Molecular Imaging and Biology最新文献

{"title":"Value of Multitracer Imaging in Hepatocellular Carcinomas with Different Metastatic Potential.","authors":"Tingting He, Cong Zhang, Jinming Zhang, Xiaojun Zhang, Ruimin Wang","doi":"10.1007/s11307-026-02088-7","DOIUrl":"10.1007/s11307-026-02088-7","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) shows marked heterogeneity and varying metastatic potential, challenging prognosis and treatment. This study evaluated multitracer PET imaging with [¹⁸F]FDG, [¹⁸F]FLT, and [¹⁸F]ACE to differentiate HCCs by metastatic behavior and explored its prognostic relevance.</p><p><strong>Methods: </strong>Four human HCC cell lines with varying metastatic potential (HepG2, QGY7701, MHCC97-H, MHCC97-L) were assessed for in vitro tracer uptake, proliferation, and invasion. Subcutaneous and spontaneous metastasis models were established in nude mice. Tumor uptake of tracers was quantified via microPET/CT. mRNA expression of MMP9 and VEGFR-2 and survival were analyzed. Fisher's classifier was applied to compare single-, dual-, and triple-tracer datasets with cross-validation.</p><p><strong>Results: </strong>Tracer uptake significantly differed among cell lines (p < 0.001). The triple-tracer model ([¹⁸F]FDG + [ ¹⁸F]FLT + [¹⁸F]ACE) yielded the lowest classification error rate (0.074) compared with dual tracers (0.085-0.362). In vivo, [¹⁸F]FDG uptake correlated with metastatic potential, MMP9 and VEGFR-2 expression (r = 0.770-0.830, p < 0.05), and inversely with survival (r = - 0.726, p = 0.005). There is a significant difference in FDG uptake values between high-metastatic and low-metastatic cell lines as well as in tumor model.[¹⁸F]FLT uptake showed moderate correlation with biomarkers but not with survival, while [¹⁸F]ACE had no significant discriminative value.</p><p><strong>Conclusions: </strong>A multiparameter (multitracer) classification model had superior ability to discriminate four HCC cell lines with different biological behavior compared with dual tracers or single tracer through in vitro cell uptake experiment. [1⁸F]FDG uptake can distinguish between tumor models with high and low metastatic potential, and [1⁸F]FDG uptake can predict the survival time in metastatic models. [¹⁸F]FDG uptake probably be noninvasive prognostic marker, reflecting tumor heterogeneity and correlating with survival and metastasis-related biomarkers. This approach may aid in clinical stratification and personalized management of HCC.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"309-319"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284599","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":"Malignant Pleural Mesothelioma (MPM) Evaluation with [¹¹C]-Methionine PET/CT Before and After Talc Pleurodesis.","authors":"Egesta Lopci, Angelo Castello, Alberto Testori, Emanuele Voulaz, Daoud Rahal, Matteo Perrino, Alessandro Crepaldi, Giorgio Maria Ferraroli, Valentina Errico, Edoardo Bottoni, Marcello Rodari, Lorenzo Muraglia, Giuseppe Marulli, Marco Alloisio, Paolo Andrea Zucali","doi":"10.1007/s11307-026-02093-w","DOIUrl":"10.1007/s11307-026-02093-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Malignant pleural mesothelioma (MPM) poses an imaging challenge that requires special attention, especially in patients who have undergone talc pleurodesis. [&lt;sup&gt;18&lt;/sup&gt;F]FDG PET/CT (FDG PET) is a validated imaging modality in oncology that has proven useful for detecting malignant pleural lesions. However, the inflammatory reaction induced by pleurodesis renders its interpretation unreliable. In this study, we assessed in parallel the role of [&lt;sup&gt;11&lt;/sup&gt;C]Methionine PET/CT (MET PET) and FDG PET in MPM patients before and after talc pleurodesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;We prospectively enrolled 30 consecutive patients with clinical suspicion of MPM who were referred to our Institution from September 2014 to February 2016 for talc pleurodesis. The study was approved and registered at ClinicalTrials.gov (NCT02519049). Patients underwent assessment at baseline and after pleurodesis with two consecutive scans: FDG PET (standard imaging) and MET PET (experimental imaging). Semi-quantitative parameters were defined for both scans and statistically compared to pathological findings from video-assisted thoracoscopy (VATS), including SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis for FDG PET or metabolic tumor burden (TLG or MTB = MTV x SUVmean) for MET PET.