Molecular Imaging And Biology[JOURNAL]
Sun
200 papers
Preclinical Study of Radiolabeled LyP-1 for Detecting Sunitinib-induced Changes in the Tumor Microenvironment and Synergistic Antitumor Effects in Triple-negative Breast Cancer.
Liao S, Qi Q, Jin L … +5 more , Gong J, Zhao L, Zhao J, Zhu M, Song N
Mol Imaging Biol · 2026 Apr · PMID 41922884 · Publisher ↗
PURPOSE: Sunitinib is an anti-angiogenic drug that can induce drug resistance characterized by hypoxia. We aimed to synthesize two novel radiolabeled LyP-1 peptides, Tc-HYNIC-LyP-1 and I-LyP-1, to detect sunitinib-induce...
PURPOSE: Sunitinib is an anti-angiogenic drug that can induce drug resistance characterized by hypoxia. We aimed to synthesize two novel radiolabeled LyP-1 peptides, Tc-HYNIC-LyP-1 and I-LyP-1, to detect sunitinib-induced changes in the tumor microenvironment and improve the therapeutic effects in triple-negative breast cancer (TNBC) mice models. METHODS: We synthesized Tc-HYNIC-LyP-1 using hydrazinonicotinamide (HYNIC) as the chelating agent and labeled the LyP-1 peptide with I using the chloramine-T method to synthesize I-LyP-1. Radiochemical purity and stability of the peptides were assessed in vitro using thin-layer chromatography. Tumor accumulation and biodistribution of Tc-HYNIC-LyP-1 were measured in 4T1 xenografts with or without sunitinib treatment. Immunohistochemical analysis was performed to detect sunitinib-induced changes. The therapeutic potential of I-LyP-1 alone and in combination with sunitinib was evaluated in a TNBC mouse model. RESULTS: Tc-HYNIC-LyP-1 and I-LyP-1 could be readily prepared with satisfactory labeling efficiency (95.4% ± 0.6% and 72.5% ± 4.5%, respectively) and stability (both more than 90%) in vitro. Micro-single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of mice transplanted with 4T1 tumors using Tc-HYNIC-LyP-1 demonstrated that the uptake of this probe was high in 4T1 xenografts treated with sunitinib at 90 min, whereas it was mild in the control group. Semiquantitative analysis of the ratio of radioactivity intensity at tumor site to that of adjacent muscles (T/M value) showed that the average T/M value of the sunitinib treatment group at 90 min was 3.27, while it was 0.91 in the control group (p = 0.0022). I-LyP-1 could significantly inhibited tumor growth with good organ compatibility and had a synergistic therapeutic effect when combined with sunitinib, with an approximately threefold reduction in the tumor volume in comparison with the control group CONCLUSION: Micro-SPECT/CT imaging using Tc-HYNIC-LyP-1 can be used to monitor sunitinib-induced changes in the TNBC tumor microenvironment. The combination of I-LyP-1 and sunitinib may serve as a novel treatment for TNBC.
Astrocyte Activation Persists after Recovery of Myelin and Motor Deficits in the Cuprizone Model: a Longitudinal PET and CNS Tissue Analysis Study.
Pegoretti V, Boerema AS, Sijbesma JWA … +5 more , Dietz LER, Alberts N, Douwenga W, Eisel ULM, de Vries EFJ
Mol Imaging Biol · 2026 Mar · PMID 41874822 · Publisher ↗
PURPOSE: The cuprizone (CPZ) mouse model for multiple sclerosis enables researchers to investigate the underlying mechanisms of demyelination and remyelination, as well as the effect of therapeutic interventions thereon....
