Mol Imaging Biol [JOURNAL]
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200 papers
PET Study of S1PR1 Expression in Rodent Model of Myocardial Infarction.
Chen H, Qiu L, Jiang H … +6 more , Zhou W, Soda AK, Kovacs A, Weinheimer CJ, Gropler RJ, Tu Z
Mol Imaging Biol · 2025 Oct · PMID 40770597 · Full text
PURPOSE: Acute myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator influencing numerous physiological processes. S1PR1 is the pr...
PURPOSE: Acute myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator influencing numerous physiological processes. S1PR1 is the predominant isoform of the S1P receptor in cardiomyocytes and vascular endothelial cells. S1PR1 plays a critical role in preventing adverse cardiac remodeling. The importance of S1PR1 in cardiac physiology has led to the development of novel treatments for MI, including S1PR1 gene delivery strategies aimed at preventing heart failure. Monitoring the dynamic changes of S1PR1 post-MI is clinically significant for assessing cardiac remodeling. This study validated the ability of specific S1PR1 PET radiotracer [F]FS1P1 to track changes in this signaling pathway, thereby providing a non-invasive diagnostic tool to quantify S1PR1 expression for investigating MI in vivo. PROCEDURES: We characterized the S1PR1 radiotracer [F]FS1P1 in an echo-guided mouse model of MI. [F]FDG PET was used to delineate the infarct area. Masson trichrome staining was used to identify cardiac fibrosis. Immunofluorescence (IF) experiment was conducted to demonstrate changes in S1PR1 expression after MI. Autoradiography was performed to evaluate the distribution of [F]FS1P1 in MI heart tissues. MI (n = 4) and sham (n = 4) mice were scanned with [F]FS1P1 PET at 2 days and 2 weeks post-MI, radioactivity uptake in the myocardium was calculated as the percentage of the injected dose per gram (%ID/g). RESULTS: The uptake of [F]FS1P1 was significantly decreased by 31.8% in the infarct region at 2 days post-MI compared to the sham group (1.3 ± 0.3 vs. 1.9 ± 0.3), and decreased by 37.6% at 2 weeks post-MI (1.2 ± 0.5). Additionally, [F]FS1P1 signal decreased by 20.8% in the non-infarct remote area at 2 weeks post-MI compared with the sham control (1.6 ± 0.4 vs. 2.0 ± 0.2). Autoradiography study confirmed the trend of decreased [F]FS1P1 uptake in the MI tissues. IF studies confirmed that the change in the [F]FS1P1 PET signal corresponded with the change in S1PR1 expression. CONCLUSIONS: This study demonstrated the downregulation of S1PR1 expression following MI and validated the use of [F]FS1P1 PET imaging as an effective tool for detecting changes in S1PR1 expression post-MI.
Development and Evaluation of a Vinyl Sulfone-Based Fluorine-18 Labeling Method for Constructing PSMA-targeted Prostate Cancer Imaging Agents.
Wang C, Long R, Hu M … +7 more , Zhou L, Ding H, Zhao W, Huang Z, Chen Y, Li Z, Wang L
Mol Imaging Biol · 2025 Oct · PMID 40715723 · Publisher ↗
PURPOSE: Since prostate-specific membrane antigen (PSMA) is widely expressed in nearly all stages of prostate cancer (PCa), PSMA tracers can be considered a viable diagnostic tool for PCa. Compared to Ga-labeled PSMA age...
PURPOSE: Since prostate-specific membrane antigen (PSMA) is widely expressed in nearly all stages of prostate cancer (PCa), PSMA tracers can be considered a viable diagnostic tool for PCa. Compared to Ga-labeled PSMA agents, F-labeled analogues have various advantages, including the ability to achieve large scale production; easy to commercialize due to its longer half-life; and the ability to image late time points. Because [F]vinyl sulfone (VS) is a good intermediate for labeling thiol groups in mild conditions with high labeling yield, we explored the use of various VS groups for PSMA modifications in this study. PROCEDURES: We developed six F-labeled radiotracers targeting PSMA from radioactive intermediates to explore targeting ability and distribution in vivo in LNCaP and 22RV1 tumor-bearing mice. Different labeling methods were compared on their ability to lead to PSMA agents with high contrast and uptake. RESULTS: In vitro stability assay showed that the tracer [F]4a had high stability, with more than 95% of the radiochemical purities remaining as intact forms after 0.5, 1, and 2 h incubation, respectively. In vitro binding assays showed that [F]4a has a low-micromole binding affinity of 9.45 µM. Cell uptake and internalization assays found that [F]4a exhibited the highest cell uptake and internalization in 22RV1 cells (1.25 ± 0.06, 1.32 ± 0.11, 1.73 ± 0.08, and 2.03 ± 0.14%ID/10 cells after 10 min, 30 min, 1 h, and 2 h incubation, respectively for cell uptake assay; 0.52 ± 0.02, 0.70 ± 0.11, 0.78 ± 0.04, and 0.98 ± 0.15%ID/10 cells after 10 min, 30 min, 1 h, and 2 h incubation, respectively for cell internalization assay.) Analysis of the PET images showed that the tracer [F]4a had the highest tumor uptake (3.38 ± 0.35%ID/g at 2 h p. i. in 22RV1 tumor-bearing mice; 30.16 ± 13.00%ID/g at 2 h p. i. in LNCaP tumor-bearing mice.) Of note, the tracer [F]4a showed an approximately threefold increase in tumor uptake compared to [Ga]PSMA-11 in LNCaP tumor-bearing mice at 2 h p. i. The biodistribution experiment verified the accuracy of the in vivo distribution of [F]4a in LNCaP and 22RV1 tumor-bearing mice by PET/CT imaging. CONCLUSIONS: PSMA-targeted radiotracer [F]4a is a promising PET agent for prostate cancer diagnosis.
Preclinical Evaluation of Novel SGLT2-Targeted Near-Infrared Optical Imaging Agent for Early-Stage Pulmonary Adenocarcinoma.
