Plasma Core Alzheimer's Disease Biomarkers Predict Amyloid Deposition Burden by Positron Emission Tomography in Chinese Individuals with Cognitive Decline.

Blood-based biomarkers have been considered as a promising method for the diagnosis of Alzheimer's disease (AD). The reliability and accuracy of plasma core AD biomarkers, including phosphorylated tau (P-tau181), total tau (T-tau), Aß42, and Aß40, have also been confirmed in diagnosing AD and predicting cerebral ß-amyloid (Aß) deposition in Western populations, while fewer research studies have ever been conducted in China's Han population. In this study, we investigated the capability of plasma core AD biomarkers in predicting cerebral Aß deposition burden among the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort consisting of cognitively normal (CN), mild cognitive impairment (MCI), AD dementia, and non-Alzheimer's dementia disease (Non-ADD). Body fluid (plasma and CSF) AD core biomarkers were measured via single-molecule array (Simoa) immunoassay. The global standard uptake value ratio (SUVR) was then calculated by 18F-florbetapir PET, which was divided into positive (+) and negative (-). The most significant correlation between plasma and CSF was plasma P-tau181 (r = 0.526, P < 0.0001). Plasma P-tau181 and P-tau181/T-tau ratio were positively correlated with global SUVR (r = 0.257, P < 0.0001; r = 0.263, P < 0.0001, respectively), while Aß42 and Aß42/Aß40 ratio were negatively correlated with global SUVR (r = -0.346, P < 0.0001; r = -0.407, P < 0.0001, respectively). Interestingly, voxel-wise analysis showed that plasma P-tau181 and P-tau181/T-tau ratio were negatively related to 18F-florbetapir PET in the hippocampus and parahippocampal cortex. The optimal predictive capability in distinguishing all Aß+ participants from Aß- participants and MCI+ from MCI- subgroups was the plasma P-tau181/T-tau ratio (AUC = 0.825 and 0.834, respectively). Our study suggested that plasma P-tau181 and P-tau181/T-tau ratio possessed better diagnostic and predictive values than plasma Aß42 and Aß42/Aß40 in this cohort, a finding that may be useful in clinical practices and trials in China.

Prediction value of 18F-FDG PET/CT intratumor metabolic heterogeneity parameters for recurrence after radical surgery of stage II/III colorectal cancer.

Purpose: We explored the predictive effect of intratumor metabolic heterogeneity indices extracted from 18F-FDG PET/CT on recurrence in stage II/III colorectal cancer after radical surgery. Methods: A total of 140 stage II/III colorectal cancer patients who received preoperative 18F-FDG PET/CT and radical resection were enrolled. 18F-FDG traditional parameters including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) under different thresholds; heterogeneity indices including the coefficient of variation with SUV 2.5 as a threshold (CV2.5), CV40%, heterogeneity index-1 (HI-1) calculated by the fixed-threshold method, and HI-2 calculated by the percentage threshold method; and clinicopathological information were collected. We concluded that relationships exist between these data and patients' disease-free survival (DFS). Results: Regional lymph node status (P < 0.001), nerve invasion (P = 0.036), tumor thrombus (P = 0.005), and HI-1 (P = 0.010) exhibited significant differences between the relapse and non-relapse groups, while SUVmax, MTV2.5, MTV40%, TLG2.5, TLG40%, CV2.5, CV40%, HI-2, and other clinicopathological factors had no differences between the relapse and non-relapse groups. Multivariate analysis demonstrated that HI-1 (HR = 1.02, 1.00-1.04, P = 0.038), regional lymph node metastasis (HR = 2.95, 1.37-6.38, P = 0.006), and tumor thrombus status (HR = 2.37, 1.13-4.99, P = 0.022) were independent factors significantly related to DFS. Conclusion: HI-1, tumor thrombus status, and regional lymph node status could predict the recurrence of stage II/III colorectal cancer after radical resection and had an advantage over other 18F-FDG PET/CT conventional parameters and heterogeneity indices.

Correlation between Cerebrospinal Fluid Core Alzheimer's Disease Biomarkers and ß-Amyloid PET in Chinese Dementia Population.

