEL050 administration. The whole-body effective dose was 0.0163 mSV/MBq for an adult male and 0.0206 mSV/MBq for an adult female. The human biodistribution was favorable with low uptake in organs at high risk of metastatic spread, including the brain. Of metastatic sites identified as melanoma on [18F]FDG PET/CT, only 31/65 (48%) were positive on [18F]MEL050 PET. Four [18F]FDG+[18F]MEL050+ metastases were resected from three patients and found to be melanotic by histological examination, whereas five [18F]FDG+[18F]MEL050- metastases from two patients were amelanotic. In our historical cohorts, amelanosis was more common in metastatic than primary disease (45% versus 20%) and the presence of melanin within sentinel lymph node metastases was associated with worse disease-free (HR 2.3 95% CI 1.3 - 4.3, p = 0.002) and disease-specific survivals (HR 3.6, 95% CI 1.4 - 9.7,p = 0.009) in stage III disease, compared with amelanotic sentinel lymph node metastases.</p><p><strong>Conclusion: </strong>We propose caution in the use of melanin-targeted agents for melanoma diagnosis and therapy until their utility as prognostic or predictive imaging biomarkers, and the biological implications of loss of melanin deposition during melanoma progression, are better understood.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333519","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":"Preclinical Evaluation of a Near-Infrared Labelled Antibody Targeting the Tumour Associated Xenoantigen N-Glycolyl-Neuraminic Acid GM3 Ganglioside.","authors":"Kris Barreto, Wendy Bernhard, Darien Toledo, Kimberly Jett, Angel Casaco, Kalet León, C Ronald Geyer","doi":"10.1007/s11307-025-02026-z","DOIUrl":"https://doi.org/10.1007/s11307-025-02026-z","url":null,"abstract":"<p><strong>Purpose: </strong>Targeted and broadly applicable molecular targets are important for image guided surgery. Xenoantigens represent a particularly interesting class of targets. This study evaluates the xenoantigen N-glycolyl-neuraminic acid GM3 ganglioside (Neu5Gc-GM3) as a potential fluorescence-guided surgical tool.</p><p><strong>Procedures: </strong>The antibody 14F7hT is conjugated to the near-infrared dye (IRDye800CW) and characterized under GLP conditions. The quality and stability of the 14F7hT-IRDye800CW probe was assessed. In vivo imaging using 14F7hT-IRDye800CW in mice with Neu5Gc GM3 positive and negative xenografts were compared to a control IgG-IRDye800CW probe targeting an epitope not present on the xenografts. Biodistribution, pharmacokinetics, and toxicity were evaluated.</p><p><strong>Results: </strong>The 14F7hT-IRDye800CW probe was 98 ± 2% pure as determined by micro-capillary electrophoresis. The KDapp as determined by binding cell-lines expressing the target was unchanged after conjugation. We demonstrate a peak accumulation window of 12 - 48 h in murine xenografts with male and female CD-1 nude mice administered 0.5 nmoles of the probe (i.v.) and very low uptake in other tissues. Preclinical toxicity studies in male and female balb/c mice support a no observed adverse effect level (NOAEL) of 50 mg/kg in mice.</p><p><strong>Conclusions: </strong>The 14F7hT-IRDye800CW probe was found to be safe and have low non-specific uptake in a model organism known to express the target. These data support future clinical development of the probe.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317486","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}