Molecular Imaging And Biology[JOURNAL]
Sun
200 papers
Direct Androgen Receptor Antagonism Enhances Therapeutic PSMA Radioligand Uptake in Prostate Cancer Models.
Hartrampf PE, Serfling SE, Hasenauer N … +4 more , Buck AK, Rogoll D, Kalogirou C, Weich A
Mol Imaging Biol · 2026 Jun · PMID 42324414 · Publisher ↗
BACKGROUND: Prostate-specific membrane antigen (PSMA) is a central target for prostate cancer theranostics. Androgen receptor (AR) signaling has been implicated in regulating PSMA expression; however, whether different m...
BACKGROUND: Prostate-specific membrane antigen (PSMA) is a central target for prostate cancer theranostics. Androgen receptor (AR) signaling has been implicated in regulating PSMA expression; however, whether different modes of AR pathway inhibition uniformly translate into enhanced functional radioligand uptake, particularly for therapeutic applications, remains incompletely defined. METHODS: AR-positive (LNCaP, C4-2) and AR-negative (PC3 PSMA +) prostate cancer models were investigated; parental PC3 cells served as PSMA-negative controls. Cells were treated with the direct AR antagonists enzalutamide and apalutamide or with the androgen biosynthesis inhibitor abiraterone. PSMA surface expression was quantified by flow cytometry. Functional uptake of [F]PSMA-1007 and [Lu]Lu-PSMA I&T was assessed by gamma counting. Glucose metabolism was evaluated using [F]FDG uptake, and PSA secretion was measured as a pharmacodynamic readout of AR pathway inhibition. RESULTS: Direct AR antagonism significantly increased PSMA surface expression in AR-positive models and translated into enhanced uptake of the therapeutic radioligand [Lu]Lu-PSMA I&T, with particularly pronounced effects in the castration-resistant C4-2 model. Diagnostic tracer uptake was also increased, though less consistently across models. In contrast, abiraterone did not induce consistent functional enhancement of radioligand accumulation despite PSMA upregulation in selected settings. AR-negative PC3 PSMA + cells exhibited stable baseline PSMA expression but showed no significant changes in PSMA levels or radioligand uptake following AR antagonist treatment. [F]FDG uptake was reduced under AR inhibition in AR-positive models, indicating that enhanced PSMA-targeted uptake was not driven by global metabolic activation. CONCLUSION: Direct AR antagonism enhances functional PSMA availability and increases short-term uptake of PSMA-targeted radioligands in AR-positive prostate cancer models. These findings provide mechanistic support for AR-mediated modulation of PSMA-targeted radioligand delivery and warrant further translational investigation.
Advances in PD-L1 Targeted Molecular Imaging Radiotracers Research: From Preclinical Exploration to Clinical Application.
Yu C, Liu Y, Chen H … +4 more , Tang R, Luo H, Chen X, Huang Z
Mol Imaging Biol · 2026 Jun · PMID 42315735 · Publisher ↗
Programmed death-ligand 1 (PD-L1) is highly expressed in tumour cells and the tumour microenvironment, mediates tumour immune evasion, and is a key target for cancer immunotherapy. Immunohistochemistry (IHC), as a conven...
Programmed death-ligand 1 (PD-L1) is highly expressed in tumour cells and the tumour microenvironment, mediates tumour immune evasion, and is a key target for cancer immunotherapy. Immunohistochemistry (IHC), as a conventional method for PD-L1 detection, has limitations such as invasiveness, temporal and spatial heterogeneity, and an inability to provide dynamic monitoring. In contrast, PD-L1-targeted molecular imaging enables non-invasive, quantitative, and whole-body visual assessment of PD-L1 expression, offering a precise tool for patient selection, treatment response prediction and dynamic monitoring in immunotherapy, and has thus become a focal point in precision oncology research. This paper systematically reviews the development trajectory of PD-L1-targeting radiotracers, including monoclonal antibodies, peptides, nanobodies, aptamers and small molecules. It summarises the targeting performance, pharmacokinetics, imaging efficacy and safety in preclinical and clinical studies; compares the advantages and suitable applications of different types of tracers; analyses the challenges currently facing the field, such as the lack of evaluation standards, tumour heterogeneity, insufficient clinical translation and a scarcity of multicentre data; and offers a prospect on the standardisation of PD-L1-targeted molecular imaging, the integration of diagnosis and treatment, multimodal imaging and its promotion and application in primary care settings. To date, more than 40 PD-L1-targeting tracers have undergone preclinical or clinical validation, with non-invasive imaging demonstrated to be feasible in over 100 cancer patients; early data support further in-depth research and clinical translation in this field.
Preclinical Evaluation of [F]JNJ-1: A Novel Positron Emission Tomography Ligand Targeting AMPAR/TARP γ8.
Xia CA, Zhang W, Berdyyeva T … +10 more , Huang C, Ameriks MK, Lebold TP, Maher MP, Constantinescu CC, Nguyen L, Wu N, Chen G, Kolb HC, Szardenings AK
Mol Imaging Biol · 2026 Jun · PMID 42298224 · Publisher ↗
PURPOSE: The AMPA receptor (AMPARs) mediates fast excitatory neurotransmission and is the central to synaptic plasticity, learning and memory dysregulation of this system has been implicated in epilepsy, neurodegeneratio...
