Positron Emission Tomography Research Articles

Fluorinated Coumarin Derivatives as Selective PET Tracer for MAO-B Imaging.

Monoamine oxidase-B (MAO-B), predominantly exists on the outer mitochondrial membrane of astrocytes, serves as a crucial biomarker for reactive astrocytes during neuroinflammatory responses and various neurodegenerative diseases. In this study, we synthesized a series of fluorinated coumarin derivatives and evaluated their structure-activity relationship and subtype selectivity for MAO-B. Following this, the preclinical bioevaluation containing in vivo positron emission tomography (PET) imaging and ex vivo autoradiography studies led to the identification of the novel PET tracer, [18F]8, which demonstrated high affinity for MAO-B (IC50 = 0.59 nM) and appreciable brain pharmacokinetics (SUVmax = 2.15 at 2 min, brain2min/60min = 7.67) in rats. Furthermore, the radioactivates from [18F]8 in regions of MAO-B expression could be effectively inhibited by Selegiline. All these positive findings supported that [18F]8 is a promising candidate for MAO-B PET imaging, which merits further evaluation.

Realization of high-end PET devices that assist conventional PET devices in improving image quality via diffusion modeling

PurposeThis study aimed to implement high-end positron emission tomography (PET) equipment to assist conventional PET equipment in improving image quality via a distribution learning-based diffusion model.MethodsA diffusion model was first trained on a dataset of high-quality (HQ) images acquired by a high-end PET device (uEXPLORER scanner), and the quality of the conventional PET images was later improved on the basis of this trained model built on null-space constraints. Data from 180 patients were used in this study. Among them, 137 patients who underwent total-body PET/computed tomography scans via a uEXPLORER scanner at the Sun Yat-sen University Cancer Center were retrospectively enrolled. The datasets of 50 of these patients were used to train the diffusion model. The remaining 87 cases and 43 PET images acquired from The Cancer Imaging Archive were used to quantitatively and qualitatively evaluate the proposed method. The nonlocal means (NLM) method, UNet and a generative adversarial network (GAN) were used as reference methods.ResultsThe incorporation of HQ imaging priors derived from high-end devices into the diffusion model through network training can enable the sharing of information between scanners, thereby pushing the limits of conventional scanners and improving their imaging quality. The quantitative results showed that the diffusion model based on null-space constraints produced better and more stable results than those of the methods based on NLM, UNet and the GAN and is well suited for cross-center and cross-device imaging.ConclusionA diffusion model based on null-space constraints is a flexible framework that can effectively utilize the prior information provided by high-end scanners to improve the image quality of conventional scanners in cross-center and cross-device scenarios.

Radical prostatectomy without prostate biopsy based on a noninvasive diagnostic strategy: a prospective single-center study.

Prostate biopsy is the most common approach for diagnosing prostate cancer (PCa); however, it has inherent limitations, such as the invasive procedure, postoperative complications, and false negative results. We aimed to provide a noninvasive diagnostic strategy for patients with highly suspected PCa and to evaluate the feasibility of performing biopsy-spared radical prostatectomy. This prospective study included a total of 57 patients between November 10, 2022, and December 1, 2023. All 57 patients underwent radical prostatectomy without prior prostate biopsy based on a noninvasive diagnostic strategy consisting of a diagnostic prediction model [comprised of the prostate imaging-reporting and data system (PI-RADS) score and prostate-specific antigen density (PSAD)] and the 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/computed tomography (CT) examination. The primary endpoint was the positive predictive value (PPV) of clinically significant PCa [the International Society of Urological Pathology (ISUP) grade ≥2, Gleason score ≥3 + 4]. The secondary endpoints were a PPV of any-grade PCa (ISUP grade ≥ 1, Gleason score ≥3 + 3) and high-grade PCa (ISUP grade ≥3, Gleason score ≥4 + 3), and the false positive rate of the diagnostic strategy. Of the 371 screened patients with clinically suspected PCa, 57 patients fulfilled the criteria and consented to participate in this study. The median PSAD level was 0.56 (0.42-0.82) ng/mL2; 13 (22.8%) patients were identified as having a PI-RADS score of 4, and 44 (77.2%) patients with a PI-RADS score of 5. The median SUVmax of 18F-PSMA-1007 PET/CT was 21.6 (15.8-33.0). For the 57 enrolled patients who received radical prostatectomy directly, the PPV of clinically significant PCa was 98.2% [56/57, 95% confidence interval (CI): 90.6-100%]. Only 1.8% (1/57, 95% CI: 0.0-9.4%) of patients were diagnosed with clinically insignificant PCa (ISUP grade = 1, Gleason score = 3 + 3). The PPV of any-grade PCa and high-grade PCa were 100% and 73.7% (42/57, 95% CI: 60.3-84.5%), respectively. No one had a false positive result. We proposed a noninvasive diagnostic strategy consisting sequentially of a diagnostic prediction model and the 18F-PSMA-1007 PET/CT examination for diagnosing PCa. Despite some limitations, our initial findings suggest the potential feasibility of radical prostatectomy without prior prostate biopsy.

