Standardized Uptake Ratio Research Articles

Population pharmacokinetic-pharmacodynamic analyses of amyloid positron emission tomography and plasma biomarkers for lecanemab in subjects with early Alzheimer's disease.

Lecanemab is a humanized immunoglobulin G1 monoclonal antibody that selectively binds to soluble Aβ aggregate species, while demonstrating low affinity for Aβ monomer. This article describes the population pharmacokinetic (PK) and PK/pharmacodynamic (PD) analyses for amyloid plaques, as measured using positron emission tomography (PET), and biomarkers of amyloid pathology as evidenced by Aβ42/40 ratio and plasma p-tau181 following i.v. administration of lecanemab in subjects with early Alzheimer's disease. Lecanemab PKs were well-characterized with a two-compartment model with first-order elimination. Final PK model contained covariate effects of anti-drug antibody positive status, sex, body weight, and albumin on clearance. The time course of amyloid PET standard uptake ratio (SUVr), plasma Aβ42/40 ratio, and p-tau181 were described using indirect response models with lecanemab exposure as a maximum effect function stimulating the reduction of SUVr, and as a linear function increasing Aβ42/40 ratio and decreasing p-tau181 formation rates. PK/PD simulations show that 10mg/kg biweekly dosing results in larger and faster decrease in SUVr and p-tau181 and increase in Aβ42/40 ratio as compared to 10mg/kg monthly dose. Furthermore, the PK/PD simulations showed that after treatment discontinuation the brain amyloid re-accumulation to baseline levels is slow with a recovery half-life of ~4 years, whereas plasma Aβ42/40 ratio and p-tau181 return to baseline levels faster than amyloid. Given the relationship between changes in amyloid PET SUVr and soluble biomarkers, the developed PK/PD models can be used to inform lecanemab dose regimens in future clinical studies.

18 F-NaF PET/CT in Presumed Aseptic Pseudarthrosis after Spinal Fusion: Correlation with Findings at Revision Surgery and Intraoperative Cultures.

Background Conventional imaging is useful to assess interbody fusion by showing complete trabecular bony bridging, but has a low positive predictive value for pseudarthrosis. Because alterations of bone metabolism may precede structural anatomical changes on computed tomography (CT), we aimed to investigate the ability of fluorine 18 sodium fluoride positron emission tomography/computed tomography ( 18 F-NaF PET/CT) to identify pseudarthrosis after spinal fusion using surgical revision as the reference standard. Methods We retrospectively reviewed 18 F-NaF PET/CT scans performed between February 2019 and September 2020 in patients experiencing pain after spinal fusion. We included the 18 patients who underwent revision surgery for suspicion of pseudarthrosis. Five consecutive patients who were clearly fused on CT served as the control group. Results In the revision surgery group ( n =18), visual assessment by 18 F-NaF PET/CT revealed that all 22 cages with an increased 18 F-NaF uptake around intercorporal fusion material had mobility at revision surgery, whereas none of the fused patients ( n =5) showed uptake around cage/intervertebral disk space. Among the 18 patients with presumed aseptic pseudarthrosis, intraoperative cultures revealed surgical site infection (SSI) caused by Cutibacterium acnes ( C. acnes ) in seven patients (38.9%). There was a statistically significant difference in standardized uptake values and uptake ratios between the revision surgery and control groups ( p =5.3× 10 -6 and p =0.0002, respectively). Conclusions 18 F-NaF PET/CT imaging appeared as a useful tool to identify pseudarthrosis following spinal fusion. The unexpectedly high prevalence (38.9%) of SSI caused by C. acnes found in presumed aseptic patients supports the utility of intraoperative cultures in revision cases for pseudarthrosis, even without preoperative clinical suspicion of SSI.

The role of metabolic tumor parameters predicting cervical lymph node metastasis in patients with head and neck squamous cell carcinoma.

This study aimed to investigate the contribution of metabolic positron emission tomography/computed tomography (PET/CT) parameters of the primary tumor in predicting regional lymph node metastasis (LNM) at initial staging in patients with head and neck squamous cell carcinoma (HNSCC). A total of 114 patients diagnosed with HNSCC and who underwent PET/CT scanning for staging were included in the study between May 2014 and December 2020. Predictive values of maximum standardized uptake value (SUVmax), maximum standardized uptake ratio (SURmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor in the prediction of cervical LNM were evaluated with logistic regression. The patients were diagnosed with cancer of the larynx (46.5%), oropharynx (9.6%), nasopharynx (22.8%), hypopharynx (4.4%), and oral cavity (16.7%). All metabolic parameters of the primary tumor were significantly different between patients with positive and negative LNM (all P < 0.001). MTV (P = 0.022) and TLG (P = 0.007) were significantly higher in patients with contralateral LNM. MTV value of the primary tumor was found as the single significant predictor of regional LNM in patients with HNSCC (OR = 23.17, P < 0.001 vs. OR = 31.1, P < 0.001, respectively) in univariate and multivariate logistic regression analyses. The sensitivity, specificity, and accuracy of MTV were 89%, 80%, and 86%, respectively. MTV of the primary tumor can predict regional LNM and guide the selection of the treatment modalities and clinical decisions in patients with HNSCC at initial staging.