PURPOSE: The AMPA receptor (AMPARs) mediates fast excitatory neurotransmission and is the central to synaptic plasticity, learning and memory dysregulation of this system has been implicated in epilepsy, neurodegeneration, and neuropsychiatric disorders. The transmembrane AMPA receptor regulatory protein γ8 (TARP γ8) plays a crucial role in the expression and localization of AMPARs within the brain, particularly in the hippocampus and cortex. A selective positron emission tomography (PET) ligand to image this target is of significant interest for investigating potential clinical AMPAR/TARP γ8 antagonists. This study describes the development and preclinical evaluation of a potent and selective tracer targeting TARP γ8, [F]JNJ-1. PROCEDURES: The binding potency of JNJ-1 was evaluated using a calcium flux assay in HEK-293 cells. The radiotracer was synthesized on an automated synthesizer via a one-step substitution. TARP γ8 target expression in brains was confirmed through immunohistochemistry (IHC), and adjacent brain sections were used for autoradiography (ARG). In vivo assays were conducted in rats, knockout mice, and non-human primates by [F]JNJ-1 PET imaging and JNJ-1 microdosing studies. RESULTS: JNJ-1 exhibited very high binding potency to TARP γ8, IC = 50 pM. Immunoreactivity of TARP γ8 showed high intensity in the hippocampus and moderate levels in the cortex across mouse, rat, and monkey brains. A microdosing with JNJ-1 study revealed high, moderate, and low levels of JNJ-1 uptake in the hippocampus, cortex, and cerebellum, respectively in wild-type mice (γ8 + / +), and low levels in all regions in knockout (γ8 - / -) mouse brains. In vitro ARG of [F]JNJ-1 corresponded with IHC staining on adjacent rat brain sections, and the signal being blocked by JNJ-2, a potent and selective antagonist of TARP γ8. In vivo PET imaging demonstrated high brain uptake in the expected areas in rats and monkeys, which was blockable by JNJ-2 in a dose-dependent manner. CONCLUSION: [F]JNJ-1 is emerging as a promising PET tracer with high in vitro binding affinity and evidence suggestive of target engagement at AMPAR/TARP γ8. The process of clinical validation is presently underway.
Probing Early Myocardial Remodeling in Response to a High-Fat Diet in Mice by Evaluation of Extracellular Volume Fraction Using 4D Retrospectively Gated Micro-CT Imaging.
Kwiatkowski G, Gąsiorek A, Ciastoń I … +3 more , Kozieł J, Velde GV, Chłopicki S
Mol Imaging Biol · 2026 Jun · PMID 42283978 · Publisher ↗
PURPOSE: The objective of this study was to evaluate whether retrospectively gated 4D micro-computed tomography (µCT) can quantify extracellular volume fraction (ECV) as an early marker of myocardial fibrosis and remodel...
PURPOSE: The objective of this study was to evaluate whether retrospectively gated 4D micro-computed tomography (µCT) can quantify extracellular volume fraction (ECV) as an early marker of myocardial fibrosis and remodeling in a high-fat diet (HFD) mouse model, and to determine its relationship with cardiac functional parameters. PROCEDURES: Male C57BL/6J mice were assigned to control diet or high-fat diet (HFD) groups, with HFD animals imaged after 8 or 16 weeks of feeding and control animals scanned at an age-matched time point. Contrast-enhanced 4D µCT with ECG gating was performed for cardiac function analysis and pre/post-contrast imaging for ECV quantification, corrected for hematocrit. Functional measures included left ventricular (LV) volumes, ejection fraction, mitral annular plane systolic excursion (MAPSE), circumferential shortening, and dobutamine stress response. RESULTS: Global LV ECV significantly increased at 8 weeks of HFD compared to controls, preceding changes in LV mass and ejection fraction. Early ECV elevation correlated with impaired lateral MAPSE, indicating subtle functional impairment despite preserved global systolic function. At 16 weeks, further remodeling was evident with increased LV mass, reduced epicardial circumferential shortening, decreased left atrial ejection area, and diminished dobutamine-induced contractile reserve. CONCLUSIONS: Retrospectively gated 4D µCT provides a robust and noninvasive method for early detection of diffuse myocardial fibrosis and functional impairment in small animal models. This approach enables longitudinal studies of cardiac disease progression and therapeutic interventions, offering translational value for preclinical cardiology research.
Molecular Imaging of Butyrylcholinesterase Associated with Amyloid-β Plaques Distinguishes 5XFAD from Wild-Type Mice: A Proof-of-Concept.
Reid GA, DeBay DR, Macdonald IR … +3 more , Laouz AB, Pottie IR, Darvesh S
Mol Imaging Biol · 2026 May · PMID 42209955 · Publisher ↗
PURPOSE: Diagnosis of Alzheimer's disease (AD) requires symptoms of dementia and accumulation of amyloid-β (Aβ) and tau in the brain. Molecular imaging of Aβ or tau in AD, though informative, is complicated by the findin...