Brain Imaging and Cognitive Deficits in Psychiatric Disorders

Over the last three decades, various neuroimaging techniques, such as magnetic resonance imaging (MRI), functional MRI, and positron emission tomography (PET), have played an essential role in improving our understanding of the pathogenesis of neuropsychiatric disorders [...]

[89Zr]Zr-DFO-TOC: a novel radiopharmaceutical for PET imaging of somatostatin receptor positive neuroendocrine tumors

BackgroundNeuroendocrine tumors (NETs) are clinically diverse types of tumors that can arise anywhere in the body. Previous studies have shown that somatostatin receptors (SSTRs) are overexpressed on NET cell membranes relative to healthy tissue, allowing for tumor targeting through radiolabeled somatostatin analogs (SSAs). This work aims to develop a novel 89Zr-labeled tracer incorporating the SSA, octreotide (TOC), for positron emission tomography (PET) imaging of SSTR + NETs and predictive dosimetry calculations, leveraging the excellent nuclear (t½ = 3.27 days, β+ = 22.3%, β+avg = 395.5 keV) and chemical characteristics (+ 4 oxidation state, preferential coordination number of 7/8, favorable aqueous chemistry) of 89Zr. In combination with 89Zr, the known radiochemistry with the chelator deferoxamine (DFO) gives reason to believe that this radiopharmaceutical incorporating an octreotide conjugate will be successful in studying the suitability of detecting SSTR + NETs.ResultsRadiochemical tracer assessment indicated that amounts as low as 0.1 nmol DFO-TOC can be effectively radiolabeled with 89Zr, while maintaining ≥ 95% radiochemical yield. The stability of the compound was found to maintain radiochemical yields of 89.6% and 88.7% on the benchtop and in mouse serum, respectively, after 9 days. Receptor binding and competitive receptor blocking assays compared AR42J (high SSTR expression), PC-3 (moderate SSTR expression), and PANC-1 (minimal SSTR expression) cell lines at time points up to 6 days. In vitro studies demonstrated highest uptake in AR42J cells, and statistically significant differences in tracer uptake were seen after 1 h. Internalization assays showed maximum internalization after 3 h for all cell lines.ConclusionsIn this work, [89Zr]Zr-DFO-TOC was synthesized with radiochemical yields ≥ 95% and was found to remain stable in vitro at extended time points. In vitro cell studies demonstrated a statistically significant difference between receptor binding and blocking experiments. The development of this work shows potential to positively impact patient care through the predictive dosimetry calculations for the FDA-approved therapeutic agent [177Lu]Lu-DOTA-TATE, while allowing for imaging at extended timepoints and should be studied further.

Prolonged fecal shedding of replication-competent virus, lasting immune activation, and intestinal inflammation in a rhesus macaque after experimental SARS-CoV-2 infection

Infection of an adult rhesus macaque with SARS-CoV-2 led to viral RNAemia in nose, throat, and lungs. The animal also presented extended fecal shedding of viral genomic and subgenomic messenger RNA and replication-competent virus for more than 3 weeks after infection. Positron emission tomography revealed increased intestinal glucose metabolism which was histologically related to inflammation of the ileum. These findings highlight the potential of the virus to cause gastrointestinal infections in macaques like this is also regularly observed in COVID-19 patients and substantiates the probability of virus transmission via the fecal-oral route. This study further adds the importance of nonhuman primates as a valuable animal model to study SARS-CoV-2 infection in humans.

