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Pharmacokinetic Modeling of Hepatospecific MRI Contrast Agent Flux in Large Animal Models by Dynamic Contrast-Enhanced MRI. 大动物模型肝特异性MRI造影剂通量的动态增强MRI药代动力学建模。
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-07-20 DOI: 10.1007/s11307-026-02117-5
Matthew T Latourette, Jeremy M L Hix, Jie Huang, Christiane L Mallett, Kirk A Muñoz, Erik M Shapiro
{"title":"Pharmacokinetic Modeling of Hepatospecific MRI Contrast Agent Flux in Large Animal Models by Dynamic Contrast-Enhanced MRI.","authors":"Matthew T Latourette, Jeremy M L Hix, Jie Huang, Christiane L Mallett, Kirk A Muñoz, Erik M Shapiro","doi":"10.1007/s11307-026-02117-5","DOIUrl":"10.1007/s11307-026-02117-5","url":null,"abstract":"<p><strong>Purpose: </strong>Evaluate the feasibility of using dogs and a pig as translational models for assessing hepatic flux of hepatospecific gadolinium-based contrast agents using dynamic contrast-enhanced MRI (DCE-MRI).</p><p><strong>Procedures: </strong>DCE-MRI was performed with hepatospecific agents, gadoxetate disodium (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA), and non-hepatospecific agents. Two validated pharmacokinetic models were applied: a single-input reference region model and a dual-input model using arterial and venous blood signals.</p><p><strong>Results: </strong>In dogs, hepatic enhancement rose rapidly and plateaued after Gd-EOB-DTPA administration, with minimal decline over an hour. In the pig, both hepatospecific agents showed a rapid rise, blunt peak, and gradual decline. The single-input model revealed significantly higher uptake rates for hepatospecific agents, confirming its sensitivity to hepatocyte uptake. The dual-input model effectively distinguished contrast agent dynamics in dogs and showed promise in the pig.</p><p><strong>Conclusions: </strong>In this feasibility study, the enhancement dynamics observed and pharmacokinetic estimates computed in both dogs and a pig fell broadly within ranges reported in human studies, supporting their potential utility as translational large-animal models. Definitive comparison of species similarity to humans will require direct paired evaluation under matched conditions.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536509","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}
引用次数: 0
Correction: Sonodynamic Therapy-Enhanced Immunotherapy for Triple-Negative Breast Cancer: Mechanistic Advances, Nanoplatform Strategies, and Clinical Prospects. 修正:声动力疗法增强免疫疗法治疗三阴性乳腺癌:机制进展、纳米平台策略和临床前景。
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-07-15 DOI: 10.1007/s11307-026-02123-7
Ramanjireddy Tatiparthi, Ansuman Panda, Mvnl Chaitanya, Fanta Gashe, Gemmechu Hasen, Raghavendra Yarlagadda
{"title":"Correction: Sonodynamic Therapy-Enhanced Immunotherapy for Triple-Negative Breast Cancer: Mechanistic Advances, Nanoplatform Strategies, and Clinical Prospects.","authors":"Ramanjireddy Tatiparthi, Ansuman Panda, Mvnl Chaitanya, Fanta Gashe, Gemmechu Hasen, Raghavendra Yarlagadda","doi":"10.1007/s11307-026-02123-7","DOIUrl":"10.1007/s11307-026-02123-7","url":null,"abstract":"","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456402","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}
引用次数: 0
FcRn-Targeted Alpha Therapy Using [225Ac]Ac-Macropa-Rozanolixizumab Enables Potent Antitumor Activity. 使用[225Ac]Ac-Macropa-Rozanolixizumab进行fcrn靶向α治疗具有有效的抗肿瘤活性
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-07-15 DOI: 10.1007/s11307-026-02124-6
Saba Shirin, Syed Qaiser Shah, Ralph Santos-Oliveira