The current diagnoses of Alzheimer's disease (AD) mainly rely on such measures as amyloid-ß (Aß) and tau neuropathology biomarkers in vivo via cerebrospinal fluid (CSF) and positron emission tomography (PET) imaging, which had been systematically studied in Caucasian individuals, whereas diagnostic performances of these approaches in Chinese dementia population still remain unclear. This study investigated the associations between the levels of CSF core AD biomarkers, including phosphorylated tau (p-Tau181), total tau (t-Tau), Aß42, and Aß40 measured by the single-molecule array (Simoa) and cerebral Aß deposition status assessed by 18F-Florbetapir PET (Aß PET), and evaluated the predictive values of CSF core AD biomarkers in discriminating Aß PET status in a clinical dementia cohort of the Chinese population, which consisted of patients with mild cognitive impairment (MCI), AD dementia, and non-Alzheimer's dementia disease (Non-ADD). Global standard uptake value ratios (SUVRs) were calculated by Aß PET, which was divided into positive (Aß+) and negative (Aß-) through visual analysis. CSF p-Tau181 and p-Tau181/t-Tau ratio were positively correlated with the global SUVR, while CSF Aß42 and Aß42/Aß40 ratio were negatively correlated with the global SUVR. CSF Aß40 has the highest predictive value in discriminating the MCI group from the AD group, while CSF p-Tau181 was applied to discriminate the AD group from the non-ADD group. CSF Aß42/Aß40 ratio, as the optimal predictive factor, was combined with APOE ε4 status rather than age and education, which could improve the predictive ability in differentiating the Aß+ group from the Aß- group. The results reveal the universal applicability of CSF core AD biomarkers and Aß PET imaging in Chinese dementia population, which is helpful in clinical practice and drug trials in China.

Efficient and automatic synthesis of TSPO PET ligand [18F]-GE-180 and its application in rheumatoid arthritis model.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic synovial inflammation, which ultimately leads to joint deformity and dysfunction. [18F]-GE-180 is a specific PET tracer of the 18 kDa translocator protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of inflammation. Our study addresses the need to streamline the automatic synthesis of [18F]-GE-180 to make it more accessible for routine production and widespread clinical evaluation and application. The nucleophilic radiofluorination was performed on an AllinOne synthesis module by SPE purification method, and the formulated [18F]-GE-180 was obtained in non-decay corrected radiochemical yields of 69 ± 1.8% in 32 min. PET/CT imaging in animal model showed that [18F]-GE-180 highly concentrated in joints from RA rats. This methodology facilitates efficient synthesis of [18F]-GE-180 in a commercially available synthesis module and shows potential diagnosis performance in RA models.

Correlation between 18F-FDG PET/CT intra-tumor metabolic heterogeneity parameters and KRAS mutation in colorectal cancer.

PURPOSE: The study aimed to evaluate the relationship between intra-tumor metabolic heterogeneity parameters of 18F-FDG and KRAS mutation status in colorectal cancer (CRC) patients and which threshold heterogeneity parameters could better reflect the heterogeneity characteristics of colorectal cancer. METHODS: Medical data of 101 CRC patients who underwent 18F-FDG PET/CT and KRAS mutation analysis were selected. On PET scans, 18F-FDG traditional indices maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity parameters coefficient of variation with a threshold of 2.5 (CV2.5), CV40%, heterogeneity index-1 (HI-1), and HI-2 of the primary lesions were obtained. We inferred correlations between these 18F-FDG parameters and KRAS mutation status. RESULTS: 41 patients (40.6%) had KRAS gene mutation. Assessment of FDG parameters showed that SUVmax (19.00 vs. 13.16, p < 0.001), MTV (11.64 vs. 8.83, p = 0.001), and TLG (102.85 vs. 69.76, p < 0.001), CV2.5 (0.55 vs. 0.46, p = 0.006), and HI-2 (14.03 vs. 7.59, p < 0.001) of KRAS mutation were higher compared to wild-type (WT) KRAS. CV40% (0.22 vs. 0.24, p = 0.001) was lower in the KRAS mutation group, while HI-1 had no significant difference between the two groups. Multivariate analysis showed that MTV (OR = 4.97, 1.04-23.83, p = 0.045) was the only significant predictor in KRAS mutation, using a cut-off of 7.62 (AUC = 0.695), and MTV showed a sensitivity of 90.2% and specificity of 45.0%. However, the PET parameters were not independent predictors in KRAS mutation. CONCLUSION: KRAS gene mutant CRC patients had more 18F-FDG uptake (SUVmax, MTV, TLG) and heterogeneity (CV2.5, HI-2) than WT KRAS. MTV was the only independent predictor of KRAS gene mutation in colorectal cancer patients.