Desmoplastic Small Round Cell Tumor: a study of CT, MRI, PET/CT multimodal imaging features and their correlations with pathology

PurposeExploring the computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET)/CT Multimodal Imaging Characteristics of Desmoplastic Small Round Cell Tumor (DSRCT) to enhance the diagnostic proficiency of this condition.MethodsA retrospective analysis was performed on clinical data and multimodal imaging manifestations (CT, MRI, FDG-PET/CT) of eight cases of DSRCT. These findings were systematically compared with pathological results to succinctly summarize imaging features and elucidate their associations with both clinical and pathological characteristics.ResultsAll eight cases within this cohort exhibited abdominal-pelvic masses, comprising six solitary masses and two instances of multiple nodules, except for one case located in the left kidney, the remaining cases lacked a clear organ source. On plain images, seven cases exhibited patchy areas of low density within the masses, four cases showed calcification within the masses. Post-contrast imaging displayed mild-to-moderate, uneven enhancement. Larger masses displayed patchy areas without significant enhancement at the center. In the four MRI examinations, T1-weighted images exhibited uneven, low signal intensity, while T2-weighted images demonstrated uneven high signal intensity. Imaging unveiled four cases of liver metastasis, four cases of ascites, seven cases of lymph node metastasis, three cases of diffuse peritoneal thickening, and one case involving left ureter invasion with obstruction. In the FDG-PET/CT examinations of seven cases, multiple abnormal FDG accumulations were observed in the abdominal cavity, retroperitoneum, pelvis, and liver. One postoperative case revealed a new metastatic focus near the colonic hepatic region. The range of maximum standardized uptake values (SUVmax) for all lesions are 6.62–11.15.ConclusionsDSRCT is commonly seen in young men, and the imaging results are mostly multiple lesions with no clear organ source. Other common findings include intratumoral calcification, liver metastasis, ascites, peritoneal metastasis, and retroperitoneal lymph node enlargement. The combined use of CT, MRI and FDG-PET/CT can improve the diagnostic accuracy and treatment evaluation of DSRCT. However, it is imperative to underscore that the definitive diagnosis remains contingent upon pathological examination.

High spatial resolution PET detectors based on 10 mm × 10 mm linearly-graded SiPMs and 0.5 mm pitch LYSO arrays.

Position-sensitive silicon photomultipliers (PS-SiPMs) are promising photodetectors for ultra-high spatial resolution small-animal positron emission tomography (PET) scanners. This paper evaluated the performance of the latest generation of linearly-graded SiPMs (LG-SiPMs), a type of PS-SiPM, for ultra-high spatial resolution PET applications using LYSO arrays from two vendors. 
Approach: Two dual-ended readout detectors were developed by coupling LG-SiPMs to both ends of the two LYSO arrays. Each LG-SiPM has an active area of 9.8 mm × 9.8 mm. Both LYSO arrays consist of 20 × 20 arrays of 0.44 mm × 0.44 mm × 20 mm polished LYSOs with a pitch of 0.5 mm. The performance of the two detectors was compared in terms of flood histogram, energy resolution, timing resolution, and depth-of-interaction (DOI) resolutions.
Main results: Flood histograms showed clear identification of all LYSO elements except for some edge crystals due to the larger size of the LYSO arrays compared to the active area of the LG-SiPMs and the misalignment between LG-SiPMs and LYSO arrays in the assembled detectors. At a bias voltage of 37.0 V, the detectors utilizing the Tianle LYSO array and EBO LYSO array provided energy resolutions of 17.5 ± 2.2 % and 18.6 ± 2.0 %, timing resolutions of 0.75 ± 0.03 ns and 0.78 ± 0.03 ns, and DOI resolutions of 2.16 ± 0.15 mm and 2.31 ± 0.12 mm, respectively. 
Significance: The results presented in this paper demonstrate that the new generation LG-SiPMs are promising photodetectors for ultra-high spatial resolution small-animal PET scanner applications.