Ortmeyer Welch K, McGovern KA, Chen L … +9 more , Krouse R, Guo K, Huang J, Brown M, Mlakar J, Bandi V, Holt D, Zhang P, Singhal S
Mol Imaging Biol · 2025 Aug · PMID 40659959 · Full text
PURPOSE: Lung cancer is increasingly diagnosed at early stages, but intraoperative localization of early lesions remains challenging. Intraoperative molecular imaging (IMI) aids in localization of tumors during surgery;...
PURPOSE: Lung cancer is increasingly diagnosed at early stages, but intraoperative localization of early lesions remains challenging. Intraoperative molecular imaging (IMI) aids in localization of tumors during surgery; however, no optical agents are targeted specifically for early-stage lesions. The sodium-glucose cotransporter 2 (SGLT2) has been implicated in early lung carcinogenesis. This study aimed to describe SGLT2 expression in early-stage lung adenocarcinoma (LUAD) and develop and validate a novel SGLT2-targeted near-infrared (NIR) contrast agent, GlucoGlo, for imaging LUAD. PROCEDURES: SGLT2 expression was confirmed by immunohistochemistry (IHC) in human samples. GlucoGlo optical properties were characterized and compared to common NIR dyes. Sensitivity and specificity for SGLT2 were assessed using preclinical in vitro and in vivo mouse models. RESULTS: On IHC, stage I LUAD displayed higher SGLT2 expression than stage II-III LUAD and normal lung tissue. GlucoGlo exhibited similar depth of penetration and resolution to FDA-approved contrast agents. SGLT2-expressing cell lines treated with GlucoGlo displayed higher fluorescence than the control cell line, confirming SGLT2-dependent uptake. Fluorescence increased with both incubation time and GlucoGlo concentration. Glucose and unconjugated GlucoGlo ligand competitively inhibited GlucoGlo in a dose-dependent manner, indicating high affinity and specificity. GlucoGlo selectively accumulated in SGLT2-expressing flank xenografts, with mean SBR of 2.23 and was inhibited by pretreatment with unconjugated GlucoGlo ligand. CONCLUSIONS: These findings support the potential of GlucoGlo as a targeted IMI contrast agent for early-stage LUAD, and they provide a foundation for future in vivo studies and translational development.
Local Infusing Antiplatelet Microspheres to Prevent Thrombosis Post-PCI: a Feasibility Study in Rabbit Aorta.
Peng Y, Liu K, Tian W … +5 more , Shi T, Lin Q, Tian Y, Li R, Meng Y
Mol Imaging Biol · 2025 Aug · PMID 40634660 · Publisher ↗
PURPOSE: After percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is required to prevent thrombosis, but systemic DAPT may increase bleeding risk. This study aimed to develop a new concept of anti...
PURPOSE: After percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is required to prevent thrombosis, but systemic DAPT may increase bleeding risk. This study aimed to develop a new concept of antiplatelet therapy administered via local infusion of PLGA-FeO-ticagrelor microspheres (PFTm). PROCEDURES: PLGA loaded with FeO and ticagrelor magnetic microspheres were constructed. In vitro study, the morphology, relaxation rate, drug release rate, encapsulation efficiency, and biocompatibility of PFTm were evaluated. In vivo study, vascular injury model of rabbit abdominal aorta was established by Fogarty balloon. The injured rabbit aorta wall was infused PFTm by infusion balloon in the local PFTm therapy group, while the rabbit was injected PFTm intravenously in the systemic PFTm therapy group. The non-therapy control group and healthy control group did not receive PFTm treatment. MR T2WI was performed pre-operation, post-operation to detect PFTm distribution. Then, the targeted abdominal aorta segments were harvest for pathological examination. RESULTS: The PFTm was spherical with a size of 930.5 ± 134 nm and SPAN was 0.35. The ticagrelor encapsulation efficiency was 82% ± 2%, and the release rate reached 88% ± 2% within 96 h. The r2 of the PFTm was 332.0 mM s. All rabbits were successfully established abdominal aorta injury model. MRI showed significant decrease of SNR in aortic wall which represented PFTm infused into aortic wall. Pathology showed that local thrombus was significant inhibited in the local PFTm therapy group compared with the other groups. CONCLUSIONS: The new concept of releasing drugs in a sustained manner for local antiplatelet therapy after PCI was successfully established.
Combining Dopamine Transporter and Amyloid PET Tracer: A Preclinical Study on Dual-Target Imaging.
Park BN, Kim SM, An YS
Mol Imaging Biol · 2025 Aug · PMID 40629207 · Publisher ↗
PURPOSE: This study aimed to evaluate the feasibility and diagnostic utility of a dual-target positron emission tomography (PET) imaging approach using a cocktail of N-3-[F]fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)...
PURPOSE: This study aimed to evaluate the feasibility and diagnostic utility of a dual-target positron emission tomography (PET) imaging approach using a cocktail of N-3-[F]fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([F]FP-CIT) and [F]florbetaben (FBB) for the simultaneous assessment of dopaminergic and amyloid changes in a preclinical setting. PROCEDURES: We utilized both Parkinson's disease (PD) and Alzheimer's disease (AD) mouse models, as well as a control group, to investigate the uptake of [F]FP-CIT and [F]FBB individually and in combination. PET imaging was conducted, and standardized uptake value ratios (SUVRs) were analyzed for each model across the striatal and cortical regions. Comparisons were made between single and cocktail PET scans to assess potential cross-interference of the tracers. RESULTS: In both PD and AD models, no statistically significant differences were observed in the SUVRs between single-tracer and cocktail PET scans in the striatum and cortex (p > 0.4 for striatal comparisons, p > 0.8 for cortical comparisons). Bland-Altman analysis showed no significant bias, supporting the interchangeability of SUVRs between single and cocktail PET scans. CONCLUSIONS: This preclinical study suggests that [F]FP-CIT and [F]FBB PET imaging is a viable dual-target imaging approach for neurodegenerative disease evaluation. The method could streamline diagnostic workflows and improve patient convenience. Further clinical studies are warranted to validate the efficacy and safety of this approach in human populations.