{"title":"FcRn-Targeted Alpha Therapy Using [<sup>225</sup>Ac]Ac-Macropa-Rozanolixizumab Enables Potent Antitumor Activity.","authors":"Saba Shirin, Syed Qaiser Shah, Ralph Santos-Oliveira","doi":"10.1007/s11307-026-02124-6","DOIUrl":"https://doi.org/10.1007/s11307-026-02124-6","url":null,"abstract":"<p><strong>Purpose: </strong>Overexpression of FcRn in multiple hematologic and solid cancers makes it a promising target for monoclonal antibodies, though its presence in healthy tissue calls for proper assessment of toxicity. Here, we report the preclinical development and evaluation of [<sup>225</sup>Ac]Ac-Macropa-rozanolixizumab, a proof-of-concept FcRn-targeted α-radioimmunotherapeutic.</p><p><strong>Procedure: </strong>Using a site-specific approach based on interchain disulfide re-bridging, rozanolixizumab was conjugated with Macropa by a PEG<sub>4</sub> linker and radiolabeled with actinium-225 in mild aqueous conditions. FcRn binding, immunoreactivity and cytotoxicity were assessed in vitro. Following a single dose administration, biodistribution, dosimetry, and antitumor activity were studied in CHO-FcRn xenograft-bearing mice.</p><p><strong>Results: </strong>Conjugation produced a homogeneous product (chelator-to-antibody ratio 3.3 ± 0.2; > 96% monomer). FcRn binding was retained following conjugation and radiolabeling, although affinity was reduced relative to native rozanolixizumab (K<sub>d</sub> = 3.77 ± 0.86 nM). The immunoreactive fraction was 82.4 ± 3.1%. Radiolabeling efficiency was 98.9 ± 0.8% and serum stability exceeded 94% at 168 h. Receptor-dependent cytotoxicity was confirmed in vitro (IC<sub>50</sub> = 4.86 ± 0.4 kBq/mL in FcRn-positive cells), with minimal effect in FcRn-negative controls. Tumor uptake peaked at 20.3 ± 1.9%ID/g at 48 h with low skeletal uptake. Absorbed dose ratios were 4.82/0.28 Gy/MBq (tumor/bone marrow; ratio 17.2). A single treatment produced significant survival benefit (log-rank P < 0.001), dose-dependent tumor control, and transient, self-limiting body weight changes.</p><p><strong>Conclusions: </strong>[<sup>225</sup>Ac]Ac-Macropa-rozanolixizumab demonstrated FcRn-specific α-particle cytotoxicity and favorable dosimetric properties in a proof-of-concept xenograft model. These findings support FcRn as a potential target for radioimmunotherapy. Further studies are required to evaluate toxicity, endogenous IgG competition and translational applicability.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456330","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}
引用次数: 0
Collagen-binding ⁶⁸Ga-CBP8 PET/MR in Deep Pelvic Endometriosis: First-in-human Application. 胶原结合⁶⁸Ga-CBP8 PET/MR在深盆腔子宫内膜异位症中的首次应用。
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-07-14 DOI: 10.1007/s11307-026-02125-5
Antonino Andrea Blandino, Peter Caravan, Anuradha S Shenoy-Bhangle, Peter R Movilla, Elio Quiros, Mario V Russo, Michael J Misialek, Liran Domachevsky, Leo L Tsai, Onofrio Antonio Catalano
{"title":"Collagen-binding ⁶⁸Ga-CBP8 PET/MR in Deep Pelvic Endometriosis: First-in-human Application.","authors":"Antonino Andrea Blandino, Peter Caravan, Anuradha S Shenoy-Bhangle, Peter R Movilla, Elio Quiros, Mario V Russo, Michael J Misialek, Liran Domachevsky, Leo L Tsai, Onofrio Antonio Catalano","doi":"10.1007/s11307-026-02125-5","DOIUrl":"10.1007/s11307-026-02125-5","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the feasibility of collagen-binding ⁶⁸Ga-CBP8 PET/MR for the noninvasive detection of deep infiltrating endometriosis.</p><p><strong>Material and methods: </strong>A single-case exploratory application of ⁶⁸Ga-CBP8 PET/MR was conducted in a patient with endometriosis as a preliminary step toward a larger IRB-approved prospective study. Imaging was performed 60 min after intravenous administration of ⁶⁸Ga-CBP8. Fused PET/MR images were qualitatively assessed for focal tracer uptake exceeding background. Surgical pathology, assessed in a blinded fashion, served as the reference standard.