Molecular Imaging and Biology最新文献

{"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 Hasan, Raghavendra Yarlagadda","doi":"10.1007/s11307-026-02090-z","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-04","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":"Engineering Anti-MMP-9 Peptide-Modified Nanoparticles for Precision MRI Diagnosis of Endometriosis.","authors":"Qi Zhang, Haicheng Li, Linghui Xu, Shiman Wu, Yujia Shen, Yiting Wang, Xiongrui Guo, Qianwen Zhu, Xiaohong Ruan, Junhai Zhang","doi":"10.1007/s11307-026-02086-9","DOIUrl":"https://doi.org/10.1007/s11307-026-02086-9","url":null,"abstract":"<p><p>Endometriosis diagnosis is often limited by the resolution of conventional imaging techniques (ultrasound/non-targeted MRI) as well as the invasiveness and recurrence risks associated with laparoscopy. To overcome these challenges, we developed anti-MMP-9 peptide-conjugated NaGdF₄@PEG-Cy5.5 nanoparticles (NPPCNs), which integrate NaGdF₄ cores to enhance T1 relaxivity and biocompatibility for MMP-9-targeted molecular imaging. In vitro studies confirmed both cytocompatibility and high-affinity MMP-9 binding. In vivo biodistribution, assessed through T1-weighted MRI and fluorescence imaging within 48 h post-injection, revealed significant nanoparticle accumulation in endometriotic lesions, with elevated signal intensity compared to controls. This MMP-9-targeted theranostic platform offers a non-invasive method for lesion detection, providing a novel approach for precise diagnosis and surgical navigation in endometriosis.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317708","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":"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":"https://doi.org/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":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging vascular characteristics and glycolytic metabolism of glioblastoma in a chick embryo model using ¹H MRI and [¹⁸F]FDG-PET.","authors":"Elisabeth Non Gash, Jan Schulze, Sarah E Barnett, Mahon L Maguire, Michael Batie, Mohesh Moothanchery, Stephen Pickup, Ian Scott, Rasheed Zakaria, Judy M Coulson, Sonia Rocha, Harish Poptani","doi":"10.1007/s11307-026-02084-x","DOIUrl":"https://doi.org/10.1007/s11307-026-02084-x","url":null,"abstract":"<p><strong>Purpose: </strong>To assess hypoxia-associated host-tumour vascular adaptations and glycolytic metabolism in the chick chorioallantoic membrane (CAM) glioblastoma model.</p><p><strong>Procedures: </strong>U251 GBM cells were conditioned under normoxia (21% O₂) or hypoxia (1% O₂) for 72 h before implantation onto the CAM on embryonic day 7 (E7). Imaging was performed on E13 using MRI (control-CAM n = 8, normoxic-tumour n = 7, hypoxic-tumour n = 6) and brightfield microscopy (control-CAM n = 7, normoxic-tumour n = 8, hypoxic-tumour n = 7). Tumours were harvested on E14 for histology and gene expression analyses. In a separate cohort of 25 GBM-CAM tumours grown under normoxic conditioning, the correlation of glucose metabolism was assessed using [¹⁸F]FDG-PET on E12 followed by lactate MRS on E13 (n = 8).</p><p><strong>Results: </strong>Normoxia- and hypoxia-conditioned tumour-bearing CAMs exhibited vascular remodelling and significant upregulation of VEGFA and ADM compared to cultured cells. αSMA staining confirmed vessel infiltration in normoxia-conditioned tumours. CAIX staining revealed a hypoxic core in these tumours while hypoxia-conditioned tumours displayed heterogeneous staining. In both conditions, GLUT1 staining colocalised with CAIX staining, indicating hypoxia-associated glycolysis. GLUT1, PDK1 and LDHA expression was elevated in CAM tumours relative to tumour cells in vitro. In the metabolic imaging cohort, most tumours exhibited [¹⁸F]FDG uptake and lactate signal. However, no statistically significant relationship was observed between the two methods.</p><p><strong>Conclusions: </strong>The CAM model provides a versatile platform for investigating GBM vascularisation and metabolism. Hypoxic conditioning amplifies transcriptional and vascular changes to the CAM. Although both [¹⁸F]FDG uptake and lactate were measurable, no significant correlation between the two was observed, potentially reflecting variability in tumour engraftment, vascular delivery of [¹⁸F]FDG, and microenvironmental influences on lactate accumulation.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276646","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":"https://doi.org/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":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theranostic and Radionuclide-based Treatment Approaches for Radioiodine-refractory Thyroid Cancer: From Biology to Clinical Application.","authors":"Mubeen Hussein Arawker, Fitrat Habibullah, Lijun Fu, Shantanu Baral, Xinguang Qiu","doi":"10.1007/s11307-026-02082-z","DOIUrl":"https://doi.org/10.1007/s11307-026-02082-z","url":null,"abstract":"<p><p>When differentiated thyroid cancer stops taking up radioiodine, treatment becomes significantly more challenging, and the disease often behaves more aggressively. Systemic therapies such as multikinase inhibitors and mutation-specific drugs have expanded available options, but many patients experience side effects, and responses can vary widely. At the same time, advances in molecular imaging and targeted radionuclide therapy are changing how this condition is managed. Short-term MAPK inhibition can restore iodine uptake in some patients, creating an opportunity to give radioiodine again. For patients with spreading or fast-growing disease, a growing range of theranostic agents, including ¹⁷⁷Lu and ²²⁵Ac-based treatments directed at SSTR, PSMA, or FAP, provides a more targeted approach that is guided by PET imaging and has shown promising activity in early clinical experience- The increasing use of quantitative PET information, radiomic analysis, and personalized dosimetry may further support better treatment selection. Despite these developments, the optimal combination of radionuclide therapy with redifferentiation strategies, multikinase inhibitors, and gene-targeted treatments remains unclear. This review brings together current and emerging treatment approaches for radioiodine-refractory thyroid cancer and discusses how theranostics may become part of routine care.