American journal of nuclear medicine and molecular imaging最新文献

Observational studies suggest a link between osteoarthritis (OA) and frailty, but the shared genetic architecture and causal relationships remain unclear. We analyzed X-ray and ¹⁸F-FDG PET/CT images in frail and non-frail individuals and conducted genetic correlation analyses using Linkage Disequilibrium Score Regression (LDSC) based on recent Genome-Wide Association Studies (GWAS) for OA and frailty. We identified pleiotropic single-nucleotide polymorphisms (SNPs) through Cross-Phenotype Association (CPASSOC) and Colocalization (COLOC) analyses and investigated genetic overlaps using Multi-marker Analysis of GenoMic Annotation (MAGMA). Transcriptome-wide association studies (TWAS) were conducted to analyze pleiotropic gene expression, and Mendelian Randomization (MR) was used to assess causal relationships between OA and frailty. Frail individuals showed more severe OA on X-ray (67% vs. 31%, P ≤ 0.01) and higher SUVmax on ¹⁸F-FDG PET/CT (4.1 vs. 3.6, P < 0.05) compared to non-frail individuals. Genetic correlation between frailty and OA was significant (rg = 0.532, P = 4.230E-88). Cross-trait analyses identified 42 genomic loci and 138 genes shared between the conditions. COLOC analysis revealed 2 pleiotropic loci, while TWAS identified 27 significant shared genetic expressions in whole blood and musculoskeletal tissue. Bidirectional MR indicated that OA increases the risk of frailty (IVW: beta: 0.13, P = 1.52E-08) and vice versa (IVW: beta: 0.73, P = 1.66E-04). Frail individuals exhibit more severe imaging features of OA. The shared genetic basis between OA and frailty suggests an intrinsic link, providing new insights into the relationship between these conditions.

Metabotropic glutamate receptor 7 (mGlu₇) is a G protein-coupled receptor that is preferentially found in the active zone of neurotransmitter release in the central nervous system (CNS). mGlu₇ plays a vital role in memory, learning, and neuronal development, rendering it a potential target for treating epilepsy, depression, and anxiety. The development of noninvasive imaging ligands targeting mGlu₇ could help elucidate the functional significance of mGlu₇ and accelerate drug discovery for neurological and psychiatric disorders. In this report, a novel carbon-11 labeled positron emission tomography (PET) tracer designated [¹¹C]18 (codenamed MG7-2109) was synthesized via ¹¹C-methylation in 23% decay-corrected radiochemical yield (RCY). In vitro serum stability, serum protein binding, in vitro autoradiography and ex vivo biodistribution studies of [¹¹C]18 were conducted. Preliminary PET imaging results revealed a homogeneous distribution of [¹¹C]18 and rapid clearance in rodent brains. This study provides valuable insights into the development of mGlu₇-targeted PET tracer based on an isoxazolo(5,4-c)pyridine scaffold.

Electrochemical separation technology has brought a renaissance in the field of nuclear medicine towards obtaining clinical-grade radiometals for preparation of a wide variety of radiopharmaceuticals. This article is a comprehensive summary of the electrochemical processes developed for the separation of radiometals that could be used for diagnostic or therapeutic applications in nuclear medicine. For using electrochemistry as a tool for the separation of radiometals, intricate knowledge is essential to understand the basic parameters of electrochemical separation processes which include applied potential, selection of electrolyte, choice of the electrode, the temperature of the electrolyte, pH of the electrolyte and time of electrolysis. The advantages of the electrochemical separation approach over the other conventional methodologies such as solvent extraction, column chromatography, sublimation, etc., have also been discussed. The latest research and development from our laboratory on electrochemical methodologies developed for separation of ⁹⁰Y from ⁹⁰Sr, ¹⁸⁸Re from ¹⁸⁸W, ^99mTc from ⁹⁹Mo, ⁴⁷Sc from ⁴⁶Ca, ⁴⁵Ca from ⁴⁶Sc,¹⁵³Sm from ¹⁵⁴Eu, ¹⁶⁹Er from ¹⁶⁹Yb, ¹⁷⁷Lu from Yb and ^132/135La from Ba have been described. In all the cases, the final product is obtained either in a 'no-carrier-added' (NCA) form or free from inextricable impurities and thus found suitable for formulation of radiopharmaceuticals.

Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory condition of the gastrointestinal (GI) tract that presents complex diagnostic and management challenges. Early detection and treatment of IBD is paramount, as IBD can present with serious complications, including bowel perforation, arthritis, and colorectal cancer. Most forms of diagnosis and therapeutic management, like ileocolonoscopy and upper endoscopy are highly invasive and require extensive preparation at great discomfort to patients. 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging can be a potential solution to the current limitations in imaging for IBD. This review explores the utility and limitations of various imaging modalities used to detect and manage IBD including ileocolonoscopy, magnetic resonance enterography (MRE), gastrointestinal ultrasound (IUS), and 18F-FDG-PET/computed tomography (18F-FDG-PET/CT) and magnetic resonance imaging (18F-FDG-PET/MR). This review has an emphasis on PET imaging and highlights its benefits in detection, management, and monitoring therapeutic response of UC and CD.