Modern Thyroid Cancer Diagnosis: A Review of AI-Powered Algorithms for Detection and Classification

Thyroid nodules are one of the most common abnormalities in the thyroid gland, which are often harmless in nature (benign), but in a few unfortunate instances, they may be fatal (malignant). This review explores recent advancements in artificial intelligence (AI) applied to thyroid cancer detection and classification, with a focus on machine learning, deep learning, and image processing techniques. We provide a comprehensive evaluation of AI applications across key imaging modalities—Ultrasonography (USG), Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET/CT)—as well as cytopathological analysis using Fine Needle Aspiration Biopsy (FNAB). By critically examining studies on AI-driven preoperative assessments, we highlight improvements in diagnostic accuracy, sensitivity, specificity and efficiency. This review also identifies current limitations in AI applications, including technical challenges and unresolved issues that hinder widespread clinical adoption. Although significant progress has been achieved, the integration of AI in clinical settings remains limited, as AI-based outputs currently serve as supportive tools rather than definitive diagnostic evidence. We discuss the potential of AI to transform thyroid cancer diagnostics by enhancing reliability and accessibility, while addressing the need for further research to develop a unified, robust and clinically trustworthy AI framework for thyroid cancer diagnosis.

Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system xc− radiotracer, [18F]FSPG, provides a sensitive and specific marker of NRF2 activation in orthotopic, patient-derived, and genetically engineered mouse models of NSCLC. We found a NRF2-related gene expression signature in a large cohort of NSCLC patients, suggesting an opportunity to preselect patients prior to [18F]FSPG imaging. Furthermore, we reveal that system xc− is a metabolic vulnerability that can be therapeutically targeted with an antibody-drug conjugate for sustained tumour growth suppression. Overall, our results establish [18F]FSPG as a predictive marker of therapy resistance in NSCLC and provide the basis for the clinical evaluation of both imaging and therapeutic agents that target this important antioxidant pathway.

Artificial Intelligence-Based Methodologies for Early Diagnostic Precision and Personalized Therapeutic Strategies in Neuro-Ophthalmic and Neurodegenerative Pathologies

Advancements in neuroimaging, particularly diffusion magnetic resonance imaging (MRI) techniques and molecular imaging with positron emission tomography (PET), have significantly enhanced the early detection of biomarkers in neurodegenerative and neuro-ophthalmic disorders. These include Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. This review highlights the transformative role of advanced diffusion MRI techniques—Neurite Orientation Dispersion and Density Imaging and Diffusion Kurtosis Imaging—in identifying subtle microstructural changes in the brain and visual pathways that precede clinical symptoms. When integrated with artificial intelligence (AI) algorithms, these techniques achieve unprecedented diagnostic precision, facilitating early detection of neurodegeneration and inflammation. Additionally, next-generation PET tracers targeting misfolded proteins, such as tau and alpha-synuclein, along with inflammatory markers, enhance the visualization and quantification of pathological processes in vivo. Deep learning models, including convolutional neural networks and multimodal transformers, further improve diagnostic accuracy by integrating multimodal imaging data and predicting disease progression. Despite challenges such as technical variability, data privacy concerns, and regulatory barriers, the potential of AI-enhanced neuroimaging to revolutionize early diagnosis and personalized treatment in neurodegenerative and neuro-ophthalmic disorders is immense. This review underscores the importance of ongoing efforts to validate, standardize, and implement these technologies to maximize their clinical impact.

Primary perianal alveolar rhabdomyosarcoma with uncommon metastatic sites: a case report and follow-up using 18F-FDG PET/CT

BackgroundRhabdomyosarcoma (RMS), a rare pediatric soft tissue neoplasm, predominantly develops in late childhood and adolescence with no discernible gender bias. Alveolar rhabdomyosarcoma (ARMS) stems from mesenchymal cells and may develop most frequently in the trunk, extremities, and head/neck areas, while occurrences in the pelvic cavity are less frequent. The manifestation is typically characterized by a high rate of aggressive metastasis and a poor overall survival prognosis.Case reportWe present the case of an 11-year-old girl with ARMS initially presenting with a perianal mass. The diagnostic workup included MRI and PET/CT, which highlighted the tumor’s aggressive nature and metastatic potential. Subsequent metastases to the pleura, lymph nodes, and, less frequently, to the bone were detected using 2-deoxy-2-[fluorine-18]-fluoro-D-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) imaging. The patient underwent a multi-regimen chemotherapy protocol but showed an incomplete response, indicating a poor prognosis.ConclusionThis report presents a rare case of ARMS primarily located in the perianal region with multiple metastases, including the uncommon occurrence of bone metastasis, which illustrates the challenges in diagnosing and treating ARMS, emphasizing the need for accurate and early diagnosis, advanced imaging for disease assessment, and more effective treatment strategies. 18F-FDG PET/CT imaging highlights its preeminence in detecting multiple rare metastatic lesions. However, the persistent disease activity despite treatment highlights the need for further research into the biology of ARMS and the development of novel therapeutics to improve patient outcomes.

