Fluorodeoxyglucose Positron Emission Tomography Research Articles

195 Targeting Thalamocortical Circuits For Closed-Loop Stimulation in Lennox-Gastaut Syndrome

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy associated with frequent seizures, cognitive impairment, and high burden of care. Electrical stimulation of the thalamus can be an effective treatment for LGS, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. METHODS: Brain network maps from 3 group-level studies of LGS were averaged to define the area of peak overlap: combined electroencephalography-functional MRI (EEG-fMRI) of paroxysmal fast activity, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) of hypometabolism, and structural connectivity associated with efficacy in a previous trial of deep brain stimulation. The resulting “hotspot” was used as a seed in a normative fMRI connectivity analysis to identify connected networks. Two patients underwent bilateral thalamocortical implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analyzed for presence and synchrony of epileptiform activity. RESULTS: Peak overlap was in bilateral premotor cortex. Functional connectivity of this hotspot revealed a network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-fMRI and FDG-PET. Intracranial electrophysiology showed characteristic epileptiform activity of LGS in the cortical hotspot that preceded or co-occurred with similar thalamic activity. CONCLUSIONS: Premotor cortex shows peak involvement in LGS, and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for neuromodulation therapies, including thalamocortical stimulation. Compared to thalamus-only stimulation, addition of this cortical target may allow more rapid detections and responsive stimulations of seizures, and broader modulation of the brain network underlying LGS to achieve greater seizure control.

(18)F-fluorodeoxyglucose uptake by positron emission tomography in patients with IPAH and CTEPH.

Pulmonary arterial hypertension (PAH) is driven by pathologies associated with increased metabolism such as pulmonary revascularization, vasoconstriction and smooth muscle cell proliferation in pulmonary artery wall. 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) is an imaging technique sensitive to glucose metabolism and might be considered as a non-invasive method for diagnosis due to significant role of inflammation in idiopathic pulmonary artery hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study aimed to investigate the role of PET/CT imaging of patients with IPAH and CTEPH as an alternative diagnosis method. Demographic characteristics, FDG uptake in lungs, pulmonary artery and right ventricle (RV) of 17 patients (10 IPAH, 7 CTEPH), and 30 controls were evaluated. PET scanning, 6-min walk test, pro-BNP level, right heart catheterization of patients were performed both at the onsert and after 6-month PAH specific treatment. IPAH and CTEPH patients had significantly higher left lung FDG (p = 0.006), right lung FDG (p = 0.004), right atrial (RA) FDG (p < 0.001) and RV FDG (p < 0.001) uptakes than controls. Positive correlation was detected between the RV FDG uptake and the mean pulmonary artery pressure (mPAP) (r = 0.7, p = 0.012) and between the RA FDG uptake and the right atrial pressure (RAP) (r = 0.5, p = 0.02). Increased RV FDG and RA FDG uptakes predicts the presence of pulmonary hypertension and correlates with mPAP and RAP, respectively, which are important indicators in the prognosis of PAH. Further studies are required whether FDG PET imaging can be used to diagnose or predict the prognosis of pulmonary hypertension.

Defecation after magnesium supplementation enhances cognitive performance in triathletes

Constipation is correlated with diminished cognitive function, revealing a possible rectum-brain connection. In this counter-balanced crossover trial, 13 elite triathletes underwent a Stroop test to assess cognitive function and executive control. The Stroop test was conducted both with and without magnesium oxide intake, with a 1-week washout period between sessions. Oxygenation and blood distribution during the cognitive challenge were measured using Near-Infrared Spectroscopy (NIRS). Measurements were taken in both the prefrontal brain and the sub-navel region, where the highest glucose uptake was detected under the 18F-fluorodeoxyglucose Positron Emission Tomography (PET) scan. A significant reduction in completion time for the Stroop test was observed after defecation compared to the non-defecated condition (non-defecation: [27.1 ​± ​1.1] s; non-magnesium defecation: [24.4 ​± ​0.9] s; magnesium defecation: [23.4 ​± ​0.8] s, p ​< ​0.05). Stroop test performance was improved in all (100%, 13/13) of the participants after magnesium-induced defecation and most (69%, 9/13) of the participants after non-magnesium-induced defecation. While no alterations in oxygenation and blood distribution were observed in the prefrontal brain during the Stroop test, decreased oxygenation levels were observed in the sub-navel region under both defecated conditions, without significant changes in blood distribution (p ​< ​0.05). This data suggests an acute increase in oxygen consumption at this specific region. The result of this study suggests an unexplored causal link between the state of the rectum and cognitive performance. Magnesium supplementation to improved rectal emptying presents a novel application for optimizing cognitive function in athletes navigating intricate racing conditions.

Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine.

Despite evidence of the beneficial effects of cannabidiol (CBD) in animal models of cocaine use disorder (CUD), CBD neuronal mechanisms remain poorly understood. This study investigated the effects of CBD treatment on brain glucose metabolism, in a CUD animal model, using [18F]FDG positron emission tomography (PET). Male C57Bl/6 mice were injected with cocaine (20 mg/kg, i.p.) every other day for 9 days, followed by 8 days of CBD administration (30 mg/kg, i.p.). After 48 h, animals were challenged with cocaine. Control animals received saline/vehicle. [18F]FDG PET was performed at four time points: baseline, last day of sensitization, last day of withdrawal/CBD treatment, and challenge. Subsequently, the animals were euthanized and immunohistochemistry was performed on the hippocampus and amygdala to assess the CB1 receptors, neuronal nuclear protein, microglia (Iba1), and astrocytes (GFAP). Results showed that cocaine administration increased [18F]FDG uptake following sensitization. CBD treatment also increased [18F]FDG uptake in both saline and cocaine groups. However, animals that were sensitized and challenged with cocaine, and those receiving only an acute cocaine injection during the challenge phase, did not exhibit increased [18F]FDG uptake when treated with CBD. Furthermore, CBD induced modifications in the integrated density of NeuN, Iba, GFAP, and CB1R in the hippocampus and amygdala. This is the first study addressing the impact of CBD on brain glucose metabolism in a preclinical model of CUD using PET. Our findings suggest that CBD disrupts cocaine-induced changes in brain energy consumption and activity, which might be correlated with alterations in neuronal and glial function.

Application of 18F-FDG PET/CT imaging radiomics in the differential diagnosis of single-nodule pulmonary metastases and second primary lung cancer in patients with colorectal cancer.

It is crucially essential to differentially diagnose single-nodule pulmonary metastases (SNPMs) and second primary lung cancer (SPLC) in patients with colorectal cancer (CRC), which has important clinical implications for treatment strategies. In this study, we aimed to establish a feasible differential diagnosis model by combining 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) radiomics, computed tomography (CT) radiomics, and clinical features. CRC patients with SNPM or SPLC who underwent 18F-FDG PET/CT from January 2013 to July 2022 were enrolled in this retrospective study. The radiomic features were extracted by manually outlining the lesions on PET/CT images, and the radiomic modeling was realized by various screening methods and classifiers. In addition, clinical features were analyzed by univariate analysis and logistic regression (LR) analysis to be included in the combined model. Finally, the diagnostic performances of these models were illustrated by the receiver operating characteristic (ROC) curves and the area under the curve (AUC). We studied data from 61 patients, including 36 SNPMs and 25 SPLCs, with an average age of 65.56 ± 10.355 years. Spicule sign and ground-glass opacity (GGO) were significant independent predictors of clinical features (P = 0.012 and P < 0.001, respectively) to build the clinical model. We achieved a PET radiomic model (AUC = 0.789), a CT radiomic model (AUC = 0.818), and a PET/CT radiomic model (AUC = 0.900). The PET/CT radiomic models were combined with the clinical model, and a well-performing model was established by LR analysis (AUC = 0.940). For CRC patients, the radiomic models we developed had good performance for the differential diagnosis of SNPM and SPLC. The combination of radiomic and clinical features had better diagnostic value than a single model.

3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18F-FDG PET/CT Case Report.