</p><p><strong>Results: </strong>A 32-year-old woman with history of endometriosis completed the examination without adverse events. PET/MR demonstrated focal ⁶⁸Ga-CBP8 uptake corresponding on MR to a T2-hypointense plaque located between the left adnexa and the sigmoid colon, suspicious for deep pelvic endometriosis with bowel involvement. Surgical pathology confirmed endometriosis infiltrating the colonic muscularis mucosae and pericolonic tissue with dense fibrosis.</p><p><strong>Conclusion: </strong>⁶⁸Ga-CBP8 PET/MR is a feasible and promising technique to noninvasively detect deep infiltrating endometriosis, warranting validation in larger prospective studies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT06377553. Date of first enrollment: February 5, 2025. Registered April 22, 2024.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448043","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}
引用次数: 0
Cross-Species Quantitative Benchmarking of SSTR2 Radioligands in Fresh-Frozen Brain Sections: An Adaptable Framework for Radiopharmaceutical Development. 新鲜冷冻脑切片中SSTR2放射性配体的跨物种定量基准:放射性药物开发的适应性框架。
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-07-09 DOI: 10.1007/s11307-026-02113-9
Caitlin McCutcheon, Zachary Lawrence, Marie James, Taryn Palluccio, Maha Chowdhury, Pradeep K Singh, Kelly Orcutt, Shil Patel
{"title":"Cross-Species Quantitative Benchmarking of SSTR2 Radioligands in Fresh-Frozen Brain Sections: An Adaptable Framework for Radiopharmaceutical Development.","authors":"Caitlin McCutcheon, Zachary Lawrence, Marie James, Taryn Palluccio, Maha Chowdhury, Pradeep K Singh, Kelly Orcutt, Shil Patel","doi":"10.1007/s11307-026-02113-9","DOIUrl":"https://doi.org/10.1007/s11307-026-02113-9","url":null,"abstract":"<p><strong>Rationale: </strong>Somatostatin receptor subtype 2 (SSTR2) is a G-protein coupled receptor overexpressed in multiple cancers, including neuroendocrine tumors, small cell lung cancer, and hepatocellular carcinoma. Clinical validation of SSTR2-targeted radioligand therapy (Lutathera™) has driven development of next-generation ligands. Progress in next-generation SSTR2 ligand development is strengthened by quantitative platforms that preserve native receptor context and enable quantitative, cross-species binding data to drive translation and radiotherapeutic advancement.</p><p><strong>Methods: </strong>Fresh-frozen tissue sections from mouse, rat, cynomolgus monkey and human brain were assessed for SSTR2 binding using the high affinity antagonist [<sup>177</sup>Lu]Lu-DOTA-LM3. Non-equilibrium kinetics and equilibrium binding methods were used to derive apparent affinity, target density, and affinity measurements. Section-wipe/gamma counting enabled absolute quantification without requiring isotope standards. Autoradiography and SSTR2 immunohistochemistry confirmed anatomic localization. Characterization of unlabeled DOTA-LM3 and its unlabeled lutetium- and gallium-complexed derivatives were compared to assess the effects of radiometal conjugation.</p><p><strong>Results: </strong>Across all species, [<sup>1</sup>⁷⁷Lu]Lu-DOTA-LM3 exhibited specific, saturable binding characteristic of a single class of high-affinity sites. Autoradiography signals co-localized with SSTR2-rich regions identified by immunohistochemistry, confirming expected distribution patterns. Affinities derived from unlabeled and radiolabeled DOTA-LM3 were consistent, validating assay reproducibility. Whilst affinities of agonists and antagonists were conserved across species, radiometal substitution altered ligand properties: the lutetium-complexed form preserved affinity comparable to the chelator-only ligand, while the gallium-complexed variant showed markedly reduced affinity.</p><p><strong>Conclusions: </strong>This native-tissue platform provides efficient, translatable, reproducible and absolute quantification of SSTR2 ligand binding without tissue standards, supporting early selection of chemotypes, radiometals, and species-bridging expectations before in vivo studies.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412345","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}