F MR Imaging of Dule Lung Cancer Models with Two Administration Methods of PFC Nanoparticles.
Liu F, Shao M, Xu X
Mol Imaging Biol · 2025 Aug · PMID 40629206 · Publisher ↗
BACKGROUND: Pulmonary delivery of agents to lung is an effective method for the diagnosis and therapy of lung cancer. PURPOSE: To demonstrate that pulmonary delivery of perfluorocarbon (PFC) nanoparticles for orthotopic...
BACKGROUND: Pulmonary delivery of agents to lung is an effective method for the diagnosis and therapy of lung cancer. PURPOSE: To demonstrate that pulmonary delivery of perfluorocarbon (PFC) nanoparticles for orthotopic lung tumor model is better than intravenous injection for subcutaneous tumor, and to confirm that the nanoparticles can be uptaked by tumor tissue which showed by F MR imaging and tissue staining. METHODS: We detected the targeted ability of folate receptor (FR) targeted PFC nanoparticles with H460 cells in vitro. Subcutaneous and orthotopic lung cancer models were established. When the tumors could be detected by MR after two weeks, PFC nanoparticles were administrated intratracheally in orthotopic group and intravenously in subcutaneous group. F MR scanning was performed in mice models at before and different time points (4, 24, and 48 h) after delivery. Mice were euthanized after MR imaging, and tumor tissues were taken out, HE and fluorescent staining were performed respectively. In addition, orthotopic tumor tissue was obtained for transmission electron microscopy (TEM) examination. RESULTS: The orthotopic tumor model showed a significant F MRI enhancement effect in the tumor region after PFC nanoparticles delivered intratracheally than subcutaneous model. As time went on, the accumulation of nanoparticles in the tumor area increased, and the F signal increased gradually. The F SNR in the tumor region of orthotopic group was significantly higher than that of subcutaneous group at 24 and 48 h after delivery (p < 0.001). Histological experiments showed that PFC nanoparticles accumulated in the tumor region especially in orthotopic group. CONCLUSION: Pulmonary delivery of PFC nanoparticles is a novel and effective method for orthotopic lung cancer xenograft model, and the PFC nanoparticles can be detected by F MR imaging in vivo.
Positive Protective Effects of Sigma-1 Receptor Stimulation with Fluvoxamine after Myocardial Ischemia and Reperfusion in Rats.
Zhang X, Wakabayashi H, Mori H … +6 more , Hiromasa T, Chen Z, Kozaka T, Ogawa K, Kinuya S, Taki J
Mol Imaging Biol · 2025 Aug · PMID 40610697 · Full text
BACKGROUND: The sigma-1 receptor (Sig-1R) plays diverse roles in regulating Endoplasmic Reticulum (ER) stress, calcium handling, and ion channel activity under pathological conditions, offering cardioprotective effects i...
BACKGROUND: The sigma-1 receptor (Sig-1R) plays diverse roles in regulating Endoplasmic Reticulum (ER) stress, calcium handling, and ion channel activity under pathological conditions, offering cardioprotective effects in pressure overload-induced dysfunction. However, its role in post-myocardial ischemia damage remains unclear. This study evaluated the cardioprotective effects of Sig-1R activation by fluvoxamine following myocardial ischemia in rats. METHOD AND RESULTS: Wistar rats underwent 20 min of coronary artery occlusion followed by reperfusion. Rats received either saline (control) or fluvoxamine for two weeks. ECG-gated SPECT with Tc-MIBI was performed on days 1, 14, and 28 post-reperfusion to measure the end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), and summed rest score (SRS). Autoradiography and histological analyses were performed on day 29. Fluvoxamine significantly improved LVEF after two weeks (D14-D1: 6 ± 7, p = 0.03), with the improvement persisting to the 28th day (8 ± 5, p < 0.01). Autoradiography revealed a smaller non-salvaged area (0.15 ± 0.19 vs. 0.42 ± 0.32, p < 0.05) and more salvaged myocardium (0.33 ± 0.13 vs. 0.14 ± 0.14, p < 0.05) in the fluvoxamine group. Histology showed less fibrosis (0.06 ± 0.05 vs. 0.11 ± 0.08, p < 0.05) and reduced macrophage infiltration (0.08 ± 0.05 vs. 0.16 ± 0.08, p < 0.001) with fluvoxamine. CONCLUSIONS: Sig-1R stimulation by fluvoxamine suppresses LV remodelling and enhances LVEF recovery post-ischemia, suggesting its potential as a novel cardioprotective strategy.
MIB guides: [Zr]Zr-DFO-trastuzumab and [Cu]Cu-NOTA-Trastuzumab for Preclinical Cancer Imaging.
Simó C, Vanover AC, Azevedo EC … +1 more , Pereira PMR
Mol Imaging Biol · 2025 Aug · PMID 40571804 · Full text
Radiopharmaceuticals based on antibody biomolecules are widely used in oncology for positron emission tomography (PET). Trastuzumab, an antibody that targets the epidermal growth factor receptor 2 (HER2), has been extens...
Radiopharmaceuticals based on antibody biomolecules are widely used in oncology for positron emission tomography (PET). Trastuzumab, an antibody that targets the epidermal growth factor receptor 2 (HER2), has been extensively studied for both preclinical and clinical cancer imaging. This MIB guide specifically focuses on the radiolabeling of the antibody trastuzumab with zirconium-89 (Zr) and copper-64 (Cu) for PET imaging. The guide describes the steps for conjugating trastuzumab with p-SCN-Bn-deferoxamine (DFO) or 2,2',2''-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (p-SCN-Bn-NOTA) chelators through conjugation between the isothiocyanate (-SCN) functional group on the chelator with lysines on the trastuzumab. We also describe subsequent radiolabeling steps with Zr or Cu. The steps described here can be adapted to the radiolabeling of other antibodies upon protocol optimization.
Diagnostic Value of [F]-FDG and [ Ga]-FAPI-04 PET/MRI for Lymph Node Metastasis in Papillary Thyroid Cancer.