PURPOSE: Diagnosis of Alzheimer's disease (AD) requires symptoms of dementia and accumulation of amyloid-β (Aβ) and tau in the brain. Molecular imaging of Aβ or tau in AD, though informative, is complicated by the finding that similar changes are found in brains of ~ 30% of cognitively normal older individuals. Butyrylcholinesterase (BChE), normally present in low levels in the cerebral cortex, is found in high levels associated with Aβ plaques in AD. When associated with plaques, the biochemical properties of BChE are altered. The aim of the present study was to determine if the BChE ligand, [F]1-methyl-4-piperidinyl p-fluorobenzoate ([F]BMP), can image BChE-associated plaques in the 5XFAD mouse model of AD and distinguish it from its wild-type (WT) counterpart. PROCEDURES: [F]BMP was synthesized and evaluated in wild-type (WT), 5XFAD and BChE knock-out (BChE-KO) mouse models for in vivo dynamic PET imaging of BChE. Time-activity curves were generated and [F]BMP clearance parameters were determined. Brain, liver and urine homogenates were evaluated for [F]BMP and its metabolites. Ex vivo autoradiography mapped the distribution of [F]BMP brain retention. RESULTS: In vivo PET imaging following injection of [F]BMP demonstrated significantly greater brain retention of activity in 5XFAD mice compared to WT, while BChE-KO mice appeared similar to WT levels. Metabolite analysis confirmed [F]BMP was metabolized in the periphery but survived in sufficient quantity to enter the brain. Ex vivo autoradiography showed [F]BMP retention in the 5XFAD brain where BChE-associated plaques were prominent. CONCLUSIONS: These results demonstrate that PET imaging of BChE-associated plaques is feasible, offering an avenue to evaluate the role(s) of BChE in AD pathogenesis and progression to complement the existing AD biomarker framework.
Brain Amyloid Deposition Is Negatively Associated with Cardiac Amyloid Retention in Apo E4 Carriers: A Pilot Study.
Pak K, Kim J, Kim K … +9 more , Kim K, Kim YJ, Lee H, Suh H, Moon E, Lee BD, Park JM, Choi JH, Lee YM
Mol Imaging Biol · 2026 May · PMID 42135537 · Publisher ↗
PURPOSE: We investigated the relationship between amyloid deposition in the brain and heart using positron emission tomography (PET) scan with a focus on the influence of the apolipoprotein (Apo) E4 genotype. PROCEDURE:...
PURPOSE: We investigated the relationship between amyloid deposition in the brain and heart using positron emission tomography (PET) scan with a focus on the influence of the apolipoprotein (Apo) E4 genotype. PROCEDURE: Twenty-eight participants (12 healthy controls, 11 patients with mild cognitive impairment, and 5 patients with Alzheimer's disease) were recruited. Each subject visited the institution three times on separate days for echocardiography, brain and cardiac F-Florbetaben PET, and brain magnetic resonance imaging. Myocardial tracer retention (MTR, %) was calculated as the change in the myocardial mean standardized uptake value on summed-frame images of the first 5 min and between 15 and 20 min. Brain amyloid deposition was quantified using the Centiloid scale. RESULTS: The mean MTR of all participants was 24.0%, with no significant difference between Apo E4 carriers and non-carriers. Within this pilot study, an inverse association was identified between MTR and brain amyloid deposition on the Centiloid scale specifically among Apo E4 carriers. In contrast, no significant association was found in Apo E4 non-carriers, consistent with the findings from the full-volume analysis. CONCLUSION: In this pilot study, an inverse association was observed between brain amyloid β deposition and cardiac amyloid retention in Apo E4 carriers, but not in non-carriers. These findings represent an exploratory clinical observation regarding potential genotype-specific patterns in central and peripheral amyloid dynamics. While the results are hypothesis-generating, they highlight the need for further research into the brain-heart axis in amyloid-related diseases, particularly in genetically at-risk individuals using larger confirmatory cohorts.
Recent Advances in the Development of CRISPR-Based Live-Cell Molecular Imaging and Sensing.
Hou M, Li Y, Wu X … +4 more , Long D, Sun D, Chen P, Huang H
Mol Imaging Biol · 2026 May · PMID 42128985 · Publisher ↗
Visualizing genome organization and transcriptional dynamics with spatial and temporal precision in living cells is essential for elucidating gene regulation and chromatin-associated disease mechanisms, yet conventional...
Visualizing genome organization and transcriptional dynamics with spatial and temporal precision in living cells is essential for elucidating gene regulation and chromatin-associated disease mechanisms, yet conventional methods confront a fundamental tension between endogenous-sequence targeting and live-cell compatibility. Operator-repressor systems require prior insertion of repetitive arrays at engineered loci, whereas fluorescence in situ hybridization mandates cell fixation and thereby precludes temporal analysis. CRISPR-Cas technologies, originally developed for genome editing, have been re-engineered into a versatile molecular-imaging toolkit capable of interrogating native sequences in living cells. Here, we systematically review CRISPR-based live-cell imaging and sensing platforms, critically evaluating their design principles, mechanistic foundations, and performance limitations. We examine dCas9-based DNA labeling, dCas12a systems for non-repetitive loci, Cas13- and Csm-mediated RNA imaging, novel fluorescent reporters, engineered ribonucleoproteins, and delivery innovations including reagent-based Oligo-LiveFISH. To organize this diverse literature, we distinguish three operationally distinct modalities-live-cell imaging, intracellular sensing, and diagnostic biosensing-and assess each platform through three unifying design trade-offs: sensitivity versus cellular perturbation, multiplexing capacity versus system complexity, and detection threshold versus biological fidelity. Building on this framework, we evaluate the integration of CRISPR imaging with super-resolution microscopy, artificial-intelligence-driven computational analysis, and multimodal spatial omics. Collectively, this synthesis clarifies current capabilities, delineates unresolved constraints, and charts a coherent path toward clinically relevant applications of CRISPR-based live-cell molecular imaging.