PURPOSE: The cuprizone (CPZ) mouse model for multiple sclerosis enables researchers to investigate the underlying mechanisms of demyelination and remyelination, as well as the effect of therapeutic interventions thereon. Over the last five decades, research revealed detailed analyses of brain tissue derived from CPZ-fed animals at different times of de- and re-myelination. Yet, longitudinal analysis of the effects of a CPZ diet on locomotor performance, myelination and neuroinflammation over a two-month recovery period are still unexplored. PROCEDURES: In this study, we comprehensively examined behavioural and neuropathological changes in the CPZ mouse model for a follow-up period of two months. We combined a longitudinal PET imaging approach with a more traditional approach of obtaining tissue and performing immunohistochemistry and behavioural tests in cohorts. RESULTS: We found that mice fed with 0.2% CPZ for 5 weeks showed transient motor deficits which recovered quickly after cuprizone was removed from the diet. Similarly, remyelination also promptly restored myelin content after CPZ toxic insult, as seen by PET imaging with [C]MeDAS and myelin histological staining. Remarkably, five weeks of CPZ feeding led to persistent glial activation, especially in the corpus callosum, for at least two months. This effect was measured both with [C]PK11195 PET and with immunohistochemical staining for microglia and astrocytes. CONCLUSIONS: Taken together, this longitudinal study reveals that a five-week CPZ diet leads to transient motor and loss of myelin, which recover quickly after CPZ is removed. In contrast, neuroinflammation persists for at least two months following exposure and is mainly driven by astrocyte activation. The study warrants deeper analysis of the sustained neuroinflammatory response in the context of demyelinating diseases.
Comparison of [F]FDG and [F]PSMA-1007 PET/CT in the Evaluation of Muscle-Invasive Bladder Cancer: A Pilot Feasibility Study.
Avilez ND, Tineo RN, Rodrigues JT … +6 more , Ottaiano AD, Saito HPA, Amorim BJ, Carvalheira JBC, Reis LO, Ramos CD
Mol Imaging Biol · 2026 Apr · PMID 41872599 · Full text
PURPOSE: To compare the diagnostic performance of [F]FDG and [F]PSMA‑1007 PET/CT for detecting primary tumors, regional lymph node involvement, and distant metastases in recently diagnosed muscle‑invasive bladder cancer...
PURPOSE: To compare the diagnostic performance of [F]FDG and [F]PSMA‑1007 PET/CT for detecting primary tumors, regional lymph node involvement, and distant metastases in recently diagnosed muscle‑invasive bladder cancer (MIBC). METHODS: Prospective single‑center cohort of six patients (ages 57-82). Both PET/CTs were acquired within 30 days under EANM/SNMMI-conformant protocols, with blinded consensus readings and post-diuretic pelvic acquisitions. RESULTS: [F]PSMA‑1007 identified 15 lesions versus 14 with [F]FDG. Primary bladder lesions were detected in 5 of 6 patients, compared to 3 of 6 patients. Both tracers detected nodal metastases in three patients and bone metastases in one. An [F]FDG‑avid pulmonary lesion near the spleen was not detected with [F]PSMA‑1007 owing to physiological splenic uptake. CONCLUSION: Both tracers showed comparable sensitivity for metastatic disease. The hepatobiliary clearance of [F]PSMA‑1007 improved visualization of intravesical disease, supporting its use in staging and potential theranostic strategies in selected MIBC patients. Such real-world findings inform refinements for future study procedures, logistics, and methodological design, which are essential for minimizing research waste by identifying potential problems early. TRIAL REGISTRATION: Not applicable.
The Binding of the High Affinity Radioligand Fallypride to the D2-dopamine Receptor is Sensitive to Injected Mass - a PET Study in Rodents.
Tóth M, Tari L, Nag S … +7 more , Qiu T, Jia Z, Häggkvist J, Mukherjee J, Varrone A, Halldin C, Farde L
Mol Imaging Biol · 2026 Apr · PMID 41840277 · Full text
PURPOSE: Fallypride is a widely used high affinity radioligand for quantification of D2-dopamine receptor binding in small animal PET imaging. To examine the effect of mass both [F]fallypride and [C]fallypride was inject...