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty patients (M:F = 18:2; median age, 72 years) with MPM (18 epithelioid, 2 non-epithelioid) completed all study investigations. All tumors showed increased uptake of both FDG and MET PET. After talc pleurodesis, FDG PET showed a significant increase in mean and median MTV (P = 0.0005 and 0.0003, respectively) and mean and median TLG (P = 0.0172 and 0.0028, respectively). In contrast, MET PET parameters showed significant increases in mean and median SUVmax (P = 0.0208 and 0.0209, respectively) and SUVmean (P = 0.0106 and 0.0109, respectively) compared to baseline. There was a significant negative correlation between SUVmax, MTV and MTB/TLG and the percentage change at the early assessment post-pleurodesis for both MET PET (rho = -0.645, P &lt; 0.01; rho = -0.517, P = 0.013; rho = -0.528, P = 0.011, respectively) and FDG PET (rho = -0.808, P &lt; 0.01; rho = -0.781, P &lt; 0.01; rho = -0.888, P &lt; 0.01, respectively). The percentage change in SUVmax was significantly greater in FDG PET than for MET PET (+ 19% vs + 16%, P = 0.03). Additionally, mean and median MTV were significantly higher on FDG PET than MET PET (mean + 1022.3 vs + 224.2, P = 0.01; median + 157.5 vs + 7.1, P = 0.02).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study confirms the impact of talc pleurodesis on FDG PET, particularly for volumetric parameters (MTV and TLG). MET PET appears less influenced by post-pleurodesis inflammatory reaction than FDG PET, with changes mostly limited to SUVmax and SUVmean. Clinical Trial Number (NCT02519049) at the Clinical Trial Registry ( https://www.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinicaltrials: &lt;/strong&gt;gov","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"280-289"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390526","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":"Photoacoustic Imaging of Muscle Tissue Oxygenation as a Noninvasive Biomarker in Mouse Models of Sickle Cell Disease.","authors":"Jeffrey Morin, Megan Brophy, John Stansfield, Debra Pittman, Dinesh Hirenallur-Shanthappa","doi":"10.1007/s11307-026-02095-8","DOIUrl":"10.1007/s11307-026-02095-8","url":null,"abstract":"<p><strong>Purpose: </strong>To develop and validate photoacoustic imaging (PAI) as a method to assess hemoglobin counts and muscle tissue oxygen saturation in a mouse model of Sickle Cell Disease (SCD.</p><p><strong>Procedures: </strong>In vivo PAI was performed on mice with a SCD phenotype and results were compared to those from animals carrying a homozygous knockout of Bisphosphoglycerate mutase (BPGM), meant to annul the SCD phenotype, as well as controls (129 strain), then further compared to sickling assay results of blood collected from the same mice.</p><p><strong>Results: </strong>PAI of the hindlimb muscles of SCD mice demonstrated significant decrease in tissue oxygen saturation (sO2) compared to control mice (28.4% vs 35.5%). Further PAI of mice with a genetic knock out of BPGM on an SCD background revealed tissue sO2 significantly greater (32.6%) than SCD mice and close to those in controls. These results correlate well with standard measurements of RBC sickling via cell counts. Hemoglobin counts derived from PAI further confirm the reduced tissue oxygen saturation measurements in SCD mice.</p><p><strong>Conclusions: </strong>PAI synergizes the specificity of optical imaging with the depth penetration capability of ultrasound to measure tissue oxygen saturation at deeper levels of tissue. The results of this study suggest this imaging method can be used to non-invasively measure hemoglobin counts and tissue oxygen levels as in vivo biomarkers in preclinical models of SCD, and potentially in the clinic as well.