The pharmacokinetics of 68Ga-PSMA-11 leads to intense bladder accumulation, obscuring adjacent lesions. This study evaluated the feasibility of dynamic whole-body 68Ga-PSMA-11 PET/CT Patlak parametric imaging to reduce bladder signal interference, and compared the difference between the long axial field of view (LAFOV) PET/CT and short axial field of view (SAFOV) PET/CT. A total of 18 patients with prostate cancer were prospectively enrolled in this study, 9 patients were scanned on the uMI Panorama GS (FOV = 148 cm), and the other 9 patients were scanned on the uMI Panorama 35 C (FOV = 35 cm). The V images demonstrated a significant reduction in bladder TBR [LAFOV: TBR_SUV: 26.71 (14.50-34.83) vs. TBR_V: 0, P < 0.001; SAFOV: TBR_SUV: 14.56 (12.64–17.97) vs. TBR_V: 0.08 (0-1.42), P < 0.001] and SV [LAFOV: TBR_SUV: 154.06 ± 86.64 cm3 vs. SV_V: 0.94 ± 2.83 cm3, P < 0.001; SAFOV: SV_SUV: 174.33 ± 95.48 cm3 vs. SV_V: 12.90 ± 11.41 cm3, P < 0.001], achieving a 99.5
To evaluate the novel SPECT tracer 99mTc-CN7DG in a first-in-human clinical trial and assess its diagnostic value for central nervous system (CNS) tumors. Five Healthy volunteers were enrolled to assess the safety, biodistribution, and dosimetry of 99mTc-CN7DG. Subsequently, we prospectively enrolled 20 patients suspected a CNS tumor underwent MR, 18F-FDG PET/CT, and 99mTc-CN7DG quantitative SPECT/CT. The number of lesions and semi-quantitative parameters including the SUVmax, SUVmean, SUVmin, and lesion-to-background ratio (LBR) were measured. No adverse reactions were observed in any volunteers or patients after the injection of 99mTc-CN7DG. The mean whole-body effective dose estimated was 5.24 × 10⁻³ mSv/MBq. A total of 45 lesions were analyzed. Based on patient analysis, the detection rate was 90.0
Rationale: Current gastrointestinal endoscopy mainly depends on morphological changes for lesion diagnosis, thus often failing to detect early colorectal cancers (CRCs) with subtle morphological alterations. Optical molecular imaging via endoscopy may provide a unique means to identify early CRCs that precede the morphological changes observed via conventional endoscopy. In addition, optical imaging methods are utilized for intraoperative navigation when imaging tumors. However, the primary challenge in applying optical molecular imaging clinically is the restricted kinds of clinically endorsed targeted probes. Cerenkov luminescence (CL) can be observed with almost all clinically validated radiotracers. Therefore, Cerenkov luminescence imaging (CLI) does not require the development of new probes and can directly utilize clinically validated radiotracers. This study aimed to use Cerenkov luminescence endoscopy (CLE) for diagnosing early CRC effectively. Methods: In a prospective observational study, we use a self-produced CLE to diagnose colorectal lesions (mainly CRC). The CL images of the lesions were recorded and analyzed in comparison with PET/CT scans and histopathology. Results: A total of 20 colorectal lesions from 15 patients were included in the study. The agreement between CLE and PET/CT in diagnosing early CRC (stage Ⅰ CRC and advanced adenoma) was 100%. The level of agreement of CLE images with histopathology was 88.9% acceptable to high for early CRC. Compared with that of colorectal hyperplastic polyps, the signal-to-background ratio of CLE from early CRCs was significantly greater (1.33 ± 0.17 vs 0.99 ± 0.03, P < 0.001). In phantoms, tumor-bearing nude mice, and rectal pseudotumor model dogs, CLE detected CL at the corresponding lesion locations. Conclusions: This study demonstrated for the first time that CLE could utilize Cerenkov luminescence molecular imaging to diagnose early CRCs, overcoming the limitations of current endoscopic diagnosis based on morphological changes. (ClinicalTrials.gov, NCT05575765).
We examine whether glymphatic metrics play a mediating role between regional metabolic deficits and impaired consciousness. We find that compared to healthy controls, prolonged disorders of consciousness (pDoC) patients exhibited significant reduced blood oxygen level-dependent and cerebrospinal fluid signals (BOLD-CSF coupling), diffusion tensor imaging along the perivascular space (DTI-ALPS) index, and cerebral glucose metabolism, alongside a disrupted relationship between the two glymphatic metrics. Second, both BOLD-CSF coupling and DTI-ALPS index correlated positively with CRS-R scores (r = 0.317-0.450, p < 0.001). Cortical glucose metabolism was positively correlated with behavioral scores (r = 0.365-0.414, p<0.01), whereas subcortical glucose metabolism showed non-significant negative correlation (r=-0.018-0.159, p>0.05). Last, we reveal BOLD-CSF coupling preferentially associated with cortical metabolism, and DTI-ALPS preferentially linked to subcortical metabolism on consciousness. This two-pathway glymphatic-metabolic framework provides a novel integrative mechanism for understanding impaired consciousness.