New Psychoactive Substances (NPS) are modifying the drug scenario worldwide and have become a public health concern because of their toxicological profiles and their harmful physical/psychological effects. 3-Methoxy-Phencyclidine (3-MeO-PCP), a non-competitive antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors, belongs to the phencyclidine-like subfamily of arylcyclohexylamines and has gained attention for its toxic, sometimes fatal, effects. Despite several cases of intoxication and death reported in the literature, little is known about substance-induced psychotic disorders (SIP) and potential cognitive impairment following 3-MeO-PCP intake. This literature review aimed to summarize available evidence about 3-MeO-PCP mechanisms of action and physical and psychotropic effects and to spread preliminary findings about persistent psychotic symptoms and impaired cognitive functioning. Additionally, the case of an SIP is reported in a 29-year-old man with small oral intakes of 3-MeO-PCP over two weeks until a high dose ingestion. Psychometric and neuropsychological assessment and brain [18F]-fluorodeoxyglucose positron emission tomography integrated with computed tomography were used to support clinical description. Identifying and addressing the characteristic clinical features and neural substrates of NPS-induced psychoses might help clinicians with a more precise differentiation from other psychotic disorders. Although further studies are required, phenotyping the cognitive profile of NPS users might provide targets for tailored therapeutic approaches.

The Role of Magnetic Resonance Spectroscopy, Magnetic Resonance Perfusion and Positron Emission Tomography-Computed Tomography in Post-Radiotherapy Evaluation of Gliomas to Detect Recurrence

Abstract Background and Aim: In this article, the findings of magnetic resonance spectroscopy (MRS), magnetic resonance (MR) perfusion, and positron emission tomography (PET) will be compared and finally correlated with the histopathological examination in all patients having positive imaging findings. The sensitivity and specificity of MRS, MR perfusion, and PET in diagnosing residual/recurrent glioma would be estimated using the histopathological diagnosis as a gold standard. Materials and Methods: Twenty-nine cases of intracranial glioma that had undergone surgery, followed by adjuvant radiotherapy were enrolled in the study. All 29 patients underwent MRS, MR perfusion, and fluorodeoxyglucose (FDG) PET. Results: The sensitivity of MRS to detect recurrence was found to be 83.3% and specificity was 100%. The positive predictive value (PPV) and negative predictive value (NPV) were 100% and 33.3%, respectively. The diagnostic accuracy of MRS was found to be 84.6%. The sensitivity and specificity of MR perfusion to detect recurrence were 91.7% and 100%, respectively. The diagnostic accuracy of MR perfusion is 92.3%. The NPV of MR perfusion was found to be 50%. The sensitivity of PET scans to detect recurrence was 83.3% and specificity was 100%. The PPV of PET was 100% and the NPV was 33.3%. The diagnostic accuracy of the PET scan was found to be 84.6%. Conclusions: Our study shows that all three modalities are useful, however, MR perfusion study is better than MRS and FDG PET in detecting recurrence. MR contrast with perfusion and spectroscopy and FDG PET scan should be included in the protocol for radiotherapy-treated gliomas to differentiate between radiation necrosis, postradiotherapy gliosis, and recurrent/residual tumor.

The use of individual-based FDG-PET volume of interest in predicting conversion from mild cognitive impairment to dementia

BackgroundBased on a longitudinal cohort design, the aim of this study was to investigate whether individual-based 18F fluorodeoxyglucose positron emission tomography (18F-FDG-PET) regional signals can predict dementia conversion in patients with mild cognitive impairment (MCI).MethodsWe included 44 MCI converters (MCI-C), 38 non-converters (MCI-NC), 42 patients with Alzheimer’s disease with dementia, and 40 cognitively normal controls. Data from annual cognitive measurements, 3D T1 magnetic resonance imaging (MRI) scans, and 18F-FDG-PET scans were used for outcome analysis. An individual-based FDG-PET approach was applied using seven volumes of interest (VOIs), Z transformed using a normal FDG-PET template. Hypometabolism was defined as a Z score < -2 of regional standard uptake value ratio. For the longitudinal cognitive test scores, generalized estimating equations were used. A linear mixed-effects model was used to compare the temporal impact of cortical hypometabolism and cortical thickness degeneration.ResultsThe clinical follow-up period was 6.6 ± 3.8 years (range 3.1 to 16.0 years). The trend of cognitive decline could differentiate MCI-C from MCI-NC after 3 years of follow-up. In the baseline 18F-FDG-PET scan of the patients with MCI, medial temporal lobe (MTL; 94.7% sensitivity, 80.5% specificity) and posterior cingulate cortex (PCC; 89.5% sensitivity, 73.1% specificity) hypometabolism predicted conversion with high accuracy. 18F-FDG-PET hypometabolism preceded dementia conversion at an interval of 3.70 ± 1.68 years and was earlier than volumetric changes, with the exception of the MTL.ConclusionsOur finding supports the use of individual-based 18F-FDG-PET analysis to predict MCI conversion to dementia. Reduced FDG-PET metabolism in the MTL and PCC were strongly associated with future cognitive decline in the MCI-C group. Changes in 18F-FDG-PET occurred 1 to 8 years prior to conversion to dementia. Progressive hypometabolism in the PCC, precuneus and lateral temporal lobe, but not MTL, preceded MRI findings at the MCI stage.