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"382-391"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434298","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":"Template-Directed RIG-I Agonist Assembly for Image-guided Targeted Cancer Immunotherapy.","authors":"Subrata K Ghosh, Douglas Lazarus, Neil Robertson, Qiyong P Liu, Elizabeth Kenyon, Christian L Mallett, Ming Chen, Zdravka Medarova, Anna Moore","doi":"10.1007/s11307-026-02087-8","DOIUrl":"10.1007/s11307-026-02087-8","url":null,"abstract":"<p><strong>Purpose: </strong>Tumor-specific immunotherapies selectively target tumor cells with reduced toxicity compared to conventional treatments. Pattern recognition receptors, such as retinoic acid-inducible gene I (RIG-I)-like receptors, have been used to induce broad antitumor responses but their off-target effects and delivery issues hinder their clinical translation. To overcome these challenges, we present a strategy that involves the intracellular assembly of the RIG-I agonist on a tumor-specific RNA template (e.g., miRNA-21) by delivering a 5'-triphosphate single-stranded RNA RIG-I agonist (RIGA-miRNA-21) by a superparamagnetic nanoparticle carrier (TTX) to initiate specific RIG-I signaling and antitumor immune responses. Magnetic properties of TTX enable its detection by magnetic resonance imaging (MRI) supporting the concept of image-guided therapy.</p><p><strong>Procedures: </strong>A single-stranded anti-miR-21 5'-triphosphate RIG-I agonist was conjugated to the dextran coat of the nanoparticles through disulfide bonds producing TTX-RIGA-miR-21 and tested in vitro and in vivo in B16-F10 melanoma model. Delivery of the TTX carrier was demonstrated in mice bearing B16-F10 tumors by MRI. Therapeutic studies included intravenous injections of TTX-RIGA-miR-21 or controls for 7 days starting on Day 4 after tumor implantation. On Day 15, animals were rechallenged with additional B16-F10 cells implanted on the opposite side.</p><p><strong>Results: </strong>We demonstrated that TTX-RIGA-miR21 was able to induce miRNA-21-dependent RIG-I signaling and apoptosis in melanoma cells, inhibit tumor growth, and induce immunity against tumor rechallenge in an animal model.</p><p><strong>Conclusions: </strong>Our template-driven approach brings RIG-I closer to becoming a clinically relevant target in oncology by specifically activating immune responses within tumor cells through systemic RIG-I agonist delivery.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"320-333"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146227284","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":"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/s11307-026-02090-z","DOIUrl":"10.1007/s11307-026-02090-z","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) remains a major clinical challenge owing to its inherent resistance to treatment, immune-competent tumor microenvironment, and early metastasis. Sonodynamic therapy (SDT), which generates reactive oxygen species (ROS) using ultrasound, is a promising approach that combines localized apoptosis with systemic immune activation. In this review, we integrate biophysical principles, immunological targets, and nanoplatform design into diamond structures (discover, define, development, and deliver). We discuss the physical basis of SDT, including acoustic cavitation, sonoluminescence, and piezocatalysis; the non-apoptotic modalities of ferroptosis, pyroptosis, and mitophagy; and the activation of innate nucleic acid receptor-sensing pathways, such as the cGAS-STING. We are exploring nanotechnology, including oxygen-generating catalysts, GSH-depleting constructs, biomimetic and stimulus-responsive carriers for hypoxia and redox suppression, and theranostic probes. We assessed the durability of anti-tumor immunity induced by combination therapies. Finally, we outline the necessary preclinical toxicology and pharmacodynamics based on biomarkers to implement SDT as a programmable immuno-nanomedicine for aggressive TNBC.