Evaluating the Effect of Sorafenib on Gd-EOB-DTPA-mediated Contrast Enhancement: An Experimental Study using DCE-MRI.
Chae YJ, Lee DW, Woo CW … +12 more , Sung YS, Choi JH, Tak E, Ha CH, Roh JK, Baek IJ, Pack CG, Heo H, Kim KW, Kim JK, Choi Y, Woo DC
Mol Imaging Biol · 2026 May · PMID 42128984 · Publisher ↗
PURPOSE: Despite the potential impact of sorafenib on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-mediated contrast enhancements, attempts to assess these effects are rare. This study aimed...
PURPOSE: Despite the potential impact of sorafenib on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-mediated contrast enhancements, attempts to assess these effects are rare. This study aimed to investigate the interaction between Sorafenib and Gd-EOB-DTPA by quantifying the T1 and T2 relaxation times and the relative enhancement rates (RERs) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the liver. PROCEDURES: The effects on contrast enhancement were assessed using MRI with Chang liver cells and SD rats. MR phantom images were obtained after treating cells with varying dosages of Gd-EOB-DTPA (5, 10 mM) and sorafenib (10, 30 μM) to evaluate MR relaxivities. For the animal study, DCE-MRI was performed following intravenous administration of 25 µmol/kg Gd-EOB-DTPA and two different doses of sorafenib (10, 30 mg/kg). RER was analyzed to evaluate sorafenib's effects on Gd-EOB-DTPA uptake in the liver. RESULTS: Phantom experiments demonstrated alterations in T1 and T2 values, with a tendency towards shortening disrupted by the addition of sorafenib to Gd-EOB-DTPA-treated Chang liver cells. The RERs of DCE-MRI in the liver exhibited a dose-dependent decrease following sorafenib administration, with recovery observed after 4 h. CONCLUSIONS: Our results provide quantitative information on sorafenib-mediated interference with Gd-EOB-DTPA-induced contrast enhancement and offer experimental evidence suggesting the possibility of drug-drug interactions between sorafenib and Gd-EOB-DTPA. Although further research is needed to fully elucidate the impact of these interactions, caution is warranted when using these two agents concurrently for liver MRI.
Clinical Effectiveness of miR-760 to Distinguish Benign and Malignant Pulmonary Nodules on the Basis of Low-Dose Spiral CT Imaging.
Chen J, Li F, Chen J … +3 more , Li Q, Ren Y, Liu R
Mol Imaging Biol · 2026 May · PMID 42104044 · Publisher ↗
BACKGROUND: The differential diagnosis of benign and malignant pulmonary nodules is a key problem in clinical diagnosis. Low-dose spiral CT (LDCT) is a commonly used screening method, but it has the limitations of insuff...
BACKGROUND: The differential diagnosis of benign and malignant pulmonary nodules is a key problem in clinical diagnosis. Low-dose spiral CT (LDCT) is a commonly used screening method, but it has the limitations of insufficient specificity. There is an urgent need for molecular markers to assist diagnosis. METHODS: A total of 240 patients with pulmonary nodules were enrolled in this study. The expression of serum miR-760 was detected by polymerase chain reaction (PCR). Receiver operating curve (ROC) was used to evaluate the potential of miR-760 in the diagnosis of lung cancer, and logistic regression analysis was used to evaluate its significance in the risk assessment of lung cancer. Target genes were screened by bioinformatics, protein-protein interaction (PPI) network was constructed, and hub genes were screened. RESULTS: The expression of miR-760 in the lung cancer group was significantly lower than that in the benign group (P < 0.001). Its AUC for differentiating benign and malignant was 0.867. When LDCT combined with miR-760, the area under the curve (AUC) increased to 0.955. Logistic regression analysis showed that miR-760 was a risk factor for lung cancer incidence. PPI network analysis screened 10 hub genes (HMGCR, INSR, CDK6, etc.), which were enriched in cancer related pathways such as HIF-1 and actin cytoskeleton. CONCLUSIONS: miR-760 combined with LDCT can significantly improve the differentiation ability of benign and malignant pulmonary nodules, and its mechanism may activate tumor-related signaling pathways by targeting the core genes of PPI network. This study provides a new combination of molecular markers and mechanistic clues for the accurate diagnosis of pulmonary nodules.
Diagnostic Performance of Somatostatin Receptor-directed PET/CT for Tumor-induced Osteomalacia.
Heinrich M, Kosmala A, Dierks A … +9 more , Genest F, Gerhard-Hartmann E, Haug L, Achtziger S, Raab P, Buck AK, Lapa C, Michalski K, Seefried L
Mol Imaging Biol · 2026 May · PMID 42082869 · Publisher ↗
AIM: To evaluate the efficacy of somatostatin receptor (SSTR)-directed PET/CT in localizing phosphaturic mesenchymal tumors (PMT) in patients with suspected tumor-induced osteomalacia (TIO) and to explore relationships b...