Selective Serotonin Reuptake Inhibitor-Treatment Does Not Show Beneficial Effects on Cognition or Amyloid Burden in Cognitively Impaired and Cognitively Normal Subjects.

Preclinical studies indicate that selective serotonin reuptake inhibitors (SSRI) have beneficial effects on Alzheimer-related pathologies. Therefore, the aim of this study was to evaluate the influence of SSRI-treatment on amyloid burden in 18F-Florbetapir-positron emission tomography (PET) and on cognition in cognitively normal and cognitively impaired subjects. We included n = 755 cognitively impaired and n = 394 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) that underwent at least one 18F-Florbetapir-PET. Standardized uptake ratios (SUVR) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS) scores as well as follow-up results were compared between subgroups with a history of SSRI-treatment (SSRI+) and without SSRI-treatment (SSRI-) as well as in subgroups of SSRI+/Depression+ and SSRI+/Depression- and SSRI-/Depression+ and SSRI-/Depression-. 18F-Florbetapir-PET did not show significant differences of SUVR between the SSRI+ and SSRI- groups in both, cognitively impaired and cognitively normal participants. There were no differences in subgroups of SSRI+/Depression+ and SSRI+/Depression- and SSRI-/Depression+ and SSRI-/Depression-. However, SUVR showed a dose-dependent inverse correlation to the duration of medication in cognitively normal and in cognitively impaired patients. SRRI-treatment did not show an effect on ADAS scores. Furthermore, there was no effect on follow-up SUVR or on follow-up ADAS scores. Overall, SSRI-treatment did not show beneficial effects on amyloid load nor on cognition.

Using Deep Learning Radiomics to Distinguish Cognitively Normal Adults at Risk of Alzheimer's Disease From Normal Control: An Exploratory Study Based on Structural MRI.

ObjectivesWe proposed a novel deep learning radiomics (DLR) method to distinguish cognitively normal adults at risk of Alzheimer’s disease (AD) from normal control based on T1-weighted structural MRI images.MethodsIn this study, we selected MRI data from the Alzheimer’s Disease Neuroimaging Initiative Database (ADNI), which included 417 cognitively normal adults. These subjects were divided into 181 individuals at risk of Alzheimer’s disease (preAD group) and 236 normal control individuals (NC group) according to standard uptake ratio >1.18 calculated by amyloid Positron Emission Tomography (PET). We further divided the preaAD group into APOE+ and APOE− subgroups according to whether APOE ε4 was positive or not. All data sets were divided into one training/validation group and one independent test group. The proposed DLR method included three steps: (1) the pre-training of basic deep learning (DL) models, (2) the extraction, selection and fusion of DLR features, and (3) classification. The support vector machine (SVM) was used as the classifier. In the comparative experiments, we compared our proposed DLR method with three existing models: hippocampal model, clinical model, and traditional radiomics model. Ten-fold cross-validation was performed with 100 time repetitions.ResultsThe DLR method achieved the best classification performance between preAD and NC than other models with an accuracy of 89.85% ± 1.12%. In comparison, the accuracies of the other three models were 72.44% ± 1.37%, 82.00% ± 4.09% and 79.65% ± 2.21%. In addition, the DLR model also showed the best classification performance (85.45% ± 9.04% and 92.80% ± 2.61%) in the subgroup experiment.ConclusionThe results showed that the DLR method provided a potentially clinical value to distinguish preAD from NC.

11C-methionine PET/MRI in postoperative patients after craniotomy: zero echo time and head atlas versus CT-based attenuation correction.