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"238-259"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355844","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 Biodistribution and Dosimetry of [¹¹C]Trimethoprim.","authors":"Anthony J Young, Robert K Doot, Joshua K Cho, Jonathan M Pham, Alvaro A Ordonez, Andres F Del Castillo, Tiffany L Dominguez, Supritha Dugyala, Erin K Schubert, Hsiaoju Lee, Austin R Pantel, Robert H Mach, David A Mankoff, Mark A Sellmyer","doi":"10.1007/s11307-025-02064-7","DOIUrl":"10.1007/s11307-025-02064-7","url":null,"abstract":"<p><p>Trimethoprim (TMP) is a reversible inhibitor of the prokaryotic enzyme dihydrofolate reductase (DHFR) used for the treatment or prophylaxis of bacterial infections. [¹¹C]trimethoprim ([¹¹C]TMP) is a positron emission tomography (PET) imaging isotopologue of TMP. TMP binds with 30,000-fold greater affinity to bacterial DHFR over the homologous mammalian enzyme in vitro, suggesting [¹¹C]TMP may selectively accumulate in tissues with cells expressing bacterial DHFR. This study characterizes the biodistribution and dosimetry of [¹¹C]TMP, informing its use in imaging bacterial infections and tracking mammalian cells expressing eDHFR as a reporter gene.</p><p><strong>Methods: </strong>Four males with suspected infection, aged 59 ± 10 years old (mean ± SD) received 3 serial PET/CT scans after injection of 346 ± 305 MBq (range 129-797 MBq) of [¹¹C]TMP. Organ activities were measured in MIM v6.7, including brain, kidneys, spleen, liver, heart, lungs, bladder, intestines, gallbladder, pancreas, thyroid, and red marrow. Dosimetry calculations were performed in Olinda | EXM v1.1. Additionally, a dynamic whole-body PET/CT scan was performed on a separate participant. The associated trial was registered as NCT03424525.</p><p><strong>Results: </strong>[¹¹C]TMP injections were well tolerated with no adverse events. The average injected activity of 346 MBq of [¹¹C]TMP yielded an estimated average dose of 4.9 mSv in the highest uptake organ (liver), 4.1 mSv in the spleen, and an effective dose of 1.6 mSv. Suspected sites of infection displayed uptake above background.</p><p><strong>Conclusion: </strong>[¹¹C]TMP PET was safe and demonstrated low background uptake in most tissues. The data suggests feasibility for evaluation of varied bacterial infections, including musculoskeletal infections. Absorbed doses allow multiple [¹¹C]TMP PET scans each year within Radioactive Drug Research Committee (RDRC) limits, potentially enabling monitoring of infections and treatment response.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"60-67"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12966202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582115","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":"Staging Prostate Cancer with AI: A Comparative Study of Large Language Models and Expert Interpretation on PSMA PET-CT Reports.","authors":"Rashad Ismayilov, Ayse Aktas, Esra Arzu Gencoglu, Arzu Oguz, Ozden Altundag, Zafer Akcali","doi":"10.1007/s11307-025-02072-7","DOIUrl":"10.1007/s11307-025-02072-7","url":null,"abstract":"<p><strong>Purpose: </strong>Accurate staging of prostate cancer is essential for therapeutic decision-making. While PSMA PET-CT reports offer rich clinical data, their unstructured format hinders large-scale analysis. Recent advances in large language models (LLMs) offer new opportunities to extract structured information from narrative radiology reports. However, their ability to perform multi-step clinical reasoning, particularly for cancer staging, remains underexplored.</p><p><strong>Methods: </strong>In this feasibility study, 80 anonymized, Turkish-language PSMA PET-CT reports were independently interpreted by two LLMs-Gemini 2.5 Pro (Google) and ChatGPT 4o (OpenAI). Using a structured prompt containing an embedded knowledge base (AJCC/CHAARTED criteria) and few-shot examples, both LLMs generated classifications for T, N, M, and overall clinical stage/disease volume. Outputs were benchmarked against expert classifications by a senior nuclear medicine specialist. Performance was evaluated using accuracy, precision, recall, F1-score, and Cohen's kappa.