Han T, Quan Z, Wei H … +7 more , Zhang M, Ye J, Li G, Wang J, Ma T, Wang J, Kang F
Mol Imaging Biol · 2025 Aug · PMID 40555936 · Publisher ↗
PURPOSE: This study aimed to evaluate the diagnostic value of [F]-FDG PET/MRI for the diagnosis of neck lymph node metastasis (LNM) in patients with initially diagnosed papillary thyroid cancer (PTC) and to compare it wi...
PURPOSE: This study aimed to evaluate the diagnostic value of [F]-FDG PET/MRI for the diagnosis of neck lymph node metastasis (LNM) in patients with initially diagnosed papillary thyroid cancer (PTC) and to compare it with [ Ga]-FAPI-04 PET/MRI. METHODS: Thirty patients with PTC confirmed by thyroid fine-needle aspiration biopsy were prospectively enrolled and underwent [F]-FDG PET/MRI; of which, 6 additionally underwent [ Ga]-FAPI-04 PET/MRI within 3 days. According to surgical guidelines, the neck lymph node (LN) was divided into three macroscopic regions: central (VI) and left/right lateral neck (II-V). Images were semi-quantitatively and visually interpreted, and lesions' quantity, location, and uptake values were noted. Diagnostic performance of [F]-FDG PET/MRI versus US and MRI in N-staging of PTC patients based on regional analysis using postoperative histopathology as the gold standard. Whether the BRAF mutation or not affects metastatic LN radioactivity uptake. Exploring the relevance of dual tracer imaging of metastatic LN radioactivity uptake and its head-to-head comparison for diagnostic efficacy. RESULTS: A total of 48 macroscopic regions were surgically dissected. In terms of predicting LNM, the diagnostic efficacy of [F]-FDG PET/MRI for detecting LNM was higher than that of US and MRI, overall sensitivity, specificity, and accuracy were 71.1% vs. 60.5% vs. 65.8%, 90.0% vs.80.0% vs. 80.0%, and 75.0% vs. 64.6% vs. 68.8%, respectively (all P > 0.05). SUV of metastatic LNs on [ Ga]-FAPI-04 PET/MRI was positively correlated with [F]-FDG PET/MRI (r = 0.8564, 95%CI: 0.7208-0.9289; P < 0.0001). BRAF mutation had no significant effect on the [F]-FDG uptake level and TBR value in metastatic LN of PTC (SUV: 2.5 ± 2.3 vs. 2.2 ± 1.1; TBR: 2.9 ± 2.6 vs. 2.6 ± 1.4; all P > 0.05). The positive lesion detection rate of dual tracer imaging in 6 patients with PTC is consistent, and the degree of radioactivity uptake of [ Ga]-FAPI-04 was higher than that of [F]-FDG in both primary lesion and LNM (12.3 ± 5.7 vs. 6.9 ± 5.3;4.5 ± 3.7 vs. 3.4 ± 1.8; all P > 0.05). CONCLUSION: [⁸F]-FDG PET/MRI demonstrated marginally superior diagnostic performance for LNM detection compared to US and MRI, but all three modalities exhibited suboptimal sensitivity, particularly in the central region. Small sample populations revealed no significant differences in [ Ga]-FAPI-04 and [F]-FDG uptake levels in primary lesion and LNM of PTC, but relatively lower nonspecific uptake of [ Ga]-FAPI-04 pharyngeal lymphatic ring may have the potential to reduce diagnostic error in specific diseases.
Poor Diagnostic Performance of the Melanin-Binding Tracer [18 F]MEL050 in Human Melanoma Indicates Biological Heterogeneity.
Ware RE, Kee D, Roselt P … +10 more , Greguric I, Katsifis A, Bourdier T, Noonan W, Murray W, Mitchell C, Downes M, Shackleton M, McArthur GA, Hicks RJ
Mol Imaging Biol · 2025 Aug · PMID 40537707 · Full text
PURPOSE: Malignant melanoma is a highly lethal malignancy typically characterized by the expression of melanin, which is an attractive diagnostic and therapeutic target in these cancers because it is expressed in few oth...
PURPOSE: Malignant melanoma is a highly lethal malignancy typically characterized by the expression of melanin, which is an attractive diagnostic and therapeutic target in these cancers because it is expressed in few other tissues. Following preclinical evaluation of the melanin-targeting PET tracer, [18F]-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide ([18F]MEL050), we sought to evaluate this agent in patients with melanoma. METHOD: A phase I clinical trial was performed in ten patients with metastatic melanoma. Safety, dosimetry and diagnostic performance of intravenously administered][18F]MEL050 were evaluated. Based on results from this trial, we further assessed the prevalence and prognostic significance of loss of melanin expression in two historical patient cohorts for which there were matching histological and clinical outcome data. RESULTS: Across the trial cohort, no adverse safety signals resulted from [18F]MEL050 administration. The whole-body effective dose was 0.0163 mSV/MBq for an adult male and 0.0206 mSV/MBq for an adult female. The human biodistribution was favorable with low uptake in organs at high risk of metastatic spread, including the brain. Of metastatic sites identified as melanoma on [18F]FDG PET/CT, only 31/65 (48%) were positive on [18F]MEL050 PET. Four [18F]FDG+[18F]MEL050+ metastases were resected from three patients and found to be melanotic by histological examination, whereas five [18F]FDG+[18F]MEL050- metastases from two patients were amelanotic. In our historical cohorts, amelanosis was more common in metastatic than primary disease (45% versus 20%) and the presence of melanin within sentinel lymph node metastases was associated with worse disease-free (HR 2.3 95% CI 1.3 - 4.3, p = 0.002) and disease-specific survivals (HR 3.6, 95% CI 1.4 - 9.7,p = 0.009) in stage III disease, compared with amelanotic sentinel lymph node metastases. CONCLUSION: We propose caution in the use of melanin-targeted agents for melanoma diagnosis and therapy until their utility as prognostic or predictive imaging biomarkers, and the biological implications of loss of melanin deposition during melanoma progression, are better understood.