PURPOSE: Fallypride is a widely used high affinity radioligand for quantification of D2-dopamine receptor binding in small animal PET imaging. To examine the effect of mass both [F]fallypride and [C]fallypride was injected in mice over a wide range of molar activity and the binding potential (BP) was compared. PROCEDURES: Eight mice (C57BL/6 J) went through three PET measurements within two weeks. [C]fallypride with the highest possible molar activity (MA) and [F]fallypride with normal and lower molar activity (lowerMA). RESULTS: The binding of [C]fallypride was highest with a BP of 13.5 ± 1.1 BP. The binding of [F]fallypride was lower, 8.6 ± 2.2 BP in the normal condition and 5.3 ± 1.3 BP at the lowerMA condition. By consequence, BP showed a strong negative correlation with injected mass (R2 = 0.95, P < 0.05). Binding data were entered in a Scatchard analysis yielding a B of 62 pmol/g and a K of 0.25 nM. CONCLUSION: In this PET study in mice the average radioligand occupancy was estimated to 19% even for C-labeled fallypride despite the high MA of 153.3 GBq/µmol and low injected mass of 0.03 µg. Therefore, high affinity radioligands should be applied with care in small animal PET studies and radiochemistry has to be at its best to assure that tracer conditions are met in small animal imaging PET imaging.
Magnetically Controlled Nanocarriers for Site-Specific Drug Delivery and Theranostics in Cancer Precision Medicine.
Singh LS, Singh CS, Premlata T
Mol Imaging Biol · 2026 Apr · PMID 41840276 · Publisher ↗
The growing demand for precision oncology has intensified interest in magnetically controlled nanocarriers (MCNCs) as versatile platforms for targeted drug delivery and theranostics. Conventional cancer therapies are oft...
The growing demand for precision oncology has intensified interest in magnetically controlled nanocarriers (MCNCs) as versatile platforms for targeted drug delivery and theranostics. Conventional cancer therapies are often limited by nonspecific drug distribution, systemic toxicity, and poor efficacy against heterogeneous tumors. MCNCs, typically based on superparamagnetic iron oxide nanoparticles and hybrid composites, address these limitations by enabling site-specific accumulation, stimuli-responsive release, and real-time imaging in external magnetic fields. These systems integrate diagnostic and therapeutic functions within a single platform, advancing the concept of image-guided and personalized medicine. Recent advances in surface engineering, biodegradable ferrites, and magnetic-plasmonic hybrids have enhanced their biocompatibility, stability, and multimodal performance. Furthermore, their incorporation into combination therapies, such as magnetic hyperthermia, photothermal therapy, and immunotherapy, has demonstrated synergistic antitumor effects. Despite these advances, translational barriers persist, including challenges in deep tissue targeting, biosafety validation, scalable synthesis, and regulatory standardization. Integrating AI-driven modeling and digital twins can optimize the design, dosing, and magnetic field control for personalized therapy. Collectively, magnetically regulated theranostic nanoplatforms represent a promising frontier in precision cancer medicine, bridging diagnosis, therapy, and real-time monitoring toward safer, more effective, and patient-tailored oncologic care.
Value of Imaging Parameters of [F]FDG PET/CT and Serological Indices in Predicting Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma.
Yan Y, Pang L, He Y … +2 more , Jiang Z, Zhang Y
Mol Imaging Biol · 2026 Apr · PMID 41814042 · Publisher ↗
OBJECTIVE: This study aimed to evaluate the value of [F]FDG PET/CT parameters and serological indices in predicting lymph node metastasis (LNM) in patients with intrahepatic cholangiocarcinoma (ICC) preoperatively. METHO...