</p><p><strong>Results: </strong>For the composite task of classifying clinical stage and disease volume, Gemini 2.5 Pro achieved an accuracy of 93.8% (95% CI: 86.0-97.9) and a Cohen's kappa of 0.910 (95% CI: 0.834-0.986), while ChatGPT 4o achieved 91.3% accuracy (95% CI: 82.8-96.4) with a kappa of 0.874 (95% CI: 0.786-0.962). For T staging, Gemini showed a higher accuracy point estimate (95.0% [95% CI: 87.7-98.6] vs. 91.3% [95% CI: 82.8-96.4]), while both models excelled at the binary N and M classifications, achieving accuracies above 95% and kappa values indicating near-perfect agreement (κ > 0.900).</p><p><strong>Conclusions: </strong>LLMs, when guided by expert-informed prompt engineering, can accurately stage prostate cancer from free-text PSMA PET-CT reports and may serve as a powerful assistive tool for data automation, research acceleration, and quality assurance.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"93-105"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687568","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":"¹²⁴I-Labeled Specific Antibody Targeting LAG-3 for ImmunoPET.","authors":"Lixin Ding, Feng Wang, Yongxiang Pan, Wenting Liu, Liansheng Cheng, Fei Tuo, Kuke Ding, Hua Zhu, Zhi Yang","doi":"10.1007/s11307-025-02079-0","DOIUrl":"10.1007/s11307-025-02079-0","url":null,"abstract":"<p><strong>Purpose: </strong>Lymphocyte-activation gene 3 (LAG-3), a next-generation immune checkpoint, has emerged as a promising therapeutic target, but noninvasive tools for evaluating LAG-3 expression remain limited. Herein, we explored an antibody-dependent molecular imaging strategy for noninvasive detection based on a LAG-3-specific antibody, HuL13.</p><p><strong>Procedures: </strong>The anti-LAG-3 antibody HuL13 was radiolabeled with ¹²⁴I via electrophilic substitution. LAG-3-expressing A549 cells were constructed by infection with the lentivirus. The specificity and affinity of ¹²⁴I-HuL13 to LAG-3 receptor were evaluated by cell uptake assay and saturation binding assay. Micro-PET/CT imaging studies were conducted in BALB/c nude mice bearing LAG-3⁺ A549 tumors. Immunohistochemistry (IHC) validated LAG-3 expression in tumors.</p><p><strong>Results: </strong>The ¹²⁴I-HuL13 exhibited a good radiochemical yield of 95.59 ± 1.27%, high radiochemical purity (RCP, > 99%), and excellent stability. Cell binding assays demonstrated that ¹²⁴I-HuL13 had a higher binding ability to LAG-3⁺ A549 cells compared to control cells. The equilibrium dissociation constant (Kd) of ¹²⁴I-HuL13 was 23.02 nM for LAG-3⁺ A549 cells. In vivo pharmacokinetics revealed favorable metabolic stability (t_1/2β = 12.07 h). Micro-PET/CT images showed that ¹²⁴I-HuL13 significantly accumulated in LAG-3⁺ A549 tumor from 24 h after injection (SUVmax = 0.34 ± 0.03 at 24 h), and high contrast tumor to background imaging was clearly observed. IHC confirmed LAG-3 expression correlated with probe uptake.</p><p><strong>Conclusions: </strong>¹²⁴I-HuL13 is a novel LAG-3-targeted PET imaging radiotracer with excellent stability. This study highlights ¹²⁴I-HuL13 as a robust tool for noninvasive LAG-3 imaging, offering potential for optimizing LAG-3-targeted immunotherapy in clinical settings.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"68-80"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810649","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":"Molecular Imaging of Pancreatic Duct Adenocarcinoma Using [¹⁸F]JR-1004, a Cannabinoid Type 2 Receptor Targeted Positron Emission Tomography (PET) Probe.","authors":"Can Jin, Xinghai Cao, Junwei Chen, Dilong Mao, Qinggang He","doi":"10.1007/s11307-025-02069-2","DOIUrl":"10.1007/s11307-025-02069-2","url":null,"abstract":"<p><strong>Purpose: </strong>Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a 5-year survival rate below 10% and poor prognosis. Early diagnosis of PDAC remains a significant challenge due to its nonspecific symptomatology, insufficient reliable biomarkers, aggressive tumor progression with early metastatic spread, and limited effective screening protocols. Recent research indicates cannabinoid type 2 receptor (CB2R) overexpression in PDAC, leading to the development of [¹⁸F]JR-1004 as a potential CB2R-targeted PET probe to address diagnostic challenges in this aggressive malignancy.