Preclinical Evaluation of a Near-Infrared Labelled Antibody Targeting the Tumour Associated Xenoantigen N-Glycolyl-Neuraminic Acid GM3 Ganglioside.
Barreto K, Bernhard W, Toledo D … +4 more , Jett K, Casaco A, León K, Geyer CR
Mol Imaging Biol · 2025 Aug · PMID 40526182 · Full text
PURPOSE: Targeted and broadly applicable molecular targets are important for image guided surgery. Xenoantigens represent a particularly interesting class of targets. This study evaluates the xenoantigen N-glycolyl-neura...
PURPOSE: Targeted and broadly applicable molecular targets are important for image guided surgery. Xenoantigens represent a particularly interesting class of targets. This study evaluates the xenoantigen N-glycolyl-neuraminic acid GM3 ganglioside (Neu5Gc-GM3) as a potential fluorescence-guided surgical tool. PROCEDURES: The antibody 14F7hT is conjugated to the near-infrared dye (IRDye800CW) and characterized under GLP conditions. The quality and stability of the 14F7hT-IRDye800CW probe was assessed. In vivo imaging using 14F7hT-IRDye800CW in mice with Neu5Gc GM3 positive and negative xenografts were compared to a control IgG-IRDye800CW probe targeting an epitope not present on the xenografts. Biodistribution, pharmacokinetics, and toxicity were evaluated. RESULTS: The 14F7hT-IRDye800CW probe was 98 ± 2% pure as determined by micro-capillary electrophoresis. The KDapp as determined by binding cell-lines expressing the target was unchanged after conjugation. We demonstrate a peak accumulation window of 12 - 48 h in murine xenografts with male and female CD-1 nude mice administered 0.5 nmoles of the probe (i.v.) and very low uptake in other tissues. Preclinical toxicity studies in male and female balb/c mice support a no observed adverse effect level (NOAEL) of 50 mg/kg in mice. CONCLUSIONS: The 14F7hT-IRDye800CW probe was found to be safe and have low non-specific uptake in a model organism known to express the target. These data support future clinical development of the probe.
One-step Radiosynthesis and Preclinical Evaluation of Molecular Tracer [F]FEtO-CHC Targeting Monocarboxylate Transporters for PET Imaging in Tumor-bearing Mice.
Shi D, Liu L, Zhang D … +10 more , Zheng Y, Hu W, Wu P, Hao X, Liu H, Gao J, Li J, Wu Z, Li S, Wang H
Mol Imaging Biol · 2025 Aug · PMID 40500556 · Publisher ↗
PURPOSE: Monocarboxylate transporters (MCTs) play a pivotal role in tumor metabolic symbiosis, acid resistance, and metastatic progression. Herein, we report the development of [F]FEtO-CHC, a novel MCTs-targeted positron...
PURPOSE: Monocarboxylate transporters (MCTs) play a pivotal role in tumor metabolic symbiosis, acid resistance, and metastatic progression. Herein, we report the development of [F]FEtO-CHC, a novel MCTs-targeted positron emission tomography (PET) radiotracer, and systematically evaluate its potential for non-invasive tumor imaging. PROCEDURES: The radiosynthesis of [F]FEtO-CHC and its non-radioactive analog was achieved through optimized precursor synthesis and fluorination protocols. Comprehensive in vitro characterization encompassed: radiochemical purity and stability assessments, cellular uptake kinetics and inhibition assays in MCT-expressing BxPC3 (pancreatic) and 4T1 (breast) cancer models, biodistribution and dynamic micro-PET/CT imaging in tumor-bearing murine models. RESULTS: [F]FEtO-CHC, a CHC-derived radioligand, was synthesized via streamlined one-step radiosynthesis with 52.08 ± 6.74% decay-corrected yield (n=7), >99% radiochemical purity, and excellent stability. Cellular studies demonstrated MCTs-dependent uptake with significant suppression (>70%) by α-CHC competition. In vivo pharmacokinetics revealed favorable metabolic stability with dual hepatorenal clearance. Tumor uptake correlated with MCT expression levels, as confirmed by immunohistochemistry. CONCLUSIONS: This study establishes an efficient one-step radiosynthetic approach for [F]FEtO-CHC production and validates its specificity as a MCT-targeted PET probe, offering potential utility in tumor imaging with further structural optimization.
Long-term Local Control Following CEA-targeted Fluorescence-guided Surgery in Patients With Locally Advanced and Recurrent Rectal Cancer.
Warmerdam MI, Creemers DMJ, Kusters M … +10 more , Peeters KCMJ, Holman FA, Mieog JSD, Cailler F, Burger PJWA, Burggraaf J, Rutten HJT, Verhoef C, Vahrmeijer AL, Hilling DE
Mol Imaging Biol · 2025 Aug · PMID 40471424 · Full text
PURPOSE: In our previous phase 2 trial, patients with locally advanced (LARC) or locally recurrent rectal cancer (LRRC) received SGM-101, a CEA-targeted fluorescent agent, to enable real-time near-infrared fluorescence (...
PURPOSE: In our previous phase 2 trial, patients with locally advanced (LARC) or locally recurrent rectal cancer (LRRC) received SGM-101, a CEA-targeted fluorescent agent, to enable real-time near-infrared fluorescence (NIRF) guided surgery. This study demonstrated that SGM-101 enabled additional tumor removal in some patients and supported less invasive surgery in others. Despite this positive intraoperative effect, the impact on long-term tumor control is unknown. Therefore, in this article we report the long-term outcomes of all rectal cancer patients that participated to the trial. PROCEDURES: For all 29 LARC and LRRC patients that participated in the SGM-101 phase 2 trial, follow-up data were collected. Main outcome measure was 5-year local tumor control. RESULTS: The median follow-up of all patients was 5.0 years (IQR 4.5-5.5). Of the 12 LARC patients, three (25%) patients developed a local recurrence. The two patients in whom NIRF-guided surgery resulted in less invasive surgery remained locally recurrence-free. Among the 17 patients undergoing curative surgery for LRRC, 11 (65%) patients developed a local re-recurrence. Of the three patients who had an R0 instead of R1 as a direct result of SGM-101 guided surgery, one patient developed a local re-recurrence (33%), while the other two remained local recurrence-free. CONCLUSIONS: This is the first study to report follow-up data on patients undergoing tumor-targeted NIRF-guided surgery. Although SGM-101 resulted in warranted changes in surgical management intra-operatively, no improved long-term benefit could be observed for the entire cohort. However, the subset of patients whose surgical approach was modified based on NIRF - either by performing less invasive surgery or removing additional malignant tissue-showed favorable long-term outcomes. Results from ongoing large trials are awaited.