OBJECTIVE: This study aimed to evaluate the value of [F]FDG PET/CT parameters and serological indices in predicting lymph node metastasis (LNM) in patients with intrahepatic cholangiocarcinoma (ICC) preoperatively. METHODS: The study included 102 patients with ICC diagnosed between January 2018 and December 2022. All patients underwent preoperative [F]FDG PET/CT scanning and serological marker evaluations before surgical tumor resection. The [F]FDG PET/CT scanning was jointly evaluated by two nuclear medicine physicians blinded to the clinical information and compared with postoperative pathologic results. The tumor SUVmax, tumor-to-background ratios (TBR), SUVpeak, and total lesion glycolysis (TLG) were obtained from the PET/CT scans. Presurgical serological testing included carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). The results were analyzed by bivariate and multivariate logistic regression to develop a prediction model for LNM. RESULTS: Among the 102 patients with ICC, 60 (58.8%) patients had LNM while 42 patients (41.2%) were free of LNM. TBR(without LNM: 6.9 ± 3.6 vs. LNM: 8.2 ± 2.9, P = 0.019), CA19-9(506.9 ± 1602.7 vs. 1901.2 ± 3195.1, P = 0.011) and CEA(5.1 ± 8.9 vs. 32.5 ± 82.7, P = 0.035) in the LNM group were significantly higher than in the without LNM group. Three additional, statistically significant features, tumor TBR > 6.4, CA19-9 > 149.7 U/mL and CEA > 3.2 ng/mL, were integrated into a prediction model, which substantially outperformed use of the single parameter in ROC analysis (AUC 0.802 vs. 0.676, 0.671 and 0.656). CONCLUSION: TBR > 6.4 and CA19-9 > 149.7 U/mL were identified as effective preoperative predictors of LNM in patients with ICC. The prognostic model we propose, integrating imaging parameters and serological indicators, significantly enhances predictive capability.
Photoacoustic Imaging of Muscle Tissue Oxygenation as a Noninvasive Biomarker in Mouse Models of Sickle Cell Disease.
Morin J, Brophy M, Stansfield J … +2 more , Pittman D, Hirenallur-Shanthappa D
Mol Imaging Biol · 2026 Apr · PMID 41811585 · Publisher ↗
PURPOSE: 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. PROCEDURES: In vivo PAI was performed...
PURPOSE: 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. PROCEDURES: 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. RESULTS: 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. CONCLUSIONS: 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.
Malignant Pleural Mesothelioma (MPM) Evaluation with [C]-Methionine PET/CT Before and After Talc Pleurodesis.
Lopci E, Castello A, Testori A … +12 more , Voulaz E, Rahal D, Perrino M, Crepaldi A, Ferraroli GM, Errico V, Bottoni E, Rodari M, Muraglia L, Marulli G, Alloisio M, Zucali PA
Mol Imaging Biol · 2026 Apr · PMID 41801610 · Publisher ↗
BACKGROUND: Malignant pleural mesothelioma (MPM) poses an imaging challenge that requires special attention, especially in patients who have undergone talc pleurodesis. [F]FDG PET/CT (FDG PET) is a validated imaging moda...
BACKGROUND: Malignant pleural mesothelioma (MPM) poses an imaging challenge that requires special attention, especially in patients who have undergone talc pleurodesis. [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 [C]Methionine PET/CT (MET PET) and FDG PET in MPM patients before and after talc pleurodesis. MATERIALS AND METHODS: 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. RESULTS: 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 < 0.01; rho = -0.517, P = 0.013; rho = -0.528, P = 0.011, respectively) and FDG PET (rho = -0.808, P < 0.01; rho = -0.781, P < 0.01; rho = -0.888, P < 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). CONCLUSIONS: 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. CLINICALTRIALS: gov/ ).
Design of a Bifunctional pHLIP-RGD Scaffold for Site-Specific [Tc] Tc Labeling: Radiochemical Evaluation and Proof-of-Concept Tumor Targeting.
Yu M, Chen Y, Yu B … +3 more , Li X, Su Y, Wang Z
Mol Imaging Biol · 2026 Apr · PMID 41781804 · Publisher ↗
PURPOSE: To develop a novel molecular scaffold designed for dual targeting via site-specific [Tc] Tc labeling, we report its radiochemical evaluation and preliminary targeting efficacy in acidic tumor models. PROCEDURES:...