Prognostic value of different discretization parameters in 18fluorodeoxyglucose positron emission tomography radiomics of oropharyngeal squamous cell carcinoma.

We aim to interrogate the role of positron emission tomography (PET) image discretization parameters on the prognostic value of radiomic features in patients with oropharyngeal cancer. A prospective clinical trial (NCT01908504) enrolled patients with oropharyngeal squamous cell carcinoma (; mixed HPV status) undergoing definitive radiotherapy and evaluated intra-treatment 18fluorodeoxyglucose PET as a potential imaging biomarker of early metabolic response. The primary tumor volume was manually segmented by a radiation oncologist on PET/CT images acquired two weeks into treatment (20Gy). From this, 54 radiomic texture features were extracted. Two image discretization techniques-fixed bin number (FBN) and fixed bin size (FBS)-were considered to evaluate systematic changes in the bin number ({32, 64, 128, 256} gray levels) and bin size ({0.10, 0.15, 0.22, 0.25} bin-widths). For each discretization-specific radiomic feature space, an LASSO-regularized logistic regression model was independently trained to predict residual and/or recurrent disease. The model training was based on Monte Carlo cross-validation with a 20% testing hold-out, 50 permutations, and minor-class up-sampling to account for imbalanced outcomes data. Performance differences among the discretization-specific models were quantified via receiver operating characteristic curve analysis. A final parameter-optimized logistic regression model was developed by incorporating different settings parameterizations into the same model. FBN outperformed FBS in predicting residual and/or recurrent disease. The four FBN models achieved AUC values of 0.63, 0.61, 0.65, and 0.62 for 32, 64, 128, and 256 gray levels, respectively. By contrast, the average AUC of the four FBS models was 0.53. The parameter-optimized model, comprising features joint entropy (FBN = 64) and information measure correlation 1 (FBN = 128), achieved an AUC of 0.70. Kaplan-Meier analyses identified these features to be associated with disease-free survival ( and , respectively; log-rank test). Our findings suggest that the prognostic value of individual radiomic features may depend on feature-specific discretization parameter settings.

Miliary tuberculosis diagnosed by diffuse hepatic uptake on PET/CT and transjugular liver biopsy.

The patient was an 81-year-old man. In his 20s, he had been treated with pharmacotherapy for pulmonary tuberculosis for 1 year. He presented to the Department of Respiratory Medicine with a chief complaint of dyspnea. The possibility of respiratory disease appeared to be low, but hepatic impairment was detected. The patient was thus referred to our department. Though the cause of hepatic impairment was unknown, the soluble interleukin-2 receptor level was elevated, suggesting malignant lymphoma. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) revealed diffuse, homogenous, intense FDG uptake in the entire liver, and transjugular liver biopsy confirmed the diagnosis. Histopathological examination revealed an epithelioid granuloma, and auramine staining was positive for bacilli suggestive of tuberculosis. CT revealed diffuse micronodular shadows in the lung, yielding a diagnosis of miliary tuberculosis. Therefore, the patient was prescribed antituberculosis medication by the Department of Respiratory Medicine. His subsequent clinical course was good. The miliary (hepatic) tuberculosis was typical based on the diffuse, homogenous, intense FDG uptake throughout the liver observed on PET-CT.