Evaluation of Lu-Labeled Lipiodol as a Targeted Radionuclide Therapy for Hepatocellular Carcinoma in a Preclinical Xenograft Model.
Kono Y, Utsunomiya K, Shiraishi T … +4 more , Kan N, Shiojima I, Maruyama K, Tanigawa N
Mol Imaging Biol · 2025 Aug · PMID 40465118 · Full text
BACKGROUND: Lutetium-177 (Lu) is a promising radionuclide for targeted cancer therapy due to its favorable theranostic properties. Transarterial lipiodol embolization is widely used for hepatocellular carcinoma (HCC), bu...
BACKGROUND: Lutetium-177 (Lu) is a promising radionuclide for targeted cancer therapy due to its favorable theranostic properties. Transarterial lipiodol embolization is widely used for hepatocellular carcinoma (HCC), but the potential of Lu emulsified into lipiodol (Lu-lipiodol) remains underexplored. This study aimed to evaluate the partition coefficient, biodistribution, and antitumor efficacy of Lu-lipiodol in a preclinical xenograft model. METHODS: After synthesizing Lu-oxine from Lu-chloride, the product was emulsified in lipiodol. Its radiochemical purity and partition coefficient were measured. F344 NJcl rnu/nu rats (n = 5) bearing bilateral thigh tumors (HC-4 cells) were randomized to receive Lu-lipiodol (2.8 MBq in 50 μL) or non-labeled lipiodol (50 μL) via surgical exposure and direct puncture of the right femoral artery. SPECT/CT images were acquired over 14 days, and biodistribution was confirmed by gamma counting at day 28. Tumor volumes and body weights were monitored to assess treatment response and toxicity. RESULTS: The Lu-lipiodol emulsion was obtained with a high radiochemical purity (> 99%). SPECT/CT showed high tumor accumulation (34.0% ± 4.4% immediately post-injection) that persisted up to day 28 (7.3% ± 1.2% of injected dose). Tumor growth was significantly suppressed with a treated-to-untreated volume ratio of 0.45 at day 14 (p = 0.017) and 0.59 at day 21 (p = 0.001). While off-target uptake was limited, moderate splenic accumulation (26.6% ± 17.5% ID) was noted. No marked body weight changes or gross organ abnormalities were observed. CONCLUSION: Lu-lipiodol for HCC therapy demonstrated effective tumor targeting and growth suppression of HCC in a preclinical xenograft model.
Go Fish! Hepatic Uptake of Clinical Hepatospecific Gadolinium-Based MRI Contrast Agents in Zebrafish is Similar to Humans.
Shapiro JA, Bhattacharyya T, Squire LA … +5 more , Mallett CL, Hix JM, Kenney LE, Aguirre A, Shapiro EM
Mol Imaging Biol · 2025 Aug · PMID 40461717 · Full text
PURPOSE: Zebrafish are a useful organism for investigating liver disease due to their genetic similarities with humans, particularly in genes associated with liver function. It has been posited that liver function can be...
PURPOSE: Zebrafish are a useful organism for investigating liver disease due to their genetic similarities with humans, particularly in genes associated with liver function. It has been posited that liver function can be assessed non-invasively by MRI, measuring the hepatic accumulation of gadolinium-based contrast agents (GBCAs). We characterized the hepatic uptake of various hepatospecific and non-hepatospecific clinical GBCAs in zebrafish. PROCEDURES: To introduce GBCAs systemically, zebrafish swam for 30 min in water containing 5 mM of various clinical hepatospecific or non-hepatospecific GBCAs. Fish were then sacrificed and underwent 3D, T1-weighted, high-resolution MRI at 9.4 T. In vitro MRI and transport studies of the same GBCAs were conducted in HEK293T cells transiently expressing OATP1D1, OATP1B2 and OATP1B3. RESULTS: T1-weighted ex-vivo MRI of zebrafish showed hyperintensity in the liver, gall bladder, bile ducts, and intestine for fish swimming in gadoxetate, but not for in gadobenate nor gadoterate. In vitro cell experiments confirm that gadoxetate but not gadobenate is efficiently transported by OATP1D1. CONCLUSION: Zebrafish liver accumulates gadoxetate but not gadobenate via OATP1D1 transport, among the two clinical hepatospecific MRI GBCAs, and also does not accumulate gadoterate, a non-hepatospecific GBCA. This pattern of GBCA hepatic uptake is similar to humans but differs from all other non-primates reported, which exhibit high hepatic uptake of both gadoxetate and gadobenate.
[Ga]Ga-PSMA-11 PET/CT and [F]Fluorocholine PET/CT in Assessment and Clinical Decision Making of Recurrent Prostate Cancer: A Prospective Crossover Trial.
Beheshti M, Shahbazi-Akbari M, Hacker M … +2 more , Loidl W, Langsteger W
Mol Imaging Biol · 2025 Aug · PMID 40437314 · Full text
PURPOSE: There are few prospective studies addressed toward the role of Gallium-labelled prostate-specific membrane antigen-11 ([Ga]Ga-PSMA-11) compared to [F]Fluorocholine ([F]FCH) PET/CT in clinical decision-making as...