PURPOSE: To develop a novel molecular scaffold designed for dual targeting via site-specific [Tc] Tc labeling, we report its radiochemical evaluation and preliminary targeting efficacy in acidic tumor models. PROCEDURES: The pHLIP-RGD scaffold was synthesized by conjugating pHLIP variant 7 (var7) with cyclo(RGDfK) peptide. Pharmacokinetic assessment of [Tc] Tc-pHLIP-RGD was performed in MDA-MB-231 xenograft-bearing mice through quantitative biodistribution studies and small-animal single photon emission computed tomography (SPECT) imaging. RESULTS: [Tc] Tc-pHLIP-RGD demonstrated high stability in mouse serum for at least 4 h and exhibited strong binding affinity and specificity both in vitro and in vivo. Biodistribution studies revealed rapid tumor accumulation and prolonged retention, with uptake values of 7.01 ± 1.28, 4.23 ± 0.44, 8.04 ± 0.63, and 9.60 ± 1.26%ID/g at 0.5, 1.0, 2.0, and 4.0 h post-injection, respectively. Off-target accumulation was primarily observed in the liver. In blocking studies, the administration of non-radioactive pHLIP-RGD partially reduced tumor uptake of [Tc] Tc-pHLIP-RGD, with tumor distribution values at 0.5, 1.0, 2.0, and 4.0 h of 4.66 ± 0.49, 3.25 ± 0.36, 3.04 ± 1.15, and 3.75 ± 0.57%ID/g, respectively. SPECT imaging findings were consistent with biodistribution data, showing clear visualization of tumors at all time points. Tumor visibility was significantly reduced in the blocking study, with a corresponding increase in liver uptake. CONCLUSIONS: The heterodimeric radiotracer [Tc] Tc-pHLIP-RGD exhibited high radiochemical yield, good stability, and favorable tumor uptake and retention characteristics. These proof-of-concept results suggest the potential of the dual-targeting design strategy for developing diagnostic imaging agents for triple-negative breast cancer (TNBC).
Sonodynamic Therapy-Enhanced Immunotherapy for Triple-Negative Breast Cancer: Mechanistic Advances, Nanoplatform Strategies, and Clinical Prospects.
Tatiparthi R, Panda A, Chaitanya M … +3 more , Gashe F, Hasan G, Yarlagadda R
Mol Imaging Biol · 2026 Apr · PMID 41781803 · Publisher ↗
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 gener...
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.
Engineering Anti-MMP-9 Peptide-Modified Nanoparticles for Precision MRI Diagnosis of Endometriosis.
Zhang Q, Li H, Xu L … +7 more , Wu S, Shen Y, Wang Y, Guo X, Zhu Q, Ruan X, Zhang J
Mol Imaging Biol · 2026 Apr · PMID 41760802 · Publisher ↗
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...
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 NaGdF@PEG-Cy5.5 nanoparticles (NPPCNs), which integrate NaGdF 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.
Value of Multitracer Imaging in Hepatocellular Carcinomas with Different Metastatic Potential.
He T, Zhang C, Zhang J … +2 more , Zhang X, Wang R
Mol Imaging Biol · 2026 Apr · PMID 41735739 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) shows marked heterogeneity and varying metastatic potential, challenging prognosis and treatment. This study evaluated multitracer PET imaging with [F]FDG, [F]FLT, and [F]ACE to...
BACKGROUND: Hepatocellular carcinoma (HCC) shows marked heterogeneity and varying metastatic potential, challenging prognosis and treatment. This study evaluated multitracer PET imaging with [F]FDG, [F]FLT, and [F]ACE to differentiate HCCs by metastatic behavior and explored its prognostic relevance. METHODS: 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. RESULTS: Tracer uptake significantly differed among cell lines (p < 0.001). The triple-tracer model ([F]FDG + [ F]FLT + [F]ACE) yielded the lowest classification error rate (0.074) compared with dual tracers (0.085-0.362). In vivo, [F]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.[F]FLT uptake showed moderate correlation with biomarkers but not with survival, while [F]ACE had no significant discriminative value. CONCLUSIONS: 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. [F]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.
Imaging vascular characteristics and glycolytic metabolism of glioblastoma in a chick embryo model using H MRI and [F]FDG-PET.
Gash EN, Schulze J, Barnett SE … +9 more , Maguire ML, Batie M, Moothanchery M, Pickup S, Scott I, Zakaria R, Coulson JM, Rocha S, Poptani H
Mol Imaging Biol · 2026 Apr · PMID 41731278 · Full text
PURPOSE: To assess hypoxia-associated host-tumour vascular adaptations and glycolytic metabolism in the chick chorioallantoic membrane (CAM) glioblastoma model. PROCEDURES: U251 GBM cells were conditioned under normoxia...