Abstract 4151: Development of a cancer-activated biologic imaging platform for early lung cancer diagnosis

Abstract Current modalities, such as LDCT and fluorodeoxyglucose positron emission tomography (FDG PET), for early lung cancer imaging, rely upon proxies resulting in poor specificity and/or sensitivity. They are also unreliable for discriminating benign versus malignant lesions resulting in the requirement of longitudinal analyses euphemistically called “watchful waiting”. Lung biopsies are marred by significant false negative rates and pose complications of collapsed lungs or bleeding in up to 22% of procedures and death rates up to 1%. To overcome these obstacles, Earli is developing a non-invasive, highly specific cancer-activated imaging platform that usurps dysregulated gene expression within malignancies to force only cancer cells to produce a synthetic biomarker that can be localized using PET imaging. EARLI-204 is a lipid nanoparticle that contains a DNA nanoplasmid comprised of a cancer-activated promoter driving selective expression of a functionally inactivated somatostatin receptor 2 (SSTR2fi) gene. Abrogation of internalization and signal transduction allows the safe use of SSTR2fi as an ectopically expressed PET reporter gene (PRG). Following administration, EARLI-204 transfects tumor and normal cells but transcriptional activation only within cancer cells results in selective cell-surface expression of SSTR2fi that can be imaged with FDA-approved SSTR2 PET tracers. H1299 human lung cancer cells engineered to express SSTR2 (H1299-SSTR2) revealed a discernable PET signal with as little as 31,000 engineered cells. Mixed cell titration studies using subcutaneous (SQ) tumors with H1299-SSTR2 and non-expressing H1299-wt cells suggest tumors with between 0.1% and 1% H1299-SSTR2 cells had a significant PET signal, compared to tumors with 100% H1299-wt. This result sets a benchmark transfection of ~1% to achieve a PET signal. Intratumoral (IT) dose titration of EARLI-204 revealed that 5 ug of EARLI-204 generates a significant PET signal. Consistent with the H1299-SSTR2 studies, IHC shows ~1% of tumor cells express the PRG at a 5 ug IT dose level. Furthermore, we measured 70 copies of EARLI-204 DNA per cell resulting in 22,629 SSTR2 mRNA copies/25 ng at a 5 ug IT dose level. IV dosing of EARLI-204 in SQ and intralung tumor models results in cancer-activated expression of SSTR2fi in both SQ and small (&amp;lt;4 mm) lung tumors with significantly increased (p &amp;lt; 0.05) PET signal. For lung tumors, analyses showed 1 copy of EARLI-204 DNA/cell resulting in 780 SSTR2 mRNA copies/25 ng. The results demonstrate an effective molecular imaging platform for drug discovery ranging from in vivo screening to building PK-PD-efficacy relationships and enabling human dose projection for the Earli PET localization drug. The benchmarks and findings established with this preclinical imaging pipeline are currently being evaluated in large animals such as dogs and pigs, and will be translated to humans in planned clinical trials. Citation Format: Mohammed Goryawala, Hung-Yu Henry Lee, Ling Tong, Trupti Patil, Alex Harwig, Chloe Xia, Suthara Ramachandran, Dariusz Wodziak, Dean Felsher, Tim Sproul, David Suhy. Development of a cancer-activated biologic imaging platform for early lung cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4151.

Abstract 4157: Combining hyperpolarized magnetic resonance and positron emission tomography to interrogate prostate cancer metabolism