Microglia, a type of immune cells of the central nervous system, play a critical role in the pathophysiology of neurodegenerative disorders including Alzheimer's disease (AD). Recently, efforts for drug discovery have focused on modifying the function of microglia to halt AD progression. One such effort targets a multifaceted kinase called receptor-interacting protein kinase 1 (RIPK1) that controls inflammation and cell death. Pharmaceutical inhibition of RIPK1 in microglia prevents their homeostatic status from transforming to disease-associated status. Thus, RIPK1 inhibitors can be a therapeutic agent for halting AD progression. Therefore, in vivo imaging of RIPK1 may be a useful biomarker of AD. Recently, a novel PET ligand, [¹¹C]TZ7774, targeting RIPK1 was developed showing its ability to enter the brain and an increased uptake in the spleen of acute inflammation model mice. However, they have not yet shown direct evidence of specific binding of [¹¹C]TZ7774 to RIPK1 in the brain. In this study, we replicated the synthesis of [¹¹C]TZ7774 and examined its specific binding in the rat and human brain. Our studies with this ligand failed to detect sufficient specific binding of [¹¹C]TZ7774 to RIPK1 in the brain neither by PET imaging with healthy and acute inflammation model rats, nor by autoradiography with healthy rat and human brain slices. Our results suggest that the RIPK1 ligand, [¹¹C]TZ7774, is unlikely to be useful in humans. Future studies are warranted to develop more optimal radioligands for PET imaging of RIPK1.

Background: High-affinity radiohybrid PSMA-targeting radiopharmaceutical ¹⁸F-flotufolastat (¹⁸F-rhPSMA-7.3) is newly approved for diagnostic imaging of prostate cancer. Here, we conduct a post hoc analysis of two phase 3 studies to quantify ¹⁸F-flotufolastat uptake in a range of normal organs.

Methods: All 718 evaluable ¹⁸F-flotufolastat scans from LIGHTHOUSE and SPOTLIGHT were re-evaluated. Additionally, patients' medical records were reviewed and any patients with high tumor burden (PSA>20 ng/mL), altered biodistribution (e.g., chronic kidney disease), major anatomical changes to normal organs (e.g., nephrectomy), or any other history of cancer were excluded. A medical physicist defined volumes of interest over specific organs for evaluation of SUV_mean and SUV_peak per PERCIST 1.0 criteria. Normally distributed data are reported as mean (SD) and non-normally distributed data as median (IQR). The co-efficient of variation (CoV; calculated as SD/mean for normally distributed data and IQR/median for non-normally distributed data) was used to quantify variability of SUV metrics.

Results: In total, scans from 546 patients (244 primary, 302 recurrent) were eligible for this analysis. All organs were considered to be normally distributed except for the bladder and spleen. In the liver, the mean SUV_mean was 6.7 (SD 1.7), CoV 26%, while the bladder median SUV_mean was 10.6 (IQR 11.9), CoV 112%. The mean SUV_peak in the liver was 8.2 (SD 2.1), CoV 26% and median SUV_peak in the bladder was 16.0 (IQR 18.5), CoV 116%.

Conclusions: Physiological ¹⁸F-flotufolastat uptake in normal organs was broadly consistent with other renally-cleared radiopharmaceuticals, which may have clinically significant implications when considering patient selection for radioligand therapy. Additionally, the bladder median SUV_peak for ¹⁸F-flotufolastat was lower than that previously reported for ⁶⁸Ga-PSMA-11 and ¹⁸F-DCFPyL.

Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase family that regulates diverse biological processes including glucose metabolism, insulin activity and energy homeostasis. Dysregulation of GSK3 is implicated in the development of several diseases such as type 2 diabetes mellitus, Alzheimer's disease (AD), and various cancer types. In this study, we report the synthesis and evaluation of a novel positron emission tomography (PET) ligand compound 28 (codenamed [¹⁸F]GSK3-2209). The PET ligand [¹⁸F]28 was obtained via copper-mediated radiofluorination in more than 32% radiochemical yields, with high radiochemical purity and high molar activity. In vitro autoradiography studies in rodents demonstrated that this tracer exhibited a high specific binding to GSK3. Furthermore, PET imaging studies of [¹⁸F]28 revealed its ability to penetrate the blood-brain barrier (BBB).