AIM: To evaluate the efficacy of somatostatin receptor (SSTR)-directed PET/CT in localizing phosphaturic mesenchymal tumors (PMT) in patients with suspected tumor-induced osteomalacia (TIO) and to explore relationships between imaging parameters and biochemical markers. METHODS: This retrospective analysis included 20 patients with suspected TIO, undergoing SSTR-directed PET/CT. Imaging findings and laboratory markers were assessed. SSTR-positive tumors were resected, while patients without detectable tumor, but persistent renal phosphate wasting, continued on medical treatment. Follow-up assessments included laboratory values and clinical examinations. RESULTS: PMT were detected on PET in 12 patients (60%), were resected, and confirmed immunohistochemically. Phosphorus levels (r = 0.26; p = 0.03), tubular reabsorption of phosphate (TRP; r = 0.77; p < 0.01) and tubular maximum of phosphate reabsorption over GFR (TmP/GFR; r = 0.44; p = 0.07) were lower in patients with detected PMT compared to those without. Elevation of fibroblast growth factor 23 (FGF23) was not significantly higher in PMT positive vs negative patients (253% vs 134% above the upper limit of normal; p = 0.97). Total lesion uptake (TLU) negatively correlated with TmP/GFR (r = -0.71; p = 0.03). A maximum standardized uptake value (SUVmax) threshold of 7.6 differentiated PMT from bone fractures (83% sensitivity; 100% specificity). Post-resection follow-up confirmed clinical cure in all cases. CONCLUSION: In SSTR-directed PET/CT, a distinction between PMT and bone fracture may be possible with a SUVmax threshold of 7.6. The integration of PET derived TLU, along with TmP/GFR may improve diagnosis and treatment planning for TIO.
Transporter-Mediated Hepatic Uptake of EOB-DTPA and BOPTA Is Largely Independent of Chelated Metal.
Kenney LE, Mallett CL, Hix JM … +2 more , Bhattacharyya T, Shapiro EM
Mol Imaging Biol · 2026 May · PMID 42082868 · Publisher ↗
PURPOSE: Metal chelates play a crucial role in diagnostic imaging and radiotherapy. While gadolinium-based chelates are widely used in MRI, radiometal chelates are increasingly used in nuclear medicine and theranostics....
PURPOSE: Metal chelates play a crucial role in diagnostic imaging and radiotherapy. While gadolinium-based chelates are widely used in MRI, radiometal chelates are increasingly used in nuclear medicine and theranostics. Despite their clinical importance, the extent to which the identity of the coordinated metal influences in vivo chelate pharmacology remains unclear. The goal of this work was to determine whether metal substitution alters transporter-mediated cellular uptake and pharmacological behavior of hepatospecific chelates. PROCEDURES: Apo-forms of the clinical hepatospecific MRI contrast agents EOB-DTPA and BOPTA were generated and re-chelated with eight different metals (Sc, Y, Pr, Eu, Gd, Tb, Dy, Ho). In vitro transport of these chelates was assessed in cells expressing rodent and human hepatic transporters. In vivo hepatic uptake was evaluated in mice expressing either wild-type or human hepatic transporters. Tissue distribution and clearance were quantified analytically. RESULTS: In vitro uptake of EOB-DTPA and BOPTA chelates by cells expressing rodent and human transporters showed no statistically significant differences across metals. In vivo studies in mice similarly showed no statistically significant differences in hepatic uptake across metals, with the exception of reduced uptake observed for Sc-EOB-DTPA in wild-type animals. No evidence of free metal accumulation in soft tissue was detected. Chelate clearance via renal and hepatobiliary pathways was similar across metals. CONCLUSIONS: Within the class of trivalent metals examined and for EOB-DTPA and BOPTA chelates, transporter-mediated uptake, biodistribution, and clearance were largely independent of metal identity under the conditions tested. These findings support the use of common chelate scaffolds across multiple metals, while highlighting the importance of ligand structure and transporter interactions in governing pharmacology.
Dual Quantification of Skeletal Muscle Perfusion and Metabolism in a Porcine Model of Peripheral Artery Disease Using Multiparametric F-FDG PET Imaging.
Chou TH, Nabavinia M, Rimmerman ET … +4 more , Mansfield C, Musini KN, Tram NK, Stacy MR
Mol Imaging Biol · 2026 May · PMID 42067735 · Publisher ↗
BACKGROUND: A standard imaging strategy for quantifying skeletal muscle perfusion in peripheral artery disease (PAD) does not exist, and the widespread use of PET imaging for this purpose has traditionally been limited b...
BACKGROUND: A standard imaging strategy for quantifying skeletal muscle perfusion in peripheral artery disease (PAD) does not exist, and the widespread use of PET imaging for this purpose has traditionally been limited by the need for onsite production of short half-life perfusion radioisotopes. Therefore, this study investigated the feasibility of multiparametric PET imaging with commercially available fluorine-18 (F)-fluorodeoxyglucose (FDG) for the quantification of skeletal muscle perfusion and metabolism in a porcine model of PAD. METHODS: Eight Yorkshire pigs underwent 60-min dynamic F-FDG PET imaging under resting conditions immediately following unilateral surgical ligation of the femoral artery and 2 weeks after arterial occlusion. Calf muscle perfusion was computed using 1-compartment modeling of the first 2.5 min of PET data acquisition, and the metabolic rate of glucose (MRGlu) was computed using 3-compartment modeling of the entire 60-min dataset. Two weeks after arterial occlusion, the gastrocnemius muscle was harvested to compare microvascular density between ischemic and control hindlimbs. RESULTS: Calf perfusion and MRGlu were significantly reduced following peripheral artery occlusion and recovered to control levels 2 weeks later. Recovery of perfusion and metabolism in calf skeletal muscle coincided with a significant increase in calf muscle capillary density 2 weeks after arterial occlusion. CONCLUSIONS: This study demonstrates the novel use of dynamic, multiparametric F-FDG PET/CT imaging for quantifying ischemia-induced alterations in skeletal muscle perfusion and metabolism, providing a unique comprehensive approach for evaluating PAD pathophysiology and creating opportunities for monitoring treatment responses to emerging therapeutics.