引用次数: 0
Limited Contribution of T1 Relaxation to GluCEST MRI Signal Differences Across Four Rat Models with Distinct Pathophysiological Features. T1松弛对四种具有不同病理生理特征的大鼠模型中葡萄糖磁共振成像信号差异的有限贡献。
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-07-09 DOI: 10.1007/s11307-026-02119-3
Donghoon Lee, Hind Binjaffar, Yeon Ji Chae, Chul-Woong Woo, Jung-Hyun Choi, Dong-Cheol Woo, Hyunju Ryu, Do-Wan Lee
{"title":"Limited Contribution of T<sub>1</sub> Relaxation to GluCEST MRI Signal Differences Across Four Rat Models with Distinct Pathophysiological Features.","authors":"Donghoon Lee, Hind Binjaffar, Yeon Ji Chae, Chul-Woong Woo, Jung-Hyun Choi, Dong-Cheol Woo, Hyunju Ryu, Do-Wan Lee","doi":"10.1007/s11307-026-02119-3","DOIUrl":"https://doi.org/10.1007/s11307-026-02119-3","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether measured longitudinal relaxation time (T<sub>1</sub>) differences explain glutamate-weighted CEST (GluCEST) group differences across four rat disease models associated with glutamatergic alterations.</p><p><strong>Methods: </strong>GluCEST imaging and quantitative T<sub>1</sub> mapping were performed at 7T in four rat models (insomnia, depression, demyelination, and sepsis). Group differences were assessed using Welch's t-test and standardized effect sizes. The influence of T<sub>1</sub> on GluCEST was examined using disease-specific and pooled analyses of covariance (ANCOVA), as well as correlation analyses.</p><p><strong>Results: </strong>Across all models, T<sub>1</sub> values did not significantly differ between control and disease groups (all p ≥ 0.53), whereas GluCEST showed significant group differences in each condition (all p < 0.01) with large effect sizes (Cohen's d = 1.75-7.02). In ANCOVA models, group effects remained significant after adjustment for T<sub>1</sub>, and T<sub>1</sub> was not a significant predictor of GluCEST in disease-specific or pooled analyses. No consistent correlation between T<sub>1</sub> and GluCEST was observed.</p><p><strong>Conclusions: </strong>Under the present experimental conditions, between-group T<sub>1</sub> differences were limited and did not significantly explain GluCEST group separation across the four rat models examined. These findings suggest that the T<sub>1</sub> contribution to GluCEST group comparisons should be interpreted in relation to the biological model, the magnitude of between-group T<sub>1</sub> differences, and the acquisition conditions.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412196","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}
引用次数: 0
Automated cGMP Radiosynthesis of [18F]NOTA-ABY-030 with Aluminum Fluoride on the GE FASTlab Automated Synthesis Platform. GE FASTlab自动化合成平台上氟化铝自动cGMP辐射合成[18F] nota - abby -030
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-07-09 DOI: 10.1007/s11307-026-02116-6
William Behof, Imtiaz Khan, Julian Grigg, Kamal Jouad, Yiu-Yin Cheung, Fei Liu, Agustina Illan, Eben L Rosenthal, Adam J Rosenberg
{"title":"Automated cGMP Radiosynthesis of [<sup>18</sup>F]NOTA-ABY-030 with Aluminum Fluoride on the GE FASTlab Automated Synthesis Platform.","authors":"William Behof, Imtiaz Khan, Julian Grigg, Kamal Jouad, Yiu-Yin Cheung, Fei Liu, Agustina Illan, Eben L Rosenthal, Adam J Rosenberg","doi":"10.1007/s11307-026-02116-6","DOIUrl":"10.1007/s11307-026-02116-6","url":null,"abstract":"<p><strong>Background: </strong>Epidermal Growth Factor Receptor (EGFR) overexpression in Head and Neck Squamous Cell Carcinoma (HNSCC) is well documented and strongly correlated with aggressive phenotypes. As such EGFR is an excellent choice for molecular imaging of HNSCC as the high overexpression levels allow for a specific marker of tumors. Currently the only established EGFR radiopharmaceuticals that have been translated into human subjects are labeled versions of antibodies and antibody fragments, which all have slow pharmacokinetics and have low specificity due to high background and blood pool. [<sup>18</sup>F]NOTA-ABY-030 is a promising positron emission tomography (PET) radiotracer for in vivo study of the EGFR receptor that alleviates these issues; herein we report the cGMP automated radiosynthesis for use with human subjects.