</p><p><strong>Procedures: </strong>The probe development utilized computer-aided drug design, incorporating modifications to a triaryl sulfonamide CB2R inverse agonist lead compound. Essential pharmacophoric elements (central sulfonamide, flanking aromatic rings) were preserved, while the para-methoxy group underwent conversion to a tosylate precursor for radiolabeling. Radiolabeling with ¹⁸F was performed using a JiRui OnePlatform 3.1 s synthesizer (synthesis time: 70 min).</p><p><strong>Results: </strong>The radiochemical purity and yield achieved values exceeding 95% and 16.7%, respectively. In vitro studies confirmed [¹⁸F]JR-1004's specific binding affinity in CB2R-overexpressing cells, with uptake significantly reduced by a CB2R antagonist administration. PET imaging in PDAC mouse models revealed significant accumulation in tumor regions, with receptor specificity validated through CB2R blocking studies. Biodistribution analysis revealed primary probe metabolism through the hepatobiliary system, with maximal uptake in the liver and pancreas. The probe's targeting profile demonstrates notable improvements for PDAC detection compared to the relatively nonspecific uptake patterns of [¹⁸F]FDG PET in pancreatic imaging.</p><p><strong>Conclusions: </strong>This investigation presents an innovative molecular imaging approach for early PDAC diagnosis, exhibiting considerable potential for clinical implementation.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"23-36"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687321","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":"PET Imaging of CD38 and IND enabling studies of [⁸⁹Zr]Zr-DFO-Isatuximab.","authors":"Brian D Wright, Hailey A Houson, Solana Fernandez, Kadir Gultekin, Jonathan E McConathy, Smith Giri, Suzanne E Lapi","doi":"10.1007/s11307-025-02062-9","DOIUrl":"10.1007/s11307-025-02062-9","url":null,"abstract":"<p><strong>Background: </strong>CD38 is an excellent biomarker and therapeutic target for multiple myeloma due to its high expression on cancerous cells in comparison to healthy cells.</p><p><strong>Purpose: </strong>We aimed to adapt Isatuximab as a PET imaging agent to detect CD38 positive multiple myeloma.</p><p><strong>Methods: </strong>In vitro studies confirmed the specificity of [⁸⁹Zr]Zr-DFO-Isatuximab in CD38 + OPM-2 and MM.1S cells. Upregulation of CD38 was performed using pomalidomide and ricolinostat. Athymic nude mice were implanted with OPM-2 tumors and PET/CT images were collected 24 h, 3d, and 7d post-injection. Dosimetry data was collected from male and female mice and calculated using OLINDA. Three productions of [⁸⁹Zr]Zr-DFO-Isatuximab were produced using GMP techniques and validated for use in the clinic.</p><p><strong>Results: </strong>Upregulation of CD38 was observed in vitro in CD38 + cells when treated with either pomalidomide or ricolinostat. In vivo evaluation of [⁸⁹Zr]Zr-DFO-Isatuximab showed high selectivity in OPM-2 xenografts. Blocking with an excess of unlabeled Isatuximab reduced the tumor accumulation of [⁸⁹Zr]Zr-DFO-Isatuximab by 45.5-48.5% confirming the in vivo specificity of this radiotracer. Dosimetry calculations were performed and showed an estimated effective dose of 0.359 mSv/MBq in females and 0.327 mSv/MBq in males. Three clinical grade [⁸⁹Zr]Zr-DFO-Isatuximab doses using good manufacturing practices were synthesized which passed all quality control requirements and were stable up to 6 h, thus validating this compound for use in future clinical trials.</p><p><strong>Conclusion: </strong>[⁸⁹Zr]Zr-DFO-Isatuximab showed high specificity to CD38 positive cells, had estimated effective doses comparable to other clinically relevant ⁸⁹Zr-labeled antibodies, and can be prepared using GMP practices for clinical use.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"49-59"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12966236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708797","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}