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220160","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":"Exploration of the Feasibility of One-Day Dual-Low-Activity ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/MR in Patients with Neuroendocrine Neoplasms.","authors":"Wenjin Zhao, Lifang Pang, Yunze Xie, Wenxin Tang, Hongcheng Shi","doi":"10.1007/s11307-026-02081-0","DOIUrl":"https://doi.org/10.1007/s11307-026-02081-0","url":null,"abstract":"<p><strong>Purpose: </strong>The standard 2-day dual-tracer PET protocol provides more information but is time consuming. Thus, this study aimed to validate the feasibility of 1-day ⁶⁸Ga-DOTATATE and ¹⁸F-FDG dual-low-activity PET/MR imaging in patient with neuroendocrine neoplasms (NENs).</p><p><strong>Procedures: </strong>Fourteen NENs patients who underwent 1-day ⁶⁸Ga-DOTATATE and ¹⁸F-FDG dual-low-activity PET/MR, and another 14 patients matched with the same primary tumor sites and tumor grades who underwent 2-day ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/MR were retrospectively enrolled. Imaging analysis was performed, including lesion detection rate and diagnostic confidence. Additionally, the diagnostic confidence was also assessed based on ⁶⁸Ga-DOTATATE PET, ¹⁸F-FDG PET and PET/MR, respectively.</p><p><strong>Results: </strong>The 1-day protocol detected 39 out of 40 lesions in 14 patients, while the 2-day protocol detected 65 out of 66 lesions in 14 patients. No significant differences were observed in lesion detection (all P > 0.05). There was no significant difference in diagnostic confidence between the 1-day protocol and the 2-day protocol for ⁶⁸Ga-DOTATATE PET (median [IQR]: 3[2-3] vs. 3[2-3]), ¹⁸F-FDG PET (1[1-2] vs. 1[1-1]), and PET/MR (4[3-5] vs. 5[4-5]) in all lesions (all P > 0.05).</p><p><strong>Conclusion: </strong>The 1-day ⁶⁸Ga-DOTATATE and ¹⁸F-FDG dual-low-activity PET/MR imaging protocol in patients with NENs is feasible and provides equivalent lesion detection and diagnostic confidence compared to the 2-day protocol.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181186","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":"Enhanced Fluorescence of Near-Infrared Anti-CEA Antibodies for Visualizing Colorectal Cancers Using Modified Heptamethine Cyanines.","authors":"K Cox, J Jitender, S Mehta, Dong-Hao Li, S Amirfakhri, R M Hoffman, J Shively, P Yazaki, M J Schnermann, M Bouvet, T M Lwin","doi":"10.1007/s11307-025-02076-3","DOIUrl":"https://doi.org/10.1007/s11307-025-02076-3","url":null,"abstract":"<p><strong>Background: </strong>The clinical success of fluorescence-guided surgery is dependent on tumor-specific probes that can achieve high tumor-to-background contrast. Conventional near-infrared (NIR) fluorophores often alter the pharmacokinetic properties of the parental molecule that result in aggregation, altered biodistribution, and impaired tumor targeting.</p><p><strong>Methods: </strong>This present study evaluates two charge-balanced heptamethine cyanine dyes, FNIR-Tag-766 and FNIR-Tag-804, conjugated to a humanized anti-carcinoembryonic antigen antibody (M5A). Their performance was compared to the standard M5A-IR800CW conjugate in both subcutaneous and orthotopic colorectal cancer xenograft models in mice. Mean fluorescence intensity (MFI), tumor-to-background ratio (TBR), and ex vivo biodistribution were compared.</p><p><strong>Results: </strong>The M5A-FNIR-766 conjugate produced a greater MFI in tumors at all timepoints compared to M5A-IR800CW, resulting in a significantly improved TBR. Ex vivo analysis at 96 h confirmed higher tumor accumulation for M5A-FNIR-766 and revealed a reduction in hepatic signal for both M5A-FNIR-Tag conjugates. The observations were concordant in the clinically relevant orthotopic model.</p><p><strong>Conclusion: </strong>Antibody-fluorophore conjugates linked to the charge-modified FNIR-Tag dyes provide improved tumor-specific signals and a more favorable biodistribution profile than the same antibody conjugated to a conventional dye. By achieving superior performance through intrinsic fluorophore design rather than complex bioconjugation strategies, the approach provides a clinically translatable advancement for tumor-specific FGS.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157567","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 Macrophages in Cardiovascular Diseases.","authors":"Jia Xu, Wei Sun, Xin Zhang, Yinting Xiong, Jiani Qiu, Tang Gao, Haiyan Cao, Li Zhang, Mingxing Xie, Qing Lv, Wenqian Wu","doi":"10.1007/s11307-026-02080-1","DOIUrl":"https://doi.org/10.1007/s11307-026-02080-1","url":null,"abstract":"<p><p>Molecular imaging exhibits remarkable potential in immune cell tracking and advancing personalized clinical management, providing not only diagnostic and prognostic information but also enabling treatment efficacy quantification and therapeutic optimization. Macrophages play an essential role in the pathogenesis and progression of various cardiovascular diseases. This review comprehensively examines the characteristics of diverse molecular imaging modalities and their applications in macrophage imaging, encompassing major cardiovascular conditions, including atherosclerosis, myocardial infarction, and cardiac transplantation. We anticipate that advancements in novel noninvasive molecular imaging technologies for macrophages will ultimately facilitate clinical diagnosis, outcome prediction, treatment strategy formulation, and therapy response monitoring, thereby providing critical technical support for precision medicine practice.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132325","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}