PURPOSE: To assess hypoxia-associated host-tumour vascular adaptations and glycolytic metabolism in the chick chorioallantoic membrane (CAM) glioblastoma model. PROCEDURES: 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 [F]FDG-PET on E12 followed by lactate MRS on E13 (n = 8). RESULTS: 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 [F]FDG uptake and lactate signal. However, no statistically significant relationship was observed between the two methods. CONCLUSIONS: 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 [F]FDG uptake and lactate were measurable, no significant correlation between the two was observed, potentially reflecting variability in tumour engraftment, vascular delivery of [F]FDG, and microenvironmental influences on lactate accumulation.
Template-Directed RIG-I Agonist Assembly for Image-guided Targeted Cancer Immunotherapy.
Ghosh SK, Lazarus D, Robertson N … +6 more , Liu QP, Kenyon E, Mallett CL, Chen M, Medarova Z, Moore A
Mol Imaging Biol · 2026 Apr · PMID 41714538 · Full text
PURPOSE: 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 recepto...
PURPOSE: 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. PROCEDURES: 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. RESULTS: 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. CONCLUSIONS: 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.
Theranostic and Radionuclide-based Treatment Approaches for Radioiodine-refractory Thyroid Cancer: From Biology to Clinical Application.
Arawker MH, Habibullah F, Fu L … +2 more , Baral S, Qiu X
Mol Imaging Biol · 2026 Apr · PMID 41708943 · Publisher ↗
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 mut...
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 Lu and Ac-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.
Exploration of the Feasibility of One-Day Dual-Low-Activity Ga-DOTATATE and F-FDG PET/MR in Patients with Neuroendocrine Neoplasms.
Zhao W, Pang L, Xie Y … +2 more , Tang W, Shi H
Mol Imaging Biol · 2026 Apr · PMID 41680383 · Publisher ↗
PURPOSE: 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 Ga-DOTATATE and F-FDG dual-low-activity PET/MR imaging in...
PURPOSE: 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 Ga-DOTATATE and F-FDG dual-low-activity PET/MR imaging in patient with neuroendocrine neoplasms (NENs). PROCEDURES: Fourteen NENs patients who underwent 1-day Ga-DOTATATE and F-FDG dual-low-activity PET/MR, and another 14 patients matched with the same primary tumor sites and tumor grades who underwent 2-day Ga-DOTATATE and F-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 Ga-DOTATATE PET, F-FDG PET and PET/MR, respectively. RESULTS: 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 Ga-DOTATATE PET (median [IQR]: 3[2-3] vs. 3[2-3]), F-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). CONCLUSION: The 1-day Ga-DOTATATE and F-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.
Enhanced Fluorescence of Near-Infrared Anti-CEA Antibodies for Visualizing Colorectal Cancers Using Modified Heptamethine Cyanines.
Cox K, Jitender J, Mehta S … +8 more , Li DH, Amirfakhri S, Hoffman RM, Shively J, Yazaki P, Schnermann MJ, Bouvet M, Lwin TM
Mol Imaging Biol · 2026 Apr · PMID 41667902 · Full text
BACKGROUND: 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 phar...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Molecular Imaging of Macrophages in Cardiovascular Diseases.
Xu J, Sun W, Zhang X … +8 more , Xiong Y, Qiu J, Gao T, Cao H, Zhang L, Xie M, Lv Q, Wu W
Mol Imaging Biol · 2026 Apr · PMID 41652130 · Publisher ↗
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 quanti...
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.
A Bioimaging Study of Zr-Bintrafusp Alfa PET Scans in Patients with Advanced or Metastatic NSCLC Receiving Bintrafusp Alfa Alone or in Combination with Chemotherapy.
Gan HK, Parakh S, Lee ST … +9 more , O'Keefe GJ, Palmer J, Mathai J, Smith V, Wichmann CW, McDonald AF, Guo N, Scott FE, Scott AM
Mol Imaging Biol · 2026 Feb · PMID 41462000 · Publisher ↗
RATIONALE: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (TGF-βRII or TGF-β "trap") and human immunoglobulin 1...