Beyond its traditional role in oncology, PET/CT has significantly expanded the diagnostic landscape for infectious and inflammatory pathologies. This article systematically reviews recent progress in clinical research on PET/CT in these domains. Drawing upon relevant domestic and international clinical guidelines, the utility and constraints of PET/CT are evaluated across more than 20 specific conditions, including fever or inflammation of unknown origin, vascular graft infections, large-vessel vasculitis (LVV), and periprosthetic infections. Furthermore, significant strides have been made in developing highly specific molecular imaging probes that target bacterial metabolism, structural components, and the infection microenvironment, alongside their emerging clinical applications. Ultimately, this review aims to provide a comprehensive reference for clinicians to rationally utilize PET/CT as an adjunctive diagnostic and management tool.
Vascular endothelial growth factor receptor-3 (VEGFR-3) is overexpressed in tumor-induced lymphangiogenesis. TMVP1446/GS5 is a peptide analogue specifically targeting VEGFR-3, developed through substitution of the original peptide TMVP1446 with non-natural amino acids and terminal modification. This study aimed to evaluate the potential of 68Ga-labeled TMVP1446/GS5 as a probe for imaging primary tumors and metastatic lymph nodes. [68Ga]Ga-DOTA-TMVP1446/GS5 exhibited excellent labeling yield and radiochemical purity (RCP). Radio-HPLC analysis demonstrated comparable radiochemical and chemical stability to the original probe. Although stability in mouse plasma remained limited, [68Ga]Ga-DOTA-TMVP1446/GS5 exhibited modestly improved metabolic stability than the original probe. Cellular assays and surface plasmon resonance (SPR) analysis showed comparable or slightly higher binding affinity to VEGFR-3 relative to the original probe. In B16F10 subcutaneous xenografts, [68Ga]Ga-DOTA-TMVP1446/GS5 showed stronger and more sustained tumor uptake compared to the original probe, along with extended in vivo retention. At 2 h post-injection, tumor uptake reached 4.90 ± 0.36
Abstract Background 177Lu-PSMA-617 is a radioligand therapy targeting cells expressing prostate-specific membrane antigen (PSMA). The pharmacokinetics, dosimetry, and safety of 177Lu-PSMA-617 in participants with metastatic castration-resistant prostate cancer are described previously. In this study, we describe the blood pharmacokinetics behavior, biodistribution, and dosimetry of 177Lu-PSMA-617 to support its clinical use in Chinese participants. Results Nine participants were infused with 177Lu-PSMA-617 (range: 6985.6–8036.0 MBq). The geometric (Geo)-mean blood terminal half-life was 52.6 h, corresponding to an effective half-life of approximately 40 h. The Geo-mean maximum blood concentration of 11.3 ng/mL was achieved at a median time of 0.217 h post administration. The Geo-mean volume of distribution and clearance were 123 L and 1.62 L/h, respectively. The lacrimal glands received the highest absorbed dose of 3.1 mGy/MBq (Geo-coefficient of variation, 93.7%), followed by the thyroid, kidneys, and salivary glands. The Geo-mean whole-body effective dose was 890 mSv (Geo-coefficient of variation, 112.4%). Conclusions The blood pharmacokinetics and organ dosimetry of 177Lu-PSMA-617 in Chinese participants with progressive metastatic castration-resistant prostate cancer were consistent with those previously reported. The cumulative absorbed dose, corresponding to six cycles of treatment, was consistent with published literature. This analysis was conducted as part of a phase II study registered as NCT05670106 at ClinicalTrials.gov on November 7, 2022.
The impact of first-generation covalent KRASG12C inhibitors has been reduced due to the development of drug resistance, tolerability and challenges combining with immunotherapy. We designed olomorasib, a next-generation GDP-binding KRASG12C inhibitor, for nanomolar potency as well as selectivity over wild-type inhibition. In both in vitro and in vivo models of KRASG12C -mutant cancers, olomorasib reduces RAS activity and pERK levels, leading to substantial and significant tumor growth inhibition. Additionally, olomorasib combined with immune checkpoint inhibitors demonstrates greater anti-tumor activity compared to monotherapy. Furthermore, we demonstrate that olomorasib binds tightly to KRASG12C even in the presence of clinically relevant second site mutations, a known mechanism of resistance and limitation to currently approved KRASG12C inhibitors. These findings suggest that olomorasib could be effective for patients with KRASG12C mutant cancers either as monotherapy or in combination with immunotherapy. Olomorasib monotherapy and combination treatments are currently being investigated clinically.