Brain pharmacokinetic parametric imaging based on dynamic positron emission tomography (PET) scan is valuable in the diagnosis of brain tumor and neurodegenerative diseases. For short-axis PET system, standard blood input function (BIF) of the descending aorta is not acquirable during the dynamic brain scan. BIF extracted from the intracerebral vascular is inaccurate, making the brain parametric imaging task challenging. This study introduces a novel technique tailored for brain pharmacokinetic parameter imaging in short-axis PET in which the head BIF (hBIF) is acquired from the cavernous sinus. The proposed method optimizes the hBIF within the Patlak model via data fitting, curve correction and Patlak graphical model rewriting. The proposed method was built and evaluated using dynamic PET datasets of 67 patients acquired by uEXPLORER PET/CT, among which 64 datasets were used for data fitting and model construction, and 3 were used for method testing; using cross-validation, a total of 15 patient datasets were finally used to test the model. The performance of the new method was evaluated via visual inspection, root-mean-square error (RMSE) measurements and VOI-based accuracy analysis using linear regression and Person's correlation coefficients (PCC). Compared to directly using the cavernous sinus BIF directly for parameter imaging, the new method achieves higher accuracy in parametric analysis, including the generation of Patlak plots closer to the standard plots, better visual effects and lower RMSE values in the K_i (P = 0.0012) and V (P = 0.0042) images. VOI-based analysis shows regression lines with slopes closer to 1 (P = 0.0019 for K_i ) and smaller intercepts (P = 0.0085 for V). The proposed method is capable of achieving accurate brain pharmacokinetic parametric imaging using cavernous sinus BIF with short-axis PET scan. This may facilitate the application of this imaging technology in the clinical diagnosis of brain diseases.

Objective: To explore the connection between TGF-β1 expression and the survival of patients with head and neck squamous cell carcinoma (HNSCC), as well as whether non-invasive CT-based Radiomics can predict TGF-β1 expression in HNSCC patients.

Methods: Data on transcriptional profiling and clinical information were acquired from the TCGA database and subsequently categorized based on the TGF-β1 expression cutoff value. Based on the completeness of enhanced arterial phase CT scans, 139 HNSCC patients were selected. The PyRadiomics package was used to extract radiomic features, and the 3D Slicer software was used for image segmentation. Using the mRMR_RFE and Repeat LASSO algorithms, the optimal features for establishing the corresponding gradient enhancement prediction models were identified.

Results: A survival analysis was performed on 483 patients, who were divided into two groups based on the TGF-β1 expression cut-off. The Kaplan-Meier curve indicated that TGF-β1 was a significant independent risk factor that reduced patient survival. To construct gradient enhancement prediction models, we used the mRMR_RFE algorithm and the Repeat_LASSO algorithm to obtain two features (glrlm and ngtdm) and three radiation features (glrlm, first order_10percentile, and gldm). In both the training and validation cohorts, the two established models demonstrated strong predictive potential. Furthermore, there was no statistically significant difference in the calibration curve, DCA diagram, or AUC values between the mRMR_RFE_GBM model and the LASSO_GBM model, suggesting that both models fit well.

Conclusion: Based on these findings, TGF-β1 was shown to be significantly associated with a poor prognosis and to be a potential risk factor for HNSCC. Furthermore, by employing the mRMR_RFE_GBM and Repeat_LASSO_GBM models, we were able to effectively predict TGF-β1 expression levels in HNSCC through non-invasive CT-based Radiomics.

The purpose of this study is to investigate bone SPECT/CT and diffusion-weighted MR imaging (DWI) in medication-related osteonecrosis of the jaw (MRONJ), focusing on the correlation between standardized uptake values (SUVs) and apparent diffusion coefficient (ADC) values. Twenty-nine patients with MRONJ who underwent SPECT/CT and DWI were included in this study. SUVs (maximum and mean) with SPECT/CT, and ADC values (maximum, mean and minimum) with DWI were analyzed on characteristics in MRONJ, such as stage, location, medication and underlying disease, by Mann-Whitney U test. Furthermore, the correlation between SUVs and ADC values for characteristics in MRONJ were assessed by Spearman's rank correlation test for nonparametric data. A p-value lower than 0.05 was considered as statistically significant. SUVs and ADC values have no significant differences for all characteristics in MRONJ. Negative correlations were found in all cases and in stage 2 cases, and no correlations were found in stage 3 cases. In addition, negative correlations were found in maxillary cases, mandibular cases, non-bisphosphonate cases, osteoporosis cases, and malignant tumor cases. In conclusion, this study found multiple correlations between SUVs and ADC values in MRONJ, especially in stage 2. Suggesting that ADC values and SUVs may change with disease progression and the possibility of predicting MRONJ progression by SUVs and ADC values.