Abstract Background: There is an unmet clinical need for imaging biomarkers to distinguish indolent from aggressive prostate cancer (PCa). Many advanced and aggressive PCa patients receiving anti-androgens (enzalutamide) develop resistance. It is hypothesized that dysregulated cell metabolism is a key driver for PCa progression and therapy resistance. Two pathways commonly involved in PCa are glycolysis and fatty acid metabolism. Therefore, metabolic imaging and metabolomics were performed on enzalutamide sensitive/resistant, Androgen Receptor dependent (AR+) and AR independent (AR-) patient derived xenograft (PDX) tumors. To interrogate both pathways, [1-13C]-pyruvate hyperpolarized magnetic resonance spectroscopy (HP-MRS) and [18F]-fluorodeoxyglucose positron emission tomography (18F-FDG) for glycolysis, and [18F]-fluoro-pivalic acid positron emission tomography (18F-FPIA) for fatty acid metabolism were employed. 1H Nuclear Magnetic Resonance (NMR) spectroscopy and liquid chromatography with tandem mass spectrometry (LC-MS-MS) were employed for validation purposes. Methods: [1-13C]-labeled pyruvic acid was hyperpolarized using a DNP HyperSense polarizer following standard protocol. Anatomical MRI and 13C-MRS were obtained on different PCa PDX mouse models at two different time points using a Bruker 7T scanner. The PDX models included AR+ enzalutamide sensitive (183-A, 180-30), AR+ enzalutamide resistant (274-4), and AR- (144-4, 114-B). The time points imaged were before and after 7 days of treatment with enzalutamide. 1H-NMR spectroscopy was performed on extracted tissue. Simultaneously, 18F-FPIA-PET imaging were acquired on the same models on an Albira trimodal PET station. Results: The dynamic metabolic flux ratio, lactate-to-pyruvate (Lac/Pyr) was determined in vivo and used as a treatment response marker. The Lac/Pyr ratios were significantly higher in resistant tumors compared to sensitive tumors (p&amp;lt;0.01). The enzalutamide sensitive group had a lower Lac/Pyr ratio after treatment, while the enzalutamide resistant group had a higher Lac/Pyr ratio. After treatment, there was also a decrease in [18F]-FDG uptake, corresponding to the HP-MRS data. This was expected as both Pyruvate and [18F]-FDG interrogate the glycolytic pathway. As for the fatty acid metabolic imaging, PET imaging also revealed that [18F]-FPIA is transported into the tumors, and we are currently exploring how its uptake varies between AR (+/-) PCa-PDX tumors and enzalutamide resistant/sensitive models. Ex vivo NMR and mass spectrometry-based metabolomics validated the in vivo HP-MRS data with higher lactate levels in drug resistant tumors. Conclusion: Combining HP-MRS and PET presents an exciting opportunity to realize imaging-based personalized medicine in different AR (+/-) PCa-PDX preclinical models by interrogating glycolysis and fatty acid oxidation pathways. Citation Format: Muxin Wang, José S. Enriquez, Prasanta Dutta, Jenny Han, Peter Shepherd, Daniel Frigo, Federica Pisaneschi, Pratip K. Bhattacharya. Combining hyperpolarized magnetic resonance and positron emission tomography to interrogate prostate cancer metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4157.

Abstract 2585: First in human study with a novel peptide binder to glypican-3, demonstrates high specificity as a PET imaging agent in patients with hepatocellular carcinoma

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The American Association for the Study of Liver Disease recommends surveillance for high-risk individuals with abdominal ultrasound, triple phase contrast CT or MRI. However, these imaging techniques have limited sensitivity in classifying lesions smaller than 2 centimeters. The use of [18F]FDG Positron Emission Tomography (PET) is constrained due to insufficient uptake by HCC lesions over background liver uptake. Hence, there is an urgent need for more precise radiotracers for HCC. This study introduces the development of a novel radiotracer that binds to glypican-3 (GPC3), a cell membrane-anchored oncofetal protein overexpressed in HCC with minimal normal tissue expression. Methods: [68Ga]Ga-RYZ-GPC3 is composed of a small macrocyclic peptide binder with high affinity to GPC3 linked with a tetraxetan moiety capable of chelating a variety of radioisotopes including positron-emitting 68Ga and other radiometals. The unlabeled binder to GPC3 was synthesized by the sponsor and provided to three imaging centers in India as part of investigator-initiated trials reviewed and approved by each site’s institutional review board and ethics committee. Labeling with 68Ga and quality checks of the product was performed locally at each center. Patients with high clinical suspicion or with confirmed HCC who gave informed consent received injections of 1.5-5.5 mCi of [68Ga]Ga-RYZ-GPC3 and underwent PET-CT scanning at predetermined intervals. Some patients underwent companion [18F]FDG PET-CT scans in accordance with local guidelines. Results: A total of 64 patients underwent [68Ga]Ga-RYZ-GPC3 PET-CT scans. The median age within the cohort was 61 (41-83), 22% were female. Liver cirrhosis was present in 72% of patients, attributed to hepatitis B, hepatitis C or NASH in 17%, 13% and 20% of cases. Notably, 92% of patients exhibited at least one positive lesion on [68Ga]Ga-RYZ-GPC3 scans. The median SUVmax of GPC3-avid liver lesions was 15.5 (range 1.1 to 137.0) while the median liver SUVmean was 1.6 (0.3-7.9). Physiologic uptake was predominantly observed in the kidneys, the primary route of clearance, with a median SUVmean of 10.9 (2.2-20.7). Additionally, 20 patients underwent [18F]FDG PET-CT scan for comparison. The median SUVmax of lesions on 68Ga-RYZ-GPC3 vs [18F]FDG PET was 11.0 (1.1-137.0) vs 3.8 (1.2-12.2). Conclusion: Early human imaging results in patients with HCC indicate that [68Ga]Ga-RYZ-GPC3 has high tumor lesion specificity compared to normal liverand demonstrates the potential of [68Ga]Ga-RYZ-GPC3 to improve detection of HCC over conventional [18F]FDG PET-CT. In addition, the binder could be complexed with a therapeutic radioisotope as a novel targeted therapeutic option for HCC. Further investigation of this first-in-class binder to HCC is warranted. Citation Format: Chandresakhar Bal, Sanjana Ballal, Kumar Kallur, Anna Karmann, Ye Yuan, Jessica Rearden, Kathryn Shah, Charlotte Lorenz, Susan Moran, Ken Song, Ishita Sen. First in human study with a novel peptide binder to glypican-3, demonstrates high specificity as a PET imaging agent in patients with hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2585.