Estimation and Correction of the Partial Volume Effect Using Personalized Phantoms of Lymph Node Metastases in Lutetium 177 SPECT/CT Dosimetry.
Hinz JR, Kuwert T, Beck M … +2 more , Ritt P, Grings A
Mol Imaging Biol · 2026 Apr · PMID 42053713 · Publisher ↗
PURPOSE: This study aims to quantify and to correct for partial volume effect (PVE) in lymph node metastases of prostate cancer (PC) on Lu-177 SPECT images using 3D-printed phantoms of these structures to establish a gro...
PURPOSE: This study aims to quantify and to correct for partial volume effect (PVE) in lymph node metastases of prostate cancer (PC) on Lu-177 SPECT images using 3D-printed phantoms of these structures to establish a ground truth. PROCEDURES: Ten individuals with clearly delineated, SPECT-positive lymph node metastases were retrospectively selected from a cohort of PC patients undergoing radioligand therapy (RLT). Manual segmentation of the metastases was performed on the CT component. The segmented lymph nodes were 3D-printed as patient-specific lymph node phantoms with volumes ranging from 0.18 to 23.7 ml using a high-resolution 3D printer. These phantoms were filled with Lu-177 and analyzed in a SPECT/CT system to quantify PVE. An exponential curve fit of the recovery coefficient (RC) versus the surface-area to volume ratio (SA:V) was derived from the spheres of a NEMA ICE body phantom and used to correct for PVE in the lymph node phantoms. This method was compared with other post-reconstruction partial volume corrections (PVC). RESULTS: For a tumor to background ratio (TBR) of 10:1 the RCs varied widely, from 82% to 10.4% depending on phantom size. Using the NEMA IEC body phantom, an exponential correlation was established between SA:V and RC, with R values exceeding 0.97 across measurements at four different TBRs. Using this curve for PVE correction, the RCs of the lymph node phantoms had an average deviation from the ground truth of 1.15 ± 10.15% (average ± standard error of the mean). This method had a higher accuracy than the other PVCs studied. CONCLUSIONS: The low RCs obtained for lymph node metastases suggest that Lu-177-dosimetry is in these structures grossly inaccurate without PVE correction. Applying the SA:V/RC curve established using the NEMA IEC body phantom for this purpose reduces PVE-related errors considerably.
Quantitative [F]PSMA-1007 PET in Treatment Response Monitoring of Brain Metastases from Non-small Cell Lung Cancer.
Lysvik EK, Tulipan AJ, Haakensen VD … +3 more , Revheim MR, Emblem KE, Hjørnevik T
Mol Imaging Biol · 2026 Apr · PMID 42026421 · Publisher ↗
PURPOSE: Prostate-specific membrane antigen (PSMA) is expressed in several solid tumours, including brain metastases (BMs) from lung cancer. We investigated quantitative [F]PSMA-1007 uptake and treatment response in BMs...
PURPOSE: Prostate-specific membrane antigen (PSMA) is expressed in several solid tumours, including brain metastases (BMs) from lung cancer. We investigated quantitative [F]PSMA-1007 uptake and treatment response in BMs of patients with non-small cell lung cancer (NSCLC). PROCEDURES: Eleven patients with BM of NSCLC underwent 95-min dual-time-point dynamic [F]PSMA-1007 PET/CT and a whole-body static scan before and after stereotactic radiosurgery (SRS) with a median dose of 20 Gy (range: 8-25 Gy) given in a median of 1 fraction (range: 1-3). Seven patients completed both exams. Image-derived input functions were extracted from the internal carotid arteries, and pharmacokinetic analysis using Patlak modelling yielded the influx constant (K). Standardised uptake value (SUV), biological tumour volume (BTV) and tumour heterogeneity using the coefficient of variance (CoV) were assessed. RESULTS: [F]PSMA-1007 PET showed uptake in the first exam in BMs and primary lung tumour in all patients. Significant inter-patient and intra-lesion heterogeneity in tracer uptake was observed in BMs with median Ki of 0.005 ml/ccm/min (range: 0.003-0.018 ml/ccm/min), SUV of 4.2 g/ml (range: 0.4-34.4 g/ml), CoV of 0.36 (range 0.06-0.85) and BTV of 2.35 ml (range 0.03-22.29 ml). After SRS, reductions in K (37%), SUV (50%), CoV (24%) and BTV (71%) were noted. Median SUV in the lungs were 6.1 g/ml (range: 3.2-13.6 g/ml) at the initial exam and 6.3 g/ml (range: 3.8-11.8 g/ml) at the second exam. CONCLUSION: [F]PSMA-1007 PET is a promising diagnostic tool for BMs from NSCLC. The uptake and heterogeneity, along with the marked reduction post-therapy, highlights its potential for monitoring treatment response. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03951142. Registered 5 October 2019, https://clinicaltrials.gov/ct2/show/NCT03951142 . EudraCT no 2018-003229-27. Registered 26 February 2019, https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-003229-27/NO .