Attenuation correction (AC) is an important topic in PET/MRI and particularly challenging after brain tumor surgery, near metal implants, adjacent bone and burr holes. In this study, we evaluated the performance of two MR-driven AC methods, zero-echo-time AC (ZTE-AC) and atlas-AC, in comparison to reference standard CT-AC in patients with surgically treated brain tumors at 11C-methionine PET/MRI. This retrospective study investigated seven postoperative patients with neuropathologically confirmed brain tumor at 11C-methionine PET/MRI. Three AC maps - ZTE-AC, atlas-AC and reference standard CT-AC - were generated for each patient. Standardized uptake values (SUV) were obtained at the metal implant, adjacent bone and burr hole. Standard uptake ratio (SUR) SURmetal/mirror, SURbone/mirror and SURburrhole/mirror were then calculated and analyzed with Bland-Altman, Pearson correlation and intraclass correlation reliability. Smaller mean percent bias range (Bland-Altman) was found for ZTE-AC than atlas-AC in all analyses (metal ZTE -0.46 to -0.02, metal atlas -3.57 to -3.26; bone ZTE -4.60 to -2.16, bone atlas -5.25 to -3.81; burr hole ZTE -0.95 to -0.52, burr hole atlas 7.86 to 8.87). Percent SD range (Bland-Altman) was large for both methods in all analyses, with lower absolute values for ZTE-AC (ZTE 7.02-8.49; atlas 11.47-14.83). A very strong correlation (Pearson correlation) was demonstrated for both methods compared to CT-AC (ZTE ρ 0.97-0.99, P<0.001; atlas ρ 0.88-0.91, P≤0.009) with higher absolute values for ZTE. An excellent intraclass correlation coefficient was found across all analyses for ZTE, atlas and CT maps (ICC ≥0.88). ZTE for MR-driven PET attenuation correction presented a more comparable performance to reference standard CT-AC at the postoperative site. ZTE-AC may serve as a useful diagnostic tool for MR-driven AC in patients with surgically treated brain tumors.

Impact of Partial Volume Correction on [18F]GE-180 PET Quantification in Subcortical Brain Regions of Patients with Corticobasal Syndrome.

Corticobasal syndrome (CBS) is a rare neurodegenerative condition characterized by four-repeat tau aggregation in the cortical and subcortical brain regions and accompanied by severe atrophy. The aim of this study was to evaluate partial volume effect correction (PVEC) in patients with CBS compared to a control cohort imaged with the 18-kDa translocator protein (TSPO) positron emission tomography (PET) tracer [18F]GE-180. Eighteen patients with CBS and 12 age- and sex-matched healthy controls underwent [18F]GE-180 PET. The cortical and subcortical regions were delineated by deep nuclei parcellation (DNP) of a 3D-T1 MRI. Region-specific subcortical volumes and standardized uptake values and ratios (SUV and SUVr) were extracted before and after region-based voxel-wise PVEC. Regional volumes were compared between patients with CBS and controls. The % group differences and effect sizes (CBS vs. controls) of uncorrected and PVE-corrected SUVr data were compared. Single-region positivity in patients with CBS was assessed by a >2 SD threshold vs. controls and compared between uncorrected and PVE-corrected data. Smaller regional volumes were detected in patients with CBS compared to controls in the right ventral striatum (p = 0.041), the left putamen (p = 0.005), the right putamen (p = 0.038) and the left pallidum (p = 0.015). After applying PVEC, the % group differences were distinctly higher, but the effect sizes of TSPO uptake were only slightly stronger due to the higher variance after PVEC. The single-region positivity of TSPO PET increased in patients with CBS after PVEC (100 vs. 83 regions). PVEC in the cortical and subcortical regions is valuable for TSPO imaging of patients with CBS, leading to the improved detection of elevated [18F]GE-180 uptake, although the effect sizes in the comparison against the controls did not improve strongly.

Risk analysis in peripheral clinical T1 non-small cell lung cancer correlations between tumor-to-blood standardized uptake ratio on 18F-FDG PET-CT and primary tumor pathological invasiveness: a real-world observational study.