End-of-treatment 18[F]-FDG PET can predict early progression in patients receiving bendamustine-rituximab for follicular lymphoma in first relapse: a prospective West Japan hematology Study Group (W-JHS) NHL01 trial.

Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.

Radiologic Parameters Predicting the Histologic Invasiveness of Pure Ground-Glass Nodules

BackgroundThis study aimed to investigate the diagnostic performance of combined computed tomography (CT) and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for predicting histologic invasiveness of pure ground-glass nodules (pGGNs). MethodsThe study analyzed 91 patients who underwent resection of pGGNs and examined the correlation of pathologic invasiveness with preoperative CT and FDG PET findings. ResultsOverall, 24, 36, and 31 patients had adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAD), respectively. Compared with AIS and MIA, IAD was significantly correlated with larger CT size (P = .001), maximum CT value (P = .026), and high maximum standardized uptake value (SUVmax; P < .001). Multivariable logistic analyses revealed that CT size (odds ratio [OR], 3.848; P = .019) and SUVmax (OR, 4.968; P = .009) were independent predictors of histologic invasiveness. Receiver operating characteristic curve analysis revealed that a cutoff CT size value of 18 mm predicted histologic invasiveness with a sensitivity and specificity of 65% and 80%, respectively; similarly, a cutoff SUVmax value of 1.5 predicted histologic invasiveness with a sensitivity and specificity of 61% and 90%, respectively. Of 20 lesions with CT size ≥18 mm and SUVmax ≥1.5, 16 (80%) were IAD. Of 54 lesions with CT size <18 mm and SUVmax <1.5, 46 (85%) were non-IAD lesions. Furthermore, all pGGNs with SUVmax ≥2.5 were IAD. ConclusionsCT size and SUVmax were significantly correlated with the histologic invasiveness of pGGNs. These factors may aid in determining optimal surgical procedures.

Texture Features of 18F-Fluorodeoxyglucose Positron Emission Tomography for Predicting Programmed Death-Ligand-1 Levels in Non-Small Cell Lung Cancer.

Background: Identifying programmed death-ligand-1 (PD-L1) expression is crucial for optimizing treatment strategies involving immune checkpoint inhibitors. However, the role of intratumoral metabolic heterogeneity specifically derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images in predicting PD-L1 expression in patients with newly diagnosed non-small cell lung cancer (NSCLC) remains unexplored. Here, we investigated the association between FDG PET texture features and PD-L1 expression by retrospectively analyzing the data of patients newly diagnosed with NSCLC who underwent FDG PET/CT scans and PD-L1 immunohistochemical staining before treatment. Methods: Patients were categorized based on their tumor proportion scores (TPSs) into negative-, low-, and high-PD-L1 expression groups. We computed the maximum standardized uptake value and 31 texture features for the primary tumor from PET images and compared differences in parameters among the groups. Results: Of the 83 patients, 12, 45, and 26 were assigned to the negative-, low-, and high-PD-L1 expression groups, respectively. Six specific texture features (low gray-level run emphasis, short-run low gray-level emphasis, long-run high gray-level emphasis, low gray-level zone emphasis, high gray-level zone emphasis, and short-zone low gray-level emphasis) helped distinguish among all possible combinations. Conclusions: Our findings revealed that FDG PET texture features are potential imaging biomarkers for predicting PD-L1 expression in patients newly diagnosed with NSCLC.