RATIONALE: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (TGF-βRII or TGF-β "trap") and human immunoglobulin 1 antibody which blocks programmed cell death ligand 1 (PD-L1). This trial aimed to investigate the biodistribution of Zr-bintrafusp alfa in patients with NSCLC with PD-L1 expressing tumors. METHODS: Five lung cancer patients were recruited with PD-L1 staining more than 1% of tumor cells. Patients underwent Zr-bintrafusp alfa intravenous infusion (100 mg IV) on Day 1 followed by sequential PET imaging to determine the biodistribution of Zr-bintrafusp alfa. Patients then received treatment with bintrafusp alfa (1200 mg IV) on day 15 and 29, with the latter including further Zr-bintrafusp alfa to determine the effects of bintrafusp alfa treatment on receptor occupancy. Patients continued with bintrafusp alfa monotherapy, or in combination with chemotherapy for those without objective response to monotherapy, until disease progression or unacceptable toxicity. The study stopped after five patients due to the overall cessation of the bintrafusp alfa program. RESULTS: Zr-bintrafusp alfa imaging was feasible and well tolerated. All patients showed tumor specific uptake without normal tissue uptake. There was no correlation between uptake and tissue PD-L1 expression or outcomes, likely due to sample size. Inter- and intra-patient heterogeneity was observed and optimal treatment regimens will need to address this in future. CONCLUSIONS: Zr-bintrafusp alfa imaging is safe, feasible and provides relevant tumor targeting information for patient selection and treatment.
Preliminary Results on the Added Value of Parametric Images Derived from F-fluoroethyl-L-tryptophan PET for Posttreatment Glioblastoma Assessment.
Juhász C, Barger GR, Dominello M … +4 more , Robinette NL, Chamiraju P, Jiang H, Muzik O
Mol Imaging Biol · 2026 Feb · PMID 41430029 · Full text
BACKGROUND: Increased amino acid transport in gliomas allows imaging of metabolically active tumor volume by PET. Tryptophan analog PET radiotracers can provide additional information by tracking tumoral metabolism via t...
BACKGROUND: Increased amino acid transport in gliomas allows imaging of metabolically active tumor volume by PET. Tryptophan analog PET radiotracers can provide additional information by tracking tumoral metabolism via the upregulated immunosuppressive tryptophan-kynurenine pathway. We tested the recently developed tryptophan analog PET tracer [F]-fluoro-ethyl-L-tryptophan ([F]FETrp) for detecting post-treatment glioblastoma while using a non-invasive approach to generate parametric tryptophan metabolic maps and comparing them with static tracer uptake maps and contrast-enhanced MRI. METHODS: Five patients (age: 22-67 years) with previously treated glioblastoma underwent [F]FETrp PET/CT imaging. A dynamic acquisition protocol sampled the brain and blood pool non-invasively using the FlowMotion Multiparametric PET software (Siemens Healthineers). Parametric brain images of the unidirectional uptake rate constant (K), characterizing irreversible tryptophan trapping and the volume of distribution (V) were fused with static uptake (SUV) maps and contrast-enhanced brain MRI. Voxels with elevated K, V, and SUV were defined, and their spatial associations with contrast-enhanced volumes were characterized by their % volume overlap and the distance between their centroids. RESULTS: A substantial spatial volume overlap was observed between MRI contrast-enhancing regions and elevated static [F]FETrp uptake and V. In contrast, the overlap between contrast-enhancing regions and elevated K metabolic volumes was low (0-16%), with high K areas extending deeper into non-enhancing brain (7-33 mm centroid distance). These non-enhancing high K areas showed new contrast-enhancement on follow-up MRI, consistent with tumor progression. CONCLUSIONS: Areas of high tryptophan metabolism detected by [F]FETrp PET-derived parametric (K) maps extend outside the contrast-enhancing glioblastoma mass in adjacent non-enhancing brain regions that can be missed or underestimated by static uptake images. Consequently, [F]FETrp PET metabolic maps have the potential for enhanced detection of non-enhancing glioma infiltration for improved radiation or surgical treatment planning.
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