Sublobar resection is not suitable for patients with pathological invasiveness [including lymph node metastasis (LNM), visceral pleural invasion (VPI), and lymphovascular invasion (LVI)] of peripheral clinical T1 (cT1) non-small cell lung cancer (NSCLC), while primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET-CT is related to pathological invasiveness, the significance differed among different institutions is still challenging. This study explored the relationship between the tumor-to-blood standardized uptake ratio (SUR) of 18F-FDG PET-CT and primary tumor pathological invasiveness in peripheral cT1 NSCLC patients. This retrospective study included 174 patients with suspected lung neoplasms who underwent preoperative 18F-FDG PET-CT. We compared the differences of the clinicopathological variables, metabolic and morphological parameters in the pathological invasiveness and less-invasiveness group. We performed a trend test for these parameters based on the tertiles of SUR. The relationship between SUR and pathological invasiveness was evaluated by univariate and multivariate logistics regression models (included unadjusted, simple adjusted, and fully adjusted models), odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. A smooth fitting curve between SUR and pathological invasiveness was produced by the generalized additive model (GAM). Thirty-eight point five percent of patients had pathological invasiveness and tended to have a higher SUR value than the less-invasiveness group [6.50 (4.82-11.16) vs. 4.12 (2.04-6.61), P<0.001]. The trend of SUVmax, mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), mean CT value (CTmean), size of the primary tumor, neuron-specific enolase (NSE), the incidence of LNM, adenocarcinoma (AC), and poor differentiation in the tertiles of SUR value were statistically significant (P were <0.001, <0.001, 0.010, <0.001, <0.001, 0.002, 0.033, <0.001, 0.002, and <0.001, respectively). Univariate analysis showed that the risk of pathological invasiveness increased significantly with increasing SUR [OR: 1.13 (95% CI: 1.06-1.21), P<0.001], and multivariate analysis demonstrated SUR, as a continuous variable, was still significantly related to pathological invasiveness [OR: 1.09 (95% CI: 1.01-1.18), P=0.032] after adjusting for confounding covariates. GAM revealed that SUR tended to be linearly and positively associated with pathological invasiveness and E-value analysis suggested robustness to unmeasured confounding. SUR is linearly and positively associated with primary tumor pathological invasiveness independent of confounding covariates in peripheral cT1 NSCLC patients and could be used as a supplementary risk maker to assess the risk of pathological invasiveness.

The imaging quantification of multiple organs by dynamic 18F-FDG PET/CT in discharged COVID-19 patients: A prospective pilot study.

Purpose: To early identify abnormal lesions by applying the 18F-FDG PET dynamic modeling approach for discharged patients recovering from COVID-19.Methods: Seven discharged COVID-19 patients (COVID-19 group), twelve healthy volunteers (control group 1), and eight cancer patients with normal pulmonary function (control group 2) were prospectively enrolled. Control group 1 completed static 18F-FDG PET/CT only; COVID-19 group and control group 2 completed 60-min dynamic 18F-FDG PET/CT. Among COVID-19 group and control group 2, the uptake of FDG on the last frame (at 55-60 min) of dynamic scans was used for static analysis. Prior to performing scans, COVID-19 patients provided negative real-time Reverse Transcription-Polymerase Chain Reaction (rRT-PCR) of SARS-CoV-2, normal lung functions test, and normal laboratory test. Organ-to-liver standard uptake ratio (OLR, i.e. SUVmaxevaluated organ/ SUVmaxliver) from conventional static data and Patlak analysis based on the dynamic modeling to calculate the 18F-FDG net uptake rate constant (Ki) were performed.Results: Compared to the control groups, COVID-19 patients at two to three months after discharge still maintained significantly higher Ki values in multiple organs (including lung, bone marrow, lymph nodes, myocardium and liver), although results for regular OLR measurements were normal for all discharged COVID-19 patients. Taking the image of lung as an example, the differences of SUVmax images between COVID-19 group and control group were hard to distinguish. In contrast, a high 18F-FDG signal of the lung among the COVID-19 group was observed for Ki images.Conclusion: The Ki from 18F-FDG PET/CT dynamic imaging quantification might contribute to identifying residual lesions for COVID-19 survivors.Trial registration: The trial is registered with ClinicalTrials.gov, number NCT04519255 (IRB-approved number, K52-1).

Influence of amyloid deposition on the interaction between tau and glucose metabolism

AbstractBackgroundPathological hallmarks of Alzheimer’s disease include the formation of extracellular Aβ plaques and intracellular neurofibrillary tau tangles, which with recent PET imaging advances can be assessed in vivo. Accumulation of tau has been closely linked to metabolic abnormalities in PET imaging studies, with inverse associations between tau deposition and glucose metabolism. This study aimed to assess whether the association between [18F]FDG and [18F]AV1451 in cognitively impaired patients is dependent on the presence of significant amyloid pathology.Method240 patients with mild cognitive impairment or Alzheimer’s disease (Mean age = 74.5 years, SD = 8.03) were evaluated from the Alzheimer’s Disease Neuroimaging Initiative (adni.loni.usc.edu). All participants completed a T1‐weighted MPRAGE MRI, amyloid ([18F]AV45 or [18F]florbetaben), [18F]AV1451 and [18F]FDG scans. Standard uptake ratio values were calculated in SPM12 to identify the glucose metabolic rate and tau deposition within cortical regions. Amyloid status (Aβ‐positive/Aβ‐negative) was determined from processed data using a whole brain cerebellar ratio with a cut‐off value of 1.11 ([18F]AV45) and 1.08 ([18F)florbetaben). Pearson’s correlation coefficients were calculated to assess the relationship between imaging modalities.ResultThere were significant negative associations between AV1451 and FDG tracer uptake in the medial temporal lobe (r = ‐0.389, p &lt;0 .001), occipital lobe (r = ‐0.276, p = 0.001), parietal lobe (r = ‐0.209, p = 0.014), and posterior cingulate (r = ‐0.245, p = 0.004) in Aβ‐positive patients. Similarly, a strong negative relationship was observed between the imaging modalities in Aβ‐negative patients in the medial temporal lobe (r = ‐0.345, p &lt; 0.001), however a significant positive association was also observed in the anterior cingulate cortex (r = 0.350, p &lt; 0.001).ConclusionThis study demonstrated that [18]FDG and [18F]AV1451 tracers have strong regional signal associations in patients with cognitive impairment. The results indicate that tau has a detrimental effect on glucose metabolism in the medial temporal lobe, independent of significant amyloid plaque formation. In patients determined as amyloid‐negative, we may be observing some compensatory regional increase in glucose metabolism in the early stages of tau accumulation.