</p><p><strong>Results: </strong>To facilitate clinical trials a fully automated radiosynthesis procedure for [<sup>18</sup>F]NOTA-ABY-030 was developed using commercially available materials on the GE HealthCare FASTlab cassette-based automated radiosynthesis system. The overall synthesis time was 20 min with a radiochemical yield of 47 ± 10% (n = 3). The radiochemical purity was greater than 90% for [<sup>18</sup>F]NOTA-ABY-030 with a binding fraction of 90% (n = 3). The protocol described herein reliably provides [<sup>18</sup>F]NOTA-ABY-030 that meets all relevant release criteria for a GMP radiopharmaceutical.</p><p><strong>Conclusions: </strong>A fast, reliable and efficient automated radiosynthesis was developed using a commercial cassette-based module. This will enable clinical trials work as well as simple method transfer to alternate manufacturing sites; as well as being applicable to small biologic targeting vector radiolabeling.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412442","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}
引用次数: 0
LLM-Enhanced Multimodal Fusion of SPECT Radiomics and Clinical Data for Predicting 131I Therapeutic Response in Differentiated Thyroid Cancer. llm增强SPECT放射组学多模式融合与临床数据预测分化型甲状腺癌131I治疗反应
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-07-08 DOI: 10.1007/s11307-026-02114-8
Hangyu Wang, Erhao Chen, Liqin Pan, Xiaofeng Wu, Songyi Zhang, Li Lin, Ying Sun, Lijun Lu, Wei Ouyang
{"title":"LLM-Enhanced Multimodal Fusion of SPECT Radiomics and Clinical Data for Predicting 131I Therapeutic Response in Differentiated Thyroid Cancer.","authors":"Hangyu Wang, Erhao Chen, Liqin Pan, Xiaofeng Wu, Songyi Zhang, Li Lin, Ying Sun, Lijun Lu, Wei Ouyang","doi":"10.1007/s11307-026-02114-8","DOIUrl":"https://doi.org/10.1007/s11307-026-02114-8","url":null,"abstract":"<p><strong>Background: </strong>Patients with differentiated thyroid cancer (DTC) treated with radioactive iodine (RAI) remain at risk of adverse outcomes. Early prediction of RAI efficacy is critical for optimizing clinical management.</p><p><strong>Purpose: </strong>To develop a model integrating Single Photon Emission Computed Tomography (SPECT) radiomic features and clinical variables for predicting the therapeutic efficacy of 131I treatment in patients with DTC.</p><p><strong>Materials and method: </strong>The SPECT images and clinical data from 311 patients were included in this study. A total of 1,688 radiomic features were extracted from SPECT images. We investigated the diagnostic performance of 30 cross-combined models. Radiomic features were then combined with clinical parameters using early-fusion and late-fusion strategies. To further enhance predictive performance, an input sequence reflecting the selected features and the prediction task was designed and fed into a selected Large Language Model (LLM), which was fine-tuned using low-rank adaptation to optimize fused feature representations. Model performance was evaluated using accuracy (Acc), sensitivity (Sens), positive predictive value (PPV), F1-score, and the area under the curve (AUC).</p><p><strong>Results: </strong>The Relief-F + random forest radiomic model achieved the highest AUC (0.69). Multimodal models combining radiomics with clinical features outperformed clinical-only models, demonstrating the added predictive value of radiomics. The final LLM-enhanced multimodal model achieved the best performance, with an AUC of 0.85 and notable improvements in sensitivity and F1-score.</p><p><strong>Conclusions: </strong>The proposed multimodal framework provides accurate early prediction of RAI therapeutic response in DTC and holds promise for improving individualized treatment planning and follow-up strategies.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412234","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}