Post mortem validation and mechanistic study of UCB-J in progressive supranuclear palsy patients' brains.

Progressive supranuclear palsy (PSP) is a devastating 4R tauopathy affecting motor functions and is often misdiagnosed/underdiagnosed due to a lack of specific biomarkers. Synaptic loss is an eminent feature of tauopathies including PSP. Novel synaptic positron emission tomography tracer UCB-J holds great potential for early diagnosis; however, there is a substantial knowledge gap in terms of the mechanism and the extent and nature of synaptic loss in PSP. Here, we report an in-depth post mortem validation and mechanistic study of UCB-J in PSP and control brains using radioligand/autoradiography binding studies, alongside biochemical correlation analyses of synaptic markers. 3H-UCB-J targeted synaptic vesicle protein 2A protein with high specificity and demonstrated a distinct interrelation with synaptic markers in PSP patients' brain regions. The loss of UCB-J binding in the early and severely affected globus pallidus of PSP patients' brains revealed deficits of glutamate/GABAergic synaptic terminals. Cortical and subcortical 4R tau load differentially impacted synaptic marker profiles across PSP patients, warranting further investigation. UCB-J targeted synaptic vesicle protein 2A with high specificity in progressive supranuclear palsy (PSP) brains and demonstrated a conserved single nM binding site across different brain regions. UCB-J depicted prominent synaptic loss at the synaptosome levels and revealed deficits of glutamate/GABAergic synaptic terminals in the early affected globus pallidus of PSP brains as compared to the control. Cortical and subcortical 4R tau load distinctly influenced synaptic markers profile across PSP patients and highlighted that presynaptic "ubiquitous" markers individually might not be able to represent the complete state of synaptic deficits/loss in PSP brains.

Deciphering 18F-DOPA uptake in SDH-related head and neck paragangliomas: a radiomics approach.

To investigate the influence of germline succinate dehydrogenase (SDHx) pathogenic variants on 6-[18F]-fluoro-3,4-dihydroxyphenylalanine (18F-DOPA) Positron Emission Tomography (PET) radiomic signature of head and neck paragangliomas (HNPGLs). Forty-seven patients (20 SDH pathogenic variants carriers) harboring 55 HNPGLs were retrospectively included. HNPGLs were delineated using Nestle adaptive threshold. 128 radiomic features were extracted and harmonized to correct for batch effects. Principal Component Analysis (PCA) was performed to remove redundancy and avoid collinearity. The most representative feature of each component was tested with multivariate stepwise logistic binary regression analysis (LBRA) to identify variables predictive of genetic status. 18F-DOPA Positron Emission Tomography/Computed Tomography (PET/CT) detected 28/29 carotid body HNPGLs, 23/23 jugulotympanic HNPGLs, and 4/4 vagal HNPGLs. SUVmax was significantly higher in SDH-related HNPGLs (p = 0.003). PCA allowed identification of 4 Components. The most representative variables of Component 1 and 2 (including intensity and intensity-related textural features, and not intensity-related textural features, respectively) were Intensity-based (IB)-SUVmedian and Grey Level Run Length Matrix-Long Run Low Gray Level Emphasis (GLRLM-LRLGLE). SDHx HNPGLs exhibited higher activity scores and more homogeneous texture. At patient level, SDHx cases showed significantly higher IB-SUVmedian values (p < 0.001), and lower GLRLM-LRLGLE than sporadic patients (p = 0.005). IB-SUVmedian was found to be an independent predictor of genetic status at lesion (71.0%) and patient level (77.8%). The present study pioneers the application of 18F-DOPA PET radiomics for HNPGLs, suggesting the influence of germline SDH pathogenic variants on 18F-FDOPA uptake intensity and textural heterogeneity. Integrating radiomics with genetic data provides new insights into the correlation between PET features and underlying molecular dysregulation.