Does [18F]FDG and [18F]AV1451 PET predict neurodegeneration?

AbstractBackground[18F]FDG PET is a well‐established and valuable biomarker in the assessment of neurodegenerative disorders, with high diagnostic utility, wide accessibility, and relatively low costs. Recent advances in PET imaging technology now allow for the in vivo exploration of tau deposition. However, it is still being debated which of [18F]FDG PET or [18F]AV1451 PET better predicts neurodegeneration. This study aimed to evaluate [18F]FDG PET and [18F]AV1451 PET imaging in predicting grey matter atrophy in patients with cognitive impairment.Method190 patients with mild cognitive impairment or Alzheimer’s disease (Mean age = 74.3 years, SD = 8.04) were evaluated from the Alzheimer’s Disease Neuroimaging Initiative (adni.loni.usc.edu). All participants completed a T1‐weighted MPRAGE MRI, [18F]AV1451 and [18F]FDG PET scans. Standard uptake ratio values were calculated in SPM12 to identify the glucose metabolic rate and tau deposition within the medial temporal lobe. Whole brain grey matter volumes were obtained from processed data from ADNI. Pearson’s correlation coefficients were calculated to assess the relationship between imaging modalities.ResultThere was a significant negative association between [18F]AV1451 uptake in the medial temporal lobe and whole brain grey matter volume (r = ‐0.288, p = 0.001). A stronger positive relationship was identified between medial temporal lobe [18F]FDG uptake and whole brain grey matter volume (r = 0.444, p &lt; 0.001).ConclusionThis study demonstrated that regional FDG and tau tracer uptake in patients with cognitive impairment both display a significant relationship with total grey matter volume. Whilst both tracers show utility in predicting a patient’s level of neurodegeneration, glucose metabolism as indicated by [18F]FDG PET appears to have a closer relationship to grey matter atrophy than PET markers of tau deposition.

Evaluating the relationship between soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and pathological substrates of Alzheimer’s disease (AD)

AbstractBackgroundDeveloping novel biomarkers of Alzheimer’s disease (AD) is critical for early disease detection and intervention. sTREM2 has proposed to be an early marker of glial activation. However, there has been significant controversy about the function of sTREM2. This study investigated the relationship between cerebral spinal fluid (CSF) sTREM2, and pathological changes in AD.MethodWe included patients with mild cognitive impairment, AD and healthy controls (n= 493, mean age= 73.7, SD= 6.1) were recruited for the Alzheimer’s Disease Neuroimaging Initiative. All participants completed a T1‐weighted MPRAGE MRI, amyloid ([18F]AV45 or [18F]Florbetaben), [18F]AV1451 and [18F]FDG scans. Standard uptake ratio values were calculated in SPM12 to identify the glucose metabolic rate and tau deposition within cortical regions. Amyloid status (Aβ positive/Aβ negative) was determined from processed data using a whole brain cerebellar ratio with a cut‐off value of 1.11. Correlations between CSF measurements, ROI, and voxel‐wise analyses were conducted using data from ADNI.ResultROI analyses demonstrated that increased CSF sTREM2 was associated with increased amyloid load in the whole brain, temporal, parietal, and occipital lobes of MCI patients. Additionally, increased CSF sTREM2 was associated with decreased glucose metabolism in the Posterior cingulate and parietal lobe in MCI patients. On the other hand, CSF sTREM2 was not significantly correlated with pathological changes in AD patients. However, voxel‐wise analysis comparing Aβ+ MCI patients to Aβ‐ CN subjects showed that increased CSF sTREM2 levels were associated with greater Aβ deposition in temporal and motor regions, increased grey matter volume in frontal and parietal regions, and decreased grey matter volume in the MT gyrus.ConclusionsTREM2 levels are associated with amyloid deposition in MCI patients but not in the late stage of AD patients, this suggest that glial activation is associated early on the disease.