PURPOSE: There are few prospective studies addressed toward the role of Gallium-labelled prostate-specific membrane antigen-11 ([Ga]Ga-PSMA-11) compared to [F]Fluorocholine ([F]FCH) PET/CT in clinical decision-making as prostate-specific PET-tracers. This study aims to evaluate the impact of PET/CT using [Ga]Ga-PSMA-11 and [F]FCH in clinical management of recurrent prostate cancer (PCa) and correlates imaging findings with clinical characteristics of PCa. PROCEDURES: Forty-six patients with PCa (mean age 68.3 ± 6.3 years) with biochemical recurrence were enrolled in this prospective crossover trial. All patients underwent both [Ga]Ga-PSMA-11 and [F]FCH PET/CT within a maximum interval of 12 days (median 7d). A standard randomization tool randomized the sequence of PET/CT imaging. Clinical decision-making occurred in an interdisciplinary meeting considering PET/CT findings. PET/CT-blinded readings were performed 3 months after imaging followed by a consensus meeting for final interpretation of detected lesions. RESULTS: Both imaging modalities detected 136 total malignant lesions. [Ga]Ga-PSMA-11 and [F]FCH PET/CT detected 125 and 60 lesions with a sensitivity of 96% and 48%, respectively. Tumor-to-background ratios and semi-quantitative PET parameters on [Ga]Ga-PSMA-11 were significantly higher in 54 (41.2%) tracer-avid congruent lesions detected on both imaging modalities. [Ga]Ga-PSMA-11 PET/CT exclusively detected 71 (52.2%) lesions, while 6 (4.4%) lesions were solely seen on [F]FCH PET/CT. [Ga]Ga-PSMA-11 and [F]FCH PET/CT were positive in 35/46 (76%) and 26/46 (57%) patients, respectively. PET/CT imaging led to a major treatment change in 4 (8.7%) patients, of which [F]FCH PET/CT had superior impact in one patient. CONCLUSIONS: [Ga]Ga-PSMA-11 PET/CT revealed superior diagnostic performance to [F]FCH PET/CT in patients with recurrent PCa, specifically with very low PSA levels ≤ 1 ng/ml. Moreover, it led to more accurate staging and clinical management of the disease. [F]FCH PET/CT may play a complementary role in rare, select high-risk cases with negative [Ga]Ga-PSMA-11 PET/CT and ongoing ADT.
Targeted Radionuclide Therapy Using a Lutetium-177 Labeled Human Anti-CD133 Antibody.
Wyszatko K, Janzen N, Law N … +7 more , Ventura M, Komal T, Savage N, Venugopal C, Kwiecien JM, Singh SK, Sadeghi S
Mol Imaging Biol · 2025 Aug · PMID 40405046 · Publisher ↗
PURPOSE: Targeted radionuclide therapy against cancer stem cell-specific markers, such as CD133, constitutes a promising strategy to eliminate resilient cancer stem cells for improved outcomes in refractory tumors. Here,...
PURPOSE: Targeted radionuclide therapy against cancer stem cell-specific markers, such as CD133, constitutes a promising strategy to eliminate resilient cancer stem cells for improved outcomes in refractory tumors. Here, we report the synthesis and evaluation of [Lu]Lu-DOTA-RW03, a CD133-targeted radioimmunotherapy. PROCEDURES: A fully human, anti-CD133 antibody (RW03) was conjugated with DOTA-NHS and radiolabeled with lutetium-177 to yield [Lu]Lu-DOTA-RW03. Radioligand binding assays on [Lu]Lu-DOTA-RW03 were performed using CD133 expressing HT-29 cells to determine binding affinity and immunoreactive fraction. Immunodeficient mice (n = 15) bearing HT-29 tumors were divided into 4 cohorts to establish the biodistribution of [Lu]Lu-DOTA-RW03 at 24, 48, and 96 h post-injection (n = 5 per cohort). Additional biodistribution and SPECT imaging studies were performed to establish tumor specificity and dose-dependent tumor uptake. In a dose-escalation therapy study, HT-29 tumor bearing mice (n = 20) were treated with either 4.0 ± 0.1, 9.6 ± 0.1, or 14.1 ± 0.2 MBq of [Lu]Lu-DOTA-RW03 or a vehicle control (n = 5 mice per cohort). Tumors from the therapy study were processed ex vivo for immunohistochemical and histopathological analysis. RESULTS: Radioimmunoconjugate [Lu]Lu-DOTA-RW03 (4.4 ± 0.1 DOTA per antibody) was isolated in 50 ± 10% radiochemical yield, 17-28 GBq/µmol molar activity, and in > 98% radiochemical purity. In vitro, the radiolabeled antibody exhibited excellent binding affinity (0.30 ± 0.03 nM) and > 75% immunoreactivity. The biodistribution of [Lu]Lu-DOTA-RW03 revealed notable tumor uptake (65 ± 5%ID/g, 96 h post-injection) and a favorable tumor-to-blood ratio (5:1, 96 h post-injection). In vivo antigen specificity was confirmed by a significant reduction (75%) in tumor uptake when [Lu]Lu-DOTA-RW03 was co-administered with a 200-fold molar excess of unlabeled RW03. The radioimmunoconjugate exhibited promising therapeutic efficacy in the treatment of CD133 expressing colorectal xenograft mouse model, with dose-dependent reductions in tumor growth rate and increased survival time. Histopathological and immunohistochemical analyses revealed elevated cell proliferation and extensive liquefactive necrosis at late stages into treatment, which provides an opportunity for multidosing and combination treatment strategies. CONCLUSIONS: These findings underscore the potential of [Lu]Lu-DOTA-RW03 as an effective therapy through targeting CD133 expressing cancer cells.
Visual and Quantitative F-FDG PET Tumor-liver Ratio in Radioiodine Refractory Differentiated Thyroid Cancer: Prognostic and Potential Predictive Value.
Li X, Liu H, Zhang S … +4 more , Zhang H, Zhang J, Qin S, Yu F
Mol Imaging Biol · 2025 Aug · PMID 40394424 · Publisher ↗
PURPOSE: The progression rate and course of radioiodine refractory differentiated thyroid cancer (RAIR-DTC) vary significantly, yet there lacks a precise method for predicting its progression. We hypothesized that using...