MRI exhibits inherent limitations for preoperative TNM staging of rectal cancer, partially limiting its clinical utility. This head-to-head study compared the performance of ⁶⁸Ga-FAPI-04 PET/CT and MRI for stratified preoperative TNM staging of rectal cancer. We further assessed the predictive efficacy of quantitative PET/CT parameters for differentiating T stages, and explored whether these quantitative indicators could act as an adjunct to MRI staging. This single-center retrospective study recruited 81 patients diagnosed with rectal cancer, all of whom received whole-abdominal MRI and whole-body ⁶⁸Ga-FAPI-04 PET/CT scanning. Multiple quantitative metabolic parameters, including SUVmax, SUVmean, MTV, TLU, and TBR, were extracted for subsequent analyses. McNemar’s test was adopted to compare the sensitivity, specificity and diagnostic accuracy of the two imaging modalities in preoperative TN staging. Regarding M staging evaluation, the detection performance of metastatic lesions was only compared within the overlapping abdominopelvic scanning range of the two imaging protocols. All lesions located outside this overlapping coverage zone were merely described qualitatively without inter-group comparison. Spearman correlation analysis and binary logistic regression were applied to explore the correlations between T stage and the aforementioned quantitative parameters. ROC and DCA curves were plotted to quantify diagnostic performance and corresponding clinical net benefit, respectively. In T2-stage assessment, MRI demonstrated superior specificity and accuracy relative to PET/CT (85.25
The glymphatic system is essential for removing metabolic waste from the brain and facilitating the distribution of nutrients, but its status in patients with chronic disorders of consciousness (DoC) remains poorly understood. This study evaluated glymphatic function in chronic DoC and investigated its association with regional cerebral glucose metabolism. Forty-one patients with chronic DoC and 26 healthy controls (HCs) were retrospectively included. All participants underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI). Glymphatic function was quantified using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Standardized uptake value ratios (SUVRs) of key hubs within the 'mesocircuit model' were calculated using the cerebellum as reference. The characteristic glucose metabolic pattern (GMP) of chronic DoC was identified, and its expression scores were computed. Associations between the glymphatic function and cerebral glucose metabolism, behavioural score and serological markers were evaluated. Patients with chronic DoC showed significantly lower DTI-ALPS indices than HCs (P < 0.001). Within the patient group, moderate to strong correlations were observed between the DTI-ALPS index and the SUVRs of mesocircuit-associated regions, including the frontal cortex (r = 0.335, P = 0.002), parietal cortex (r = 0.383, P < 0.001), thalamus (r = 0.528, P < 0.001), brainstem (r = 0.665, P < 0.001), striatum (r = 0.537, P < 0.001) and globus pallidus (r = 0.372, P = 0.001), but not with the GMP score, behavioural score, or serological markers (all P > 0.05). Multivariate analysis further revealed that older age (β = -0.312, P < 0.001) and lower SUVRs in the parietal cortex (β = 0.196, P = 0.030) and brainstem (β = 0.482, P < 0.001) independently predicted reduced DTI-ALPS indices. This study provides in vivo evidence that glymphatic dysfunction is significantly associated with regional cerebral hypometabolism in chronic DoC, particularly in the parietal cortex and brainstem, which may serve as physiological drivers of CSF circulation.
[68Ga]Ga-PSMA-11 undergoes renal excretion, frequently leading to high levels of tracer activity in the bladder, which can mask nearby lesions. This study evaluated the feasibility of dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT Patlak parametric imaging to reduce bladder signal interference, thereby improving visualization. Eleven suspected prostate cancer patients underwent 60-minute dynamic PET/CT. SUV, Ki (Patlak slope), and V (Patlak intercept) parametric images were generated. Bladder-induced prostatic base obscuration was assessed via visual scoring (3-grade system). Signal-to-noise ratio (SNR) compared signal distributions in normal organs, lesions (primary, lymph node/bone metastases), and bladder. Correlations between Kimax, Vmax, and SUVmax were analyzed. V images significantly reduced bladder SNR (SNRV: 0.09 [0–0.89] vs. SNRSUV: 10.06 [7.95–12.14], p < 0.001) and signal volume (SVV: 10.93 ± 11.12 cm3 vs. SVSUV: 155.46 ± 95.18 cm3, p < 0.001), achieving a 93
This study developed and evaluated a positively charged CXCR4-targeted theranostic probe, 68Ga/161Tb-Pentikra, to enhance the affinity and therapeutic efficacy of the benchmark compound PentixaTher. The novel probe, modified with a d-Lys-d-Arg-d-Ala linker, demonstrated a 13-fold higher in vitro affinity for hCXCR4, as well as superior cellular retention. In CXCR4-expressing xenografted mice, 161Tb-Pentikra exhibited potent antitumor efficacy, reducing the mean tumor volume to 13.8% of the baseline. However, despite this enhanced in vitro and tumor-targeting performance, it conferred no survival benefit due to elevated off-target toxicity in the bone marrow and the digestive tract. Crucially, comparative biodistribution revealed significant species differences, with human models showing higher potential marrow exposure than mouse models. This study underscores a critical translational challenge: optimizing ligand affinity must be rigorously balanced against minimizing normal organ uptake to achieve therapeutic success in CXCR4-targeted radioligand therapy.