Meta-GWAS of amyloid burden endophenotype combining PET and CSF results.

It is well known that Alzheimer's disease (AD) has a strong genetic component. Even though it is a highly heritable disease, a big fraction of AD heritability remains to be elucidated. Genetic analysis of endophenotypes tightly linked to the disease might help to identify or confirm AD genetic risk factors. GWAS results Amyloid β (Aβ42) in cerebrospinal fluid (CSF) or positron emission tomography (PET) measures were combined in a single meta-analysis. Six independent GWAS were run using a generalized linear model with four principal components and status as a covariate (PLINK software). The datasets had data for two different amyloid endophenotypes: CSF-Aβ42 levels from ADNI, Marqués de Valdecilla Hospital (Santander) and Fundació ACE (N= 1051); or PET-SUVR (amyloid global standardized uptake ratio) from ADNI and Fundació ACE (N= 607). GWAS results were meta-analysed using the sample size weighted method (METAL software). To reduce false positive findings, only genetic signals with opposite effect direction in PET and CSF endophenotypes were considered. Finally, we tried to replicate previously known genes for AD (de Rojas et al., MedRxiv 2019). After selecting SNPs with opposite effect on CSF and PET associations (N= 325051), we only observed genome wide significance in APOE locus (rs429358, P-value= 2.202×10-48) in the meta-GWAS. We also observed several suggestive signals in chromosomes 3, 5 and 6 (rs72977014, rs13164192 and rs4960198); further studies are needed to add evidence of AD association. Finally, relative to known AD genes we were able to replicate CR1 (rs4844610, P-value= 0.045) signal. By combining data from both β-amyloid endophenotypes (CSF and PET) we were able to replicate some well-known AD genes indicating that this approach could be a useful strategy to identify novel variants increasing the knowledge of AD genetic architecture.

The metabolic parameters based on volume in PET/CT are associated with clinicopathological N stage of colorectal cancer and can predict prognosis

BackgroundA combination of positron emission tomography and computed tomography (PET/CT) is an important modality for the diagnosis of carcinoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported as metabolic parameters in PET/CT since the late 1990s, and they are expected to be useful in diagnosing diverse cancers and as prognostic biomarkers. We evaluated the potential of these parameters in the prognosis of colorectal cancer (CRC) by comparing them with conventional parameters, including the maximum standardized uptake value (SUVmax). We enrolled 84 patients who underwent surgery for CRC without distal metastasis between April 2015 and April 2019. SUVmax, MTV, and TLG were measured by 18F-fluorodeoxyglucose (FDG)-PET/CT. To find an optimal threshold value related to prognosis, the volume of interest in the primary carcinoma was measured at fixed relative and absolute thresholds based on SUVmax (30%, 40%, and 50%; 2.5, 3.0, and 3.5, respectively), tumor-to-liver standardized uptake ratios, TLR (1.0, 1.5, and 2.0), and SUV normalized to lean body mass, SUL (2.0, 2.5, and 3.0). After classifying the patients into two groups according to pathological N stage, the optimal threshold values of all metabolic parameters were compared between groups using a non-parametric comparison test.ResultThe most suitable thresholds for MTV were a SUVmax of 3.5 and a TLR 2.0. TLG with a SUVmax value of 40% showed the most significant difference. The MTV standard uptake ratio of 2.0 was significantly associated with pathological N stage.ConclusionOur results suggest that an MTV TLR 2.0 on PET/CT reflects pathological N stage in local patients with CRC.

Parametric mapping for 11C-metomidate PET-computed tomography imaging in the study of primary aldosteronism.