Identification of novel tau positron emission tomography tracers for chronic traumatic encephalopathy by comprehensive in silico screening and molecular dynamics simulation.

Chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive mild traumatic brain injury, is characterized neuropathologically by abnormal hyperphosphorylated tau accumulation. Early detection of tau deposition in the brain is crucial for the prevention and evaluation of CTE. Positron emission tomography (PET) tracers can image specific proteins, while the optimal PET tracer for CTE tau fibrils remains unidentified. In this study, structure-based virtual screening and CNS PET MPO algorithms were utilized to identify candidates for novel tau PET tracers from 23 000 compounds in the ChemDiv CNS BBB library. A total of 8 μs molecular dynamics simulations were then employed to evaluate their binding affinity and atomic-level interaction with CTE tau protofibrils. The results indicate that V017-7820 (CNS-4), S776-0061 (CNS-12), S567-0465 (CNS-18), and T828-0465 (CNS-25) exhibit higher docking scores and binding free energies with CTE tau protofibrils while also satisfying the fundamental physicochemical properties of PET tracers. Further simulation analyses reveal that CNS-4 has the strongest binding affinity to tau protofibrils among the four compounds. Hydrophobic, π-π stacking, and hydrogen bonding interactions are the primary driving forces for the binding of these compounds to CTE tau protofibrils. In particular, CNS-12 and CNS-25 exhibit more intense hydrophobic and π-π stacking interactions, whereas CNS-4 and CNS-25 exhibit stronger hydrogen bonding interactions. This study identifies promising lead compounds for tau PET tracers and highlights their mechanism of binding to CTE tau protofibrils, which provides new insights for further screening and development of novel PET tracers for CTE diagnosis.

Synthesis and Preclinical Evaluation of Dual-Specific Probe Targeting Glypican-3 and Prostate-Specific Membrane Antigen for Hepatocellular Carcinoma PET Imaging.

Positron emission tomography (PET) is a promising modality for early diagnosis, accurate detection, and staging of hepatocellular carcinoma (HCC). Hereby, a dual-specific probe targeting Glypican-3 (GPC3) and prostate-specific membrane antigen (PSMA) was evaluated for HCC PET imaging. The probe was prepared by conjugating TJ12P2, a GPC3-targeting peptide previously reported by our group, to a highly potent PSMA inhibitor via a polyethylene glycol linker and further tethered to the 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelator. The resultant probe, NOTA-TJ12P2-PSMA, abbreviated as T2P, was labeled with gallium-68 and fluorine-18, respectively, and evaluated in murine HCC models of various levels of GPC3 and PSMA expression. Targeting specificity was confirmed by blocking studies. The synthesized [68Ga]Ga-T2P and [18F]AlF-T2P were stable in saline and fetal bovine serum for over 2 h, and bound to their respective targets with high affinity and specificity in cell assays. PET imaging at 60 min postinjection (p.i.) showed that [68Ga]Ga-T2P exhibited higher uptake (1.75 ± 0.16%ID/g) in Huh7 models with high expression of GPC3 and PSMA than gallium-68 labeled TJ12P2 (1.25 ± 0.07%ID/g, p < 0.01) or gallium-68 labeled PSMA-617 (1.07 ± 0.06%ID/g, p < 0.001). The uptake of [68Ga]Ga-T2P in Huh7 tumors was higher than that in PC-3 tumors with low expression of GPC3 or PSMA (0.55 ± 0.24%ID/g, p < 0.01). The uptake of [18F]AlF-T2P or [68Ga]Ga-T2P in the Huh7 tumor was substantially blocked by TJ12P2, TJ12P2 + PSMA, or T2P, but only partially blocked by PSMA. And the PSMA and TJ12P2 monomer blocking effect was less than that of TJ12P2 + PSMA and T2P. [18F]AlF-T2P had higher tumor-to-muscle ratios than [68Ga]Ga-T2P at 90 min postinjection (4.31 ± 0.10 vs 3.80 ± 0.17, p < 0.05) in Huh7 tumor models. To conclude, radiolabeled T2P exhibited a higher uptake and longer retention in Huh7 tumors than its monomeric counterparts. PET imaging via gallium-68 and fluorine-18 labeled T2P showed a similar imaging quality with comparable signal-to-background ratios. Our results demonstrate that T2P is a promising tool for future clinical diagnosis of HCC.

Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.

Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA. A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%. Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; P=0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; P=0.94; median, 0.31% [IQR, 0.17%-0.71%]; P=0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; P<0.001; median, 0.25% [IQR, 0.15%-0.52%]; P<0.001). HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.

Python technology and its applications in radiomics

Python, developed by Guido van Rossum, is favored for its simplicity and extensive ecosystem of libraries, which facilitate efficient coding and integration with other programming languages. Here, we aim to explore and summarize the role of Python in radiomics, a field focused on extracting and analyzing quantitative features from medical imaging to improve disease characterization and treatment evaluation. Radiomics addresses the complexities of tumor heterogeneity by transforming imaging data from modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) into actionable insights, often using statistical methods and machine learning techniques. Its primary applications include differentiating between benign and malignant tumors and predicting treatment outcomes, etc. Python is integral to several stages of radiomics, including image acquisition, region of interest (ROI) segmentation, feature extraction, and statistical analysis. By utilizing libraries such as PyRadiomics and Scikit-learn, researchers can significantly enhance the accuracy and efficiency of their analyses. Looking forward, Python holds considerable promise in radiomics, especially with ongoing advancements in medical imaging and big data. However, challenges such as data standardization, model interpretability, and patient privacy protection must be addressed to fully unlock its potential for improving diagnostic precision and patient outcomes.

Isopeptidic Desferrioxamine Analogues: The Role of Hydroxamate Spacing for Chelation of Zr4.

[89Zr]Zr4+ is a radionuclide of increasing clinical relevance for PET (positron emission tomography). However, an ideal chelator for stable Zr-chelation remains to be discovered. This study describes the solid-phase synthesis of octadentate Zr-chelators based on an isopeptidic (ip) scaffold derived from the natural siderophore desferrioxamine (DFOB). Several analogues with different spacers separating the chelating hydroxamates have been prepared and converted to [89Zr]Zr-complexes. The stability of these complexes was evaluated in human serum and in competition to excess of competing chelators. The assays revealed a beneficial effect of long hydroxamate spacing (9 atoms). Shorter spacing led to a decrease in complex stability. The most stable [89Zr]Zr-ipDFO complex had a high stability in challenging competition experiments with a large excess of EDTA for 72 h as determined by radio TLC and LC/MS. The straightforward synthesis, high complex stability and a modular character make ipDFO derivatives promising chelators for applications in targeted PET.

Evaluation and clinical applicability of angiography-derived assessment of coronary microcirculatory resistance: a [15O]H2O PET study.

The introduction of wire-free microcirculatory resistance index from functional angiography (angio-IMR) promises swift detection of coronary microvascular dysfunction, however it has not been properly validated. We sought to validate angio-IMR against invasive IMR and PET derived microvascular resistance (MVR). Moreover, we studied if angio-IMR could aid in the detection of ischemia with non-obstructive coronary arteries (INOCA). In this investigator-initiated study symptomatic patients underwent [15O]H2O positron emission tomography (PET) and invasive angiography with 3-vessel fractional flow reserve (FFR). Invasive IMR was measured in 40 patients. Angio-IMR and QFR were computed retrospectively. MVR was defined as the ratio of mean distal coronary pressure to PET derived coronary flow. PET and QFR/angio-IMR analyses were performed by blinded core labs. The right coronary artery was excluded. A total of 211 patients (mean age 61 ± 9, 148 (70%) male) with 312 vessels with successful angio-IMR analyses were included. Angio-IMR correlated moderately with invasive IMR (r = 0.48, p < 0.01), whereas no correlation was found between angio-IMR and MVR (r=-0.07, p = 0.25). Angio-IMR did not differ for vessels without obstructive coronary artery disease (CAD) (FFR-) but with reduced stress perfusion (PET+) compared to vessels without obstructive CAD (FFR-) with normal stress perfusion (PET-) (median 28.19 IQR 20.42-38.99 vs. 31.67 IQR 23.47-40.63, p = 0.40). Angio-IMR correlated moderately with invasively measured IMR, whereas angio-IMR did not correlate with PET derived MVR. Moreover, angio-IMR did not reliably identify patients with INOCA.