引用次数: 0
Direct Androgen Receptor Antagonism Enhances Therapeutic PSMA Radioligand Uptake in Prostate Cancer Models. 直接雄激素受体拮抗剂增强前列腺癌模型治疗性PSMA放射配体摄取。
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-06-21 DOI: 10.1007/s11307-026-02118-4
Philipp E Hartrampf, Sebastian E Serfling, Natalie Hasenauer, Andreas K Buck, Dorothee Rogoll, Charis Kalogirou, Alexander Weich
{"title":"Direct Androgen Receptor Antagonism Enhances Therapeutic PSMA Radioligand Uptake in Prostate Cancer Models.","authors":"Philipp E Hartrampf, Sebastian E Serfling, Natalie Hasenauer, Andreas K Buck, Dorothee Rogoll, Charis Kalogirou, Alexander Weich","doi":"10.1007/s11307-026-02118-4","DOIUrl":"https://doi.org/10.1007/s11307-026-02118-4","url":null,"abstract":"<p><strong>Background: </strong>Prostate-specific membrane antigen (PSMA) is a central target for prostate cancer theranostics. Androgen receptor (AR) signaling has been implicated in regulating PSMA expression; however, whether different modes of AR pathway inhibition uniformly translate into enhanced functional radioligand uptake, particularly for therapeutic applications, remains incompletely defined.</p><p><strong>Methods: </strong>AR-positive (LNCaP, C4-2) and AR-negative (PC3 PSMA +) prostate cancer models were investigated; parental PC3 cells served as PSMA-negative controls. Cells were treated with the direct AR antagonists enzalutamide and apalutamide or with the androgen biosynthesis inhibitor abiraterone. PSMA surface expression was quantified by flow cytometry. Functional uptake of [<sup>18</sup>F]PSMA-1007 and [<sup>177</sup>Lu]Lu-PSMA I&T was assessed by gamma counting. Glucose metabolism was evaluated using [<sup>18</sup>F]FDG uptake, and PSA secretion was measured as a pharmacodynamic readout of AR pathway inhibition.</p><p><strong>Results: </strong>Direct AR antagonism significantly increased PSMA surface expression in AR-positive models and translated into enhanced uptake of the therapeutic radioligand [<sup>177</sup>Lu]Lu-PSMA I&T, with particularly pronounced effects in the castration-resistant C4-2 model. Diagnostic tracer uptake was also increased, though less consistently across models. In contrast, abiraterone did not induce consistent functional enhancement of radioligand accumulation despite PSMA upregulation in selected settings. AR-negative PC3 PSMA + cells exhibited stable baseline PSMA expression but showed no significant changes in PSMA levels or radioligand uptake following AR antagonist treatment. [<sup>18</sup>F]FDG uptake was reduced under AR inhibition in AR-positive models, indicating that enhanced PSMA-targeted uptake was not driven by global metabolic activation.</p><p><strong>Conclusion: </strong>Direct AR antagonism enhances functional PSMA availability and increases short-term uptake of PSMA-targeted radioligands in AR-positive prostate cancer models. These findings provide mechanistic support for AR-mediated modulation of PSMA-targeted radioligand delivery and warrant further translational investigation.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295845","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}
引用次数: 0
Advances in PD-L1 Targeted Molecular Imaging Radiotracers Research: From Preclinical Exploration to Clinical Application. PD-L1靶向分子成像示踪剂的研究进展:从临床前探索到临床应用。
IF 2.5 4区 医学
Molecular Imaging and Biology Pub Date : 2026-06-18 DOI: 10.1007/s11307-026-02115-7
Chang Yu, Ya Liu, Haojie Chen, Ranbie Tang, Huaijia Luo, Xirong Chen, Zhanwen Huang
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