11C-metomidate (11C-MTO) PET-computed tomography (CT) imaging has shown good sensitivity and specificity for the classification of bilateral or unilateral overexpression of aldosterone. This work seeks to investigate the usefulness of parametric maps via kinetic modeling of 11C-metomidate data into the clinical diagnosis pathway. Twenty-five patients were injected with 172 ± 12 MBq of 11C-metomidate and a dynamic PET scan performed of the adrenal glands. A blood time-activity curve was drawn from a volume of interest in the left ventricle and converted to a plasma time-activity curve. Metabolite correction was performed with a population-based correction. We performed regional-based graphical Patlak analysis to calculate the regional uptake rate constant Ki(REG), and also calculated parametric maps of Ki(VOX) using a voxel-based technique. Comparison of Ki(REG), and the maximum lesion voxel from parametric maps Ki(mVOX) demonstrated a high correlation for all subjects (r2 = 0.96). Ki(mVOX) allowed differentiation between cases of active and inactive unilateral adenoma when compared to bilateral hyperplasia (P < 0.017), a feature not observed with standardized uptake ratios (SUVmax) analysis. Ki(mVOX) demonstrated a poor correlation of 0.68 with SUVmax, indicating the differences through the use of static and dynamic imaging. Three false-negative cases based on SUV analysis indicated that Ki(mVOX) was able to successfully differentiate the clinical presentation for these cases. Our work demonstrates that parametric Ki(VOX) was able to successfully differentiate between patients with bilateral hyperplasia and patients with unilateral adrenal adenoma in our cohort and that Ki may be considered be an additional useful metric to SUV in 11C-metomidate PET-CT imaging.

Conventional to Early Phase Standardized Uptake Value Ratio on 18F FDG PET/CT Could Reflect Prognosis in Patients with Non-small Cell Lung Cancer

Objective: A high metabolism/perfusion rate in the tumor is known to be factor indicating poor prognosis. The goal of this study was to investigate the prognostic value of the ratio of the conventional standard uptake value to early-phase imaging standard uptake value in patients with newly diagnosed non-small cell lung cancer.&#x0D; Materials and Methods: Early-phase imaging was obtained in the first 120 seconds and conventional imaging was taken after median 66 minutes. The ratio of the conventional standard uptake value to early-phase imaging standard uptake value was calculated. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to assess the relationship between progression-free survival and ratio of the conventional standard uptake value to early-phase imaging standard uptake.&#x0D; Results: A total of 77 patients with non-small cell lung cancer were recruited. Progression-free survival analysis was performed in 52 inoperable patients. Progression-free survival was found to be related to conventional standard uptake value (p&lt;0.001), tumor size (p&lt;0.001) and ratio of the conventional standard uptake value to early-phase imaging standard uptake in univariate analysis (p=0.047). In the multivariate analysis, ratio of the conventional standard uptake value to early-phase imaging standard uptake (p=0.001, HR=1.145, 95CI%:1.145-1.719) and tumor size (p&lt;0.001, HR=1.026, 95CI%:1.007-1.045) were found to be independent poor prognostic factors.&#x0D; Conclusion: The ratio of the conventional standard uptake value to early-phase imaging standard uptake was found an indicator for prognosis. Evaluating the early phase imaging, without a need for kinetic program or software, without disrupting the routine functioning of the clinic, with conventional imaging may contribute to cancer patient management. There is a need for studies with larger groups of patients.

Clinical Utility of 18 F-APN-1607 Tau PET Imaging in Patients with Progressive Supranuclear Palsy.

18 F-APN-1607 is a novel tau PET tracer characterized by high binding affinity for 3- and 4-repeat tau deposits. Whether 18 F-APN-1607 PET imaging is clinically useful in PSP remains unclear. The objective of this study was to investigate the clinical utility of 18 F-APN-1607 PET in the diagnosis, differential diagnosis, and assessment of disease severity in patients with PSP. We enrolled 3 groups consisting of patients with PSP (n=20), patients with α-synucleinopathies (MSA with predominant parkinsonism, n=7; PD, n=10), and age- and sex-matched healthy controls (n=13). The binding patterns of 18 F-APN-1607 in PET/CT imaging were investigated. Regional standardized uptake ratios were compared across groups and examined in relation to their utility in the differential diagnosis of PSP versus α-synucleinopathies. Finally, the relationships between clinical severity scores and 18 F-APN-1607 uptake were investigated after adjustment for age, sex, and disease duration. Compared with healthy controls, patients with PSP showed increased 18 F-APN-1607 binding in several subcortical regions, including the striatum, putamen, globus pallidus, thalamus, subthalamic nucleus, midbrain, tegmentum, substantia nigra, pontine base, red nucleus, raphe nuclei, and locus coeruleus. We identified specific regions that were capable of distinguishing PSP from α-synucleinopathies. The severity of PSP was positively correlated with the amount of 18 F-APN-1607 uptake in the subthalamic nucleus, midbrain, substantia nigra, red nucleus, pontine base, and raphe nuclei. 18 F-APN-1607 PET imaging holds promise for the diagnosis, differential diagnosis, and assessment of disease severity in patients with PSP. © 2021 International Parkinson and Movement Disorder Society.