PURPOSE: The progression rate and course of radioiodine refractory differentiated thyroid cancer (RAIR-DTC) vary significantly, yet there lacks a precise method for predicting its progression. We hypothesized that using the liver as a reference organ can enable selective patient stratification. We aimed to establish fluorine-18 fluorodeoxyglucose positron emission tomography ([F] FDG-PET) tumor to-liver ratio (TLR score) to predict outcome for RAIR-DTC. PROCEDURES: This study included 64 patients with RAIR-DTC undergoing baseline F-FDG PET/CT. Patients were categorized by visual TLR (vTLR) into high (most lesions show higher uptake than the liver) or low (most lesions show lower uptake than the liver) groups using 3D maximum intensity projection (MIP) images. Quantitative TLR (qTLR) scores, including qTLR max (tumor SUVmax/liver SUVmax) and qTLRmean (tumor SUVmean/liver SUVmean), were semiautomatically derived from baseline PET, with high (≥ 1.5) and low (< 1.5) groups defined. Outcome data were progression-free survival (PFS). RESULTS: Among 64 patients, the distribution of high-TLR versus low-TLR groups varied across scoring methods: vTLR score allocated 36 (56.3%) high vs 28 (43.7%) low, qTLRmax score identified 29 (45.3%) high vs 35 (54.7%) low, and qTLRmean score demonstrated the most divergent pattern with 21 (32.8%) high vs 43 (67.2%) low. Agreement among qTLRmax, vTLR and qTLRmean score was moderate (Fleiss weighted k, 0.579). The median PFS of the high and low groups by vTLR score was 16.0, 29.0 months (P = 0.010) respectively, by qTLRmax score was 14.0, 27.0 months (P = 0.041), respectively, by qTLRmean score was 14.0, 28.0 months (P = 0.004), respectively. CONCLUSIONS: The TLR score was prognostic for PFS of RAIR-DTC. The vTLR score assessed on 3D MIP PET images yielded substantial reproducibility and combining qTLR score provided reliable prognostic value.
Radiogenomic Profiling for Survival Analysis in Gastric Cancer: Integrating CT Imaging, Gene Expression, and Clinical Data.
Nath AR, Thenmozhi K, Natarajan J
Mol Imaging Biol · 2025 Jun · PMID 40374970 · Publisher ↗
PURPOSE: This study aims to integrate CT (Computed Tomography) radiomic features, gene expression profiles, and clinical data to identify radiogenomic biomarkers and improve overall survival prediction in gastric cancer...
PURPOSE: This study aims to integrate CT (Computed Tomography) radiomic features, gene expression profiles, and clinical data to identify radiogenomic biomarkers and improve overall survival prediction in gastric cancer (GC) patients. PROCEDURES: Quantitative radiomic analysis was performed on 37 GC CT images, alongside gene expression and clinical data, to identify biomarkers associated with overall survival. Tumor segmentation and radiomic feature extraction were followed by Pearson correlation for feature selection. Gene Set Enrichment Analysis (GSEA) identified pathways linking gene expression changes with radiomic features. Regression models were applied to explore the relationships between these pathways, radiomic features, and clinical data in survival prediction. RESULTS: A total of 107 radiomic features were extracted, with 46 radiomic features, 1,032 genes, and one clinical feature (age) selected for further analysis. GSEA identified 29 significant KEGG pathways, mainly involving immune, signal transduction, and catabolism pathways. In survival analysis, the SVM model performed best, identifying age, genes CSF1R and CXCL12, and image features ShortRunHighGrayLevelEmphasis and Idn (Inverse Difference Normalized) as independent predictors. CONCLUSION: This study highlights the potential of integrating imaging, genomics, and clinical data for prognosis in GC patients, with identified genes suggesting new radiogenomic biomarker candidates for future evaluation.
Development of F-Labeled Deuterated Tropane Derivatives with High Metabolic Stability for PET Imaging of the Dopamine Transporter.
Hong J, Kang J, Zuo J … +4 more , Fang Y, Liu C, Li J, Chen Z
Mol Imaging Biol · 2025 Jun · PMID 40369387 · Publisher ↗
PURPOSE: Dopamine transporter (DAT) in the central nervous system is an attractive biomarker for the diagnosis and study of various neurodegenerative diseases. To develop in vivo metabolically stable positron emission to...
PURPOSE: Dopamine transporter (DAT) in the central nervous system is an attractive biomarker for the diagnosis and study of various neurodegenerative diseases. To develop in vivo metabolically stable positron emission tomography (PET) probes for DAT imaging with a high target/background ratio, two F-labeled tropane derivatives with deuteration on both the N-fluoropropyl and 2β-carbomethoxy groups of the tropane scaffold were synthesized and evaluated. METHODS: Radioligands [F]6 and [F]10 were synthesized from anhydroecgonine and radiolabeled with F through a "two-step one-pot" method. Lipophilicity, in vitro binding assay and microPET imaging in rats were performed. [F]10 showed a higher standardized uptake value ratio (SUVr) and was selected for further evaluations by in vivo metabolism and biodistribution. RESULTS: The radioligands [F]6 and [F]10 were obtained in radiochemical purities > 98% and molar activity of about 30 GBq/μmol. [F]6 or [F]10 demonstrated high specificity and binding affinity to DAT in vitro, with IC values between 2 ~ 3 nM. MicroPET imaging in wild type Sprague-Dawley rats revealed that [F]10 has a higher SUVr than [F]6. Blocking experiments demonstrated the selectivity and reversibility of [F]10 for DAT binding in microPET imaging. The diagnostic efficacy of [F]10 for DAT-related disorders was verified in semi-PD model rats with microPET. In vivo metabolic studies in rats indicated that [F]10 exhibited enhanced stability. Biodistribution experiments further confirmed that [F]10 accumulated in the DAT-rich region of the striatum. CONCLUSION: [F]10 is a highly promising metabolically stable F-labeled PET probe for DAT imaging, with potential clinical applications in detecting and monitoring DAT-related neurological disorders.
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