2025 World Molecular Imaging Congress Program.
Mol Imaging Biol · 2026 Feb · PMID 42010232 · Publisher ↗
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Accurate Reference Region Calculation in Mouse Brain [F]fallypride Studies.
Miranda A, Elvas F, Staelens S
Mol Imaging Biol · 2026 Apr · PMID 42010231 · Publisher ↗
Quantification of the dopamine D receptors tracer [F]fallypride is usually performed by defining the cerebellum (CB) as the reference region for its use in kinetic modeling. In mouse studies, [F]fallypride is defluorinat...
Quantification of the dopamine D receptors tracer [F]fallypride is usually performed by defining the cerebellum (CB) as the reference region for its use in kinetic modeling. In mouse studies, [F]fallypride is defluorinated causing gradual uptake in the skull which, in addition to extra-striatal binding, can contaminate the CB activity, therefore introducing errors in reference region kinetic modeling. Here we propose a method using non-negative matrix factorization (NMF) to accurately extract the reference region time activity curve (TAC) unaffected by spill-over from surrounding regions. We compared the NMF method with template-based CB reference region (erodedCB), where the region was eroded to avoid spill-over. The different methods were applied in a drug challenge study using RX821002, and compared with results obtained using [C]raclopride. Striatal and brain parametric maps of nondisplaceable binding potential (BP) were calculated with the different methods, and differences between baseline and challenge were investigated. The NMF reference region TACs showed higher peak and lower tail activity compared with erodedCB. Striatal BP values calculated with NMF were about 20% higher compared to those calculated with erodedCB, and difference between baseline and challenge increased using NMF (NMF: 11.5%, erodedCB: 7.0%). Parametric t-statistic maps show clusters with significant differences using NMF but not with erodedCB. [C]raclopride BP differences between baseline and challenge were lower (6.1%) than with [F]fallypride, but BP variability was lower. In summary, NMF allowed us to extract reference region TACs without contamination from skull or extra-striatal uptake, which improved voxel-wise detection of differences in a drug challenge study.
Prospective Pilot Study of C-acetate and F-FDG with PET/CT and PET/MRI for Lesion Detection in Multiple Myeloma.
Yancey K, Han W, Yang M … +15 more , Nguyen BD, Zhang N, Graf K, Shim KG, Wiedmeier-Nutor EE, Yadav U, Stewart K, Chhabra S, Bergsagel L, Koran ME, Martinez F, Huang S, Roarke M, Fonseca R, Shin CH
Mol Imaging Biol · 2026 Apr · PMID 41989739 · Publisher ↗
PURPOSE: To compare the diagnostic performance of C-acetate and F-FDG across hybrid PET/CT and PET/MRI platforms in patients with multiple myeloma (MM). METHODS: In this prospective pilot study, seven patients with MM un...
PURPOSE: To compare the diagnostic performance of C-acetate and F-FDG across hybrid PET/CT and PET/MRI platforms in patients with multiple myeloma (MM). METHODS: In this prospective pilot study, seven patients with MM underwent repeated-measures imaging with F-FDG PET/CT, F-FDG PET/MRI, C-acetate PET/CT, and C-acetate PET/MRI. In addition to lesion quantification, the lesions were visually scored for conspicuity. No functional sequences or contrast-enhancement was used in the MRI protocol. RESULTS: C-acetate detected a greater number of lesions and demonstrated higher visual conspicuity than F-FDG across both PET/CT and PET/MRI platforms. CONCLUSION: C-acetate PET imaging may offer improved lesion detection compared to F-FDG in MM. Although the advantage of PET/MRI was not observed over PET/CT in this context, further studies incorporating additional MRI sequences and larger cohorts are warranted.
An Optimized Fast Track Protocol to Enhance the Image Quality of 18F-FDG PET Myocardial Viability Imaging in Diabetic CAD Patients: A Randomized Controlled Trial.
Mandal A, Taywade S, R L V … +3 more , Majeed A, Taywade O, Kumar R
Mol Imaging Biol · 2026 Apr · PMID 41981248 · Publisher ↗
BACKGROUND: Standard ASNC guidelines for 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) myocardial viability imaging often yield suboptimal image quality in patients with diabetes mellitus, primarily d...
BACKGROUND: Standard ASNC guidelines for 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) myocardial viability imaging often yield suboptimal image quality in patients with diabetes mellitus, primarily due to altered glucose-insulin kinetics. This study evaluated an optimized fast-track (OFT) patient preparation protocol designed to improve image quality and reduce preparation time in diabetic patients with coronary artery disease (CAD). METHODS: We conducted a prospective, randomized controlled trial involving 50 diabetic patients with known CAD. Patients were stratified based on diabetes duration, fasting blood sugar (FBS), and HbA1C levels, then assigned to either a standard preparation group or the OFT protocol group prior to undergoing 18F-FDG PET imaging. Image quality was assessed qualitatively using a visual grading scale and semi-quantitatively using the myocardium-to-blood pool (M/B) standardized uptake value ratio. Patient preparation time (PPT) was measured from oral glucose administration to 18F-FDG injection. RESULTS: The OFT group demonstrated a higher proportion of interpretable scans (92% vs 64%; p = 0.017) and significantly greater M/B ratios (mean ± SD: 12.44 ± 5.37 vs 7.23 ± 3.42; p < 0.001) compared to the standard group. Median PPT was also significantly shorter in the OFT group (82 min) than in the standard group (95 min; p = 0.003). CONCLUSIONS: The optimized fast-track protocol significantly improves image quality and reduces patient preparation time in diabetic individuals undergoing 18F-FDG PET myocardial viability imaging. This protocol offers a practical and effective alternative to the standard ASNC approach, with potential for integration into routine clinical practice.