Total lesion glycolysis by 18F-fluorodeoxyglucose positron emission tomography predicts tumor aggressiveness in patients with extrahepatic bile duct carcinoma.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) parameters are prognostic factors in multiple malignancies. However, the prognostic value in bile duct carcinoma is unclear. We evaluated the impact of metabolic parameters of 18F-FDG-PET/CT in resectable extrahepatic bile duct carcinoma. We retrospectively reviewed the records of 100 patients with extrahepatic bile duct carcinoma who had undergone 18F-FDG-PET/CT and subsequent surgical resection between January 2017 and January 2023. We calculated maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and investigated their prognostic significance. The optimal cutoff values of SUVmax, MTV, and TLG for predicting overall survival (OS) after surgery were 3.88, 3.55 and 7.55, respectively. In multivariate analysis, each metabolic parameter influenced both OS and recurrence-free survival (RFS). TLG showed the lowest Akaike information criteria statistic value, indicating that it had the best ability to predict OS and RFS. High TLG was significantly associated with the number of lymph node metastases and poorly differentiated type. Patients with high TLG showed poorer RFS and OS, which were significantly worse than in those with low TLG. Tumor TLG predicted tumor malignancy potential and could be a useful prognostic predictor for extrahepatic bile duct carcinoma.

Detection of HER2 expression using 99mTc-NM-02 nanobody in patients with breast cancer: a non-randomized, non-blinded clinical trial

Background99mTc radiolabeled nanobody NM-02 (99mTc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between 99mTc-NM-02 uptake and HER2 expression in patients with breast cancer.MethodsThirty patients with pathologically confirmed breast cancer were recruited and imaged with both 99mTc-NM-02 SPECT/computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group (n = 24) and the treated group (n = 6). The maximal standard uptake value (SUVmax) of 18F-FDG and SUVmax and mean SUV (SUVmean) of 99mTc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression.ResultsNo meaningful relationship was observed between 18F-FDG uptake and HER2 expression in 30 patients with breast cancer. 99mTc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. 99mTc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. 99mTc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from 18F-FDG PET/CT. 99mTc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer.Conclusions99mTc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer.Trial registrationNCT04674722, Date of registration: December 19, 2020.

Altered structural and functional connectivity in Posterior Cortical Atrophy and Dementia with Lewy bodies

Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism.Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [18F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR.On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB.These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum.

The cingulate island sign in a mixed memory clinical cohort: Prevalence and diagnostic accuracy

IntroductionVisual rating of the cingulate island sign (CIS) on [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) has a high specificity for dementia with Lewy bodies (DLB) in selected cohorts such as DLB versus Alzheimer's disease (AD). In a mixed memory clinical population this study aimed to uncover the prevalence of CIS, the diagnostic accuracy for DLB, and the relationship between CIS and disease severity. MethodsCIS on [18F]FDG-PET was retrospectively assessed with the visual CIS rating scale (CISRs) in 1000 patients with a syndrome diagnosis of mild cognitive impairment (MCI) or dementia with no restrictions in etiological diagnosis. ResultsIn this cohort 24.3 % had a CISRs score ≥1 and 3.5 % had a CISRs score = 4. The prevalence of a CISRs score ≥1 was highest in DLB (74.0 %, n = 57). A CISRs score ≥1 was present in at least 9 % in other diagnostic groups. The prevalence of CIS across disease severities showed no statistically significant difference (p = 0.23). To differentiate DLB from non-DLB the optimal cut-off was a CISRs score ≥1 (balanced accuracy = 77.1 %) in MCI/mild dementia and a CISRs score ≥2 (balanced accuracy = 80.6 %) in moderate/severe dementia. The positive predictive value of a CISRs score = 4 for DLB was 57.7 % in MCI/mild dementia and 33.3 % in moderate/severe dementia. ConclusionThe CISRs is useful in differentiating DLB from other etiologies in a mixed memory clinical population. Balanced accuracy and positive predictive value may vary across disease severities in the population studied.