Evaluation of 18F‐MK‐6240 and 18F‐AV‐1451 tau PET tracers in Alzheimer disease

AbstractBackgroundTwo tau tracers, 18F‐MK‐6240 and 18F‐AV‐1451, have recently been introduced into many studies of Alzheimer disease (AD) but it remains unclear how each tracer evaluates heterogenous tau pathology. In this study we compared the binding of two tau‐specific PET tracers in asymptomatic control (AC) and (AD) participants enrolled in DIAN.MethodNine AC and three AD participants were recruited from DIAN underwent PET/CT imaging twice, one with 18F‐MK‐6240 and the other one with 18F‐AV‐1451 on consecutive days. AC participants were scanned with full dynamic scan (0‐110 min for 18F‐MK‐6240 and 0‐105 min for 18F‐AV‐1451) while 20 min (90‐110 for 18F‐MK‐6240 and 80‐100 min for 18F‐AV‐1451) scan for AD participants. Data were analysed using standardized uptake ratios (SUVr) with whole cerebellum used as a reference tissue from an early frame duration (SUVr0.75‐2.5 min) for all nine AC participants and late SUVr (SUVr20min) for all twelve participants. In addition, centrum semiovale was tested as reference region for SUVr20min. Relative delivery (R1) and distribution volume ratio (DVR = BPND+1) were generated using SRTM2 methods from nine AC dynamic data with cerebellum as reference. Bland–Altman analyses were used to evaluate an agreement between two tracers both for AC and AD participants.ResultBoth tracers show an agreement for relative flow and binding in AC participants as shown in Figure 1. In AD participants, 18F‐MK‐6240 shows a proportionally higher tracer specific binding compare to 18F‐AV‐1451 for regions with an average SUVr value higher than 1.5 as seen in Figure 2. 18F‐MK‐6240 shows relatively lower uptake compared to 18F‐AV‐1451 in AC and significantly higher in AD as in Figure 3. The SUVr attain stable after 80 min post injection for both tracers, but the centrum semiovale reference tissue‐based SUVr shows higher contrast between both tracers than the ones using cerebellum reference tissue (Fig 4).ConclusionBoth tracers show an agreement in AC participants. 18F‐MK‐6240 demonstrates higher SUVr compared to 18F‐AV‐1451 for participants with significant tau deposition in AD. Centrum semiovale is suggested for reference region for both tracers and will be evaluated carefully by the ongoing evaluation study.

KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver

BackgroundDeriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM).Methods2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student’s t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis.These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively.ResultsFifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student’s t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85.ConclusionThe correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

Effects of Hyperthyroidism on Adipose Tissue Activity and Distribution in Adults.

Background: Positron emission tomography (PET) has provided evidence that adult humans retain metabolically active brown adipose tissue (BAT) depots. Thyroid hormones (TH) stimulate BAT thermogenesis by central and peripheral mechanisms. However, the effect of hyperthyroidism on BAT activity and BAT volume in humans is yet not fully understood. The aim of this study was to investigate the effect of TH on (i) the metabolic activity of brown and white adipose tissue (WAT) depots, (ii) on abdominal visceral and subcutaneous adipose tissue area, and (iii) on serum levels of metabolically active cytokines. Methods: Nineteen patients with overt hyperthyroidism were investigated through repeated 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in the hyperthyroid and in the euthyroid state. The 2-[18F]FDG uptake was calculated as standard uptake ratio with blood pool as reference. Fat areas were quantified by means of CT segmentation. Serum levels of fetuin A and B, fibroblast growth factor 21, adipocyte fatty acid-binding protein (AFABP), retinol-binding protein 4, pro-enkephalin, pro-neurotensin, and neuregulin 4 were determined in the hyperthyroid and in the euthyroid state for each subject. Results: 2-[18F]FDG uptake was increased in the hyperthyroid state in BAT in comparison with the euthyroid phase (p = 0.001). There was no correlation between serum free triiodothyronine (fT3) and free thyroxine (fT4) levels and 2-[18F]FDG uptake in BAT or WAT. In the hyperthyroid state, fT3 levels were positively associated with skeletal muscle standardized uptake value ratios. Areas of visceral adipose tissue and skeletal muscle were significantly decreased in hyperthyroidism. AFABP levels correlated positively with fT3 (p = 0.031, β = 0.28) and fT4 (p = 0.037, β = 0.27) in the hyperthyroid state. Conclusions: Our results suggest that the contribution of increased TH levels to the glucose uptake of BAT and WAT is low compared with that of the skeletal muscle. Hyperthyroid subjects have reduced areas of visceral adipose tissue and increased AFABP levels.