In Vivo Tracking Modalities for Oncolytic Reovirus: Principles, Clinical Applications, and Translational Integration.
Rastegarpanah M, Kafi ZZ, Negahdari B
Mol Imaging Biol · 2026 Apr · PMID 41963749 · Publisher ↗
OBJECTIVES: Oncolytic reovirus, particularly Pelareorep, is a promising cancer therapeutic due to selective replication in Ras-activated tumor cells and immunomodulatory effects. This review aims to critically evaluate c...
OBJECTIVES: Oncolytic reovirus, particularly Pelareorep, is a promising cancer therapeutic due to selective replication in Ras-activated tumor cells and immunomodulatory effects. This review aims to critically evaluate current and emerging in vivo tracking strategies, emphasizing translational relevance and clinical implementation. EVIDENCE ACQUISITION: We systematically analyzed preclinical and clinical studies employing optical imaging, nuclear imaging, magnetic resonance imaging, ultrasound/photoacoustic techniques, molecular reporters, and nanoparticle-based platforms. Special focus was placed on integrating functional imaging and molecular assays in Pelareorep trials to monitor viral distribution and therapeutic response. RESULTS: Optical imaging offers high sensitivity for preclinical investigations; however, it is limited by shallow tissue penetration. Nuclear imaging provides quantitative, whole-body monitoring that is suitable for clinical translation, whereas MRI and ultrasound/photoacoustic modalities enable real-time visualization of both structural and functional aspects. Nanotechnology-based platforms facilitate multimodal imaging and targeted delivery, while molecular tools such as reporter genes, CRISPR-driven circuits, and viral barcoding further enhance spatiotemporal resolution. Clinical trials with Pelareorep demonstrate the feasibility of integrating imaging with molecular assays to evaluate safety, delivery efficiency, and antitumor activity. Persisting challenges include limited genome capacity, immune-mediated clearance, and suboptimal signal penetration. CONCLUSION: Emerging strategies, including synthetic biology reporters, AI-driven image analysis, biosensors, and liquid biopsies, provide scalable, patient-specific tracking solutions. This integrative framework bridges preclinical insights with clinical translation, supporting optimized design, monitoring, and personalization of oncolytic reovirus therapy.
Comparison of [F]DPA-814 with [F]DPA-714 for TSPO Imaging in an Experimental Model.
van der Bie J, Bakker J, Verschoor EJ … +8 more , Nutma E, Middeldorp J, Beaino W, Kassiou M, Danon JJ, Langermans JAM, Windhorst AD, Stammes MA
Mol Imaging Biol · 2026 Apr · PMID 41922885 · Publisher ↗
PURPOSE: [F]DPA-714 is a valuable tracer for studying (neuro)inflammation, with well-characterized tracer kinetics and an established imaging window. However, its clinical utility is restricted by the TSPO polymorphism (...
PURPOSE: [F]DPA-714 is a valuable tracer for studying (neuro)inflammation, with well-characterized tracer kinetics and an established imaging window. However, its clinical utility is restricted by the TSPO polymorphism (rs6971), which influences binding affinity in humans. The newly developed tracer [F]DPA-814 overcomes this limitation and has shown promising results in a preclinical rat model. To further assess its clinical potential, we compared [F]DPA-814 to [F]DPA-714 for inflammation imaging in SARS-CoV-2-infected macaques in a longitudinal setting. PROCEDURES: Dynamic positron emission tomography (PET) imaging was conducted in four healthy macaques to identify the optimal imaging window for [F]DPA-814. Four additional macaques were infected with SARS-CoV-2 and monitored for 12 months using whole-body PET-computed tomography (CT) with both tracers. Baseline scans were compared to PET-CTs obtained at 4, 9 and 16 days and at 6 and 12 months post-infection, covering the head, thorax and abdomen. Tracer uptake was assessed in several organs. RESULTS: At baseline, [F]DPA-814 showed higher lung uptake with minimal washout compared to [F]DPA-714. Although lung lesions developed after infection, [F]DPA-814 did not demonstrate lesion-specific uptake, unlike [F]DPA-714. In the brain, the tracers also displayed divergent uptake patterns despite comparable TSPO levels across animals and regions. CONCLUSIONS: [F]DPA-814 exhibits a distinct whole-body distribution, particularly in the lungs and brain, in both naïve and SARS-CoV-2-infected macaques compared with [F]DPA-714, likely reflecting differences in tracer kinetics. Based on these data, [F]DPA-814 may not fully replace [F]DPA-714 for lung and brain imaging, and further studies are required to evaluate its suitability in other anatomical regions.
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