Deep image prior (DIP) has been proven to be an effective method to improve the image quality of positron emission tomography (PET) images when large datasets are not available. However most DIP-type methods are based on 3D U-net, which may be not suitable for unsupervised PET image denoising. In this work, we developed a neural architecture search method to find a better neural architecture for unsupervised PET image denoising. The cell level architecture and the network level architecture are searched alternatively. In each searching step, we designed a super network as a full set of all possible networks. Then the high-count PET images were used to update architecture and the low-count PET images were used to update weights. The performance of the searched architecture was evaluated through phantom study. The results showed that the searched neural architecture can better preserve image details while maintaining a lower noise level.
A 63-year-old woman presented with progressive facial edema. 18 F-FDG PET/CT showed a large soft tissue mass with heterogeneous hypermetabolism in the right atrium and superior vena cava, without distant metastases. The patient underwent surgical resection, and postoperative pathology confirmed a primary type B1 thymoma originating from the right atrium. To our knowledge, this case report details the 18 F-FDG PET/CT imaging features of primary intracardiac thymoma, which has rarely been described in the literature. It demonstrates the unique advantages of PET/CT in evaluating tumor malignant phenotype and systemic staging, and enriches the differential diagnosis spectrum of intracardiac hypermetabolic lesions.
A 74-year-old woman with a pulmonary nodule showing interval growth on follow-up imaging presented with dysphagia and abdominal bloating. 18F-FDG PET/CT displayed a gas-containing subcarinal soft-tissue density with intense FDG uptake and communicating with the adjacent hypermetabolic and focally thickened esophagus. These findings indicated a strong suspicion for esophageal malignancy complicated by fistula formation. Subsequent endoscopy demonstrated a nodular mucosal protrusion with a fistulous opening, revealing no evidence of malignancy. The patient received conservative treatment and clinical improvement. A coexisting left upper lobe ground-glass nodule with mild FDG uptake, unrelated to the esophageal lesion, was suggestive of early adenocarcinoma.
Background:Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) technique that enables quantitative assessment of prostate blood flow (PBF). Although the Prostate Imaging Reporting and Data System (PI-RADS) v2.1 is widely used for risk stratification of clinically significant prostate cancer (csPCa), whether combining ASL with the PI-RADS system can improve diagnostic accuracy remains to be explored. This study aimed to evaluate the risk of csPCa by integrating non-invasive ASL-derived PBF measurements with PI-RADS v2.1 scores in a clinical-imaging model. Methods:Of 233 patients with suspected prostate cancer (PCa) who underwent biparametric magnetic resonance imaging (bp-MRI) and ASL, 133 had pathologically confirmed benign or malignant lesions. The analysis included PBF measurements, PI-RADS v2.1 scores, and relevant clinical data from this cohort. This study employed both univariable and multivariable logistic regression to sequentially identify prognostic features. The diagnostic performance of PBF, PI-RADS v2.1 scores, and their combination in detecting csPCa was assessed using receiver operating characteristic (ROC) analysis. Bootstrap resampling was used for internal validation to ensure model stability. A nomogram was constructed to visualize the predictive model for csPCa risk, and decision curve analysis (DCA) was performed to evaluate its clinical utility. Results:Independent risk factors for csPCa included maximum prostate blood flow (PBF-max), PI-RADS v2.1 score, total prostate-specific antigen (tPSA), and prostate volume (PV). The diagnostic performance for csPCa, measured by the area under the curve (AUC), was 0.872 for PBF-max alone and 0.916 for the PI-RADS v2.1 score alone. Their combination significantly improved accuracy, yielding an AUC of 0.965. Furthermore, PI-RADS v2.1 scores demonstrated a strong positive correlation with PBF-max (r=0.62). Conclusions:The non-invasive quantification of PBF via ASL enhances the diagnostic capability of PI-RADS v2.1 scores for the detection of csPCa.