[Value of 18F-FDG PET/CT Imaging in Secondary Extramedullary Infiltration of Multiple Myeloma].

OBJECTIVE: To investigate the characteristics of 18F-FDG PET/CT images of multiple myeloma secondary extramedullary infiltration in order to improve recognition. METHODS: Twenty-one patients with multiple myeloma secondary extramedullary infiltration confirmed by pathology or follow-up from January 2012 to October 2020 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. All the patients underwent 18F-FDG PET/CT imaging before treatment, and the PET/CT characteristics of extramedullary infiltration and bone marrow were analyzed. RESULTS: Twenty-one patients included 12 males and 9 females, aged from 41 to 77 years old, with an average of 58.3±10.0; 9 cases of extramedullary infiltration involving lymph nodes; lung, stomach, spleen, and kidney were involved respectively in 2 cases; retroperitoneal, right auricle, subcutaneous nodule, and spinal meninges involvement were reported in each one case respectively. The maximum SUVmax value of extra-medullary lesions was 21.2, the minimum value was 2.1, and mean was 7.7±5.3. The maximum SUVmax value of bone marrow was 33.5, the minimum was 2.4, and mean was 6.6±3.6. There was no statistically significant difference in SUVmax value between extra-medullary lesions and bone marrow (Z=-1.195, P=0.232). CONCLUSION: 18F-FDG PET/CT not only has a good diagnostic value for multiple myeloma, but also a good evaluation value for secondary extramedullary infiltration, which provides reference for clinical treatment and prognosis.

Prognostic Value of Intratumor Metabolic Heterogeneity Parameters on 18F-FDG PET/CT for Patients with Colorectal Cancer.

Purpose: Intratumor metabolic heterogeneity parameters on 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) have been proven to be predictors of the clinical prognosis of cancer patients. The study aimed to examine the correlation between 18F-FDG PET-CT-defined heterogeneity parameters and the prognostic significance in patients with colorectal cancer. Methods: The study included 188 patients with colorectal cancer who received surgery and 18F-FDG PET/CT examinations. Preoperative 18F-FDG PET/CT conventional and metabolic heterogeneity parameters were collected, including maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), heterogeneity index-1 (HI-1) and heterogeneity index-2 (HI-2), and clinicopathological information. Correlations between these parameters and patient survival outcomes were inferred. Results: The associations between 18F-FDG PET/CT parameters and clinical outcomes were analyzed. Tumor thrombus (P < 0.001), tumor stage (P=0.001), MTV (P=0.003), HI-1 (P=0.032), and HI-2 (P=0.001) differed between the two groups with and without recurrence. Multivariate analysis showed that, in the radical surgery group, HI-2 (HR = 1.10, 95% CI: 1.04-1.17, P=0.001), tumor stage (HR = 20.65, 95% CI: 4.81-88.62, P < 0.001), and regional lymph nodes status (HR = 0.16, 95% CI: 0.04-0.57, P=0.005) were independent variables significantly correlated with progression-free survival (PFS) and HI-2 (HR = 1.16, 95% CI: 1.07-1.26, P < 0.001) was an independent variable affecting overall survival (OS). In the palliative surgery group, HI-2 (HR = 1.03, 95% CI: 1.01-1.06, P=0.020) was an independent variable affecting PFS, and all the parameters were not statistically significant for OS. Conclusion: HI-2, tumor stage, and regional lymph nodes status might predict the outcomes of colorectal cancer more effectively than other 18F-FDG PET/CT defined parameters.

An automated radiosynthesis of (S)-[18F]28 for PET imaging of Alzheimer's disease.

18F-labeled 2-arylbenzoxazole derivative (S)-[18F]28 is potent and selective radiopharmaceutical Aß tracers for Alzheimer's disease positron-emission tomography (PET). Our study aimed to enable facile preparation of (S)-[18F]28 in commercially available PET tracer production facilities to promote the widespread application and clinical translation. Here, we successfully demonstrated an automated radiosynthesis of (S)-[18F]28 with high radiochemical yield and radiochemical purity by the AllinOne radiosynthesis module. The method developed here can facilitate extensive use of (S)-[18F]28 in large-scale clinical trials.

Primary pulmonary artery sarcoma with intrapulmonary metastases based on PET/CT imaging: a case report and literature review.

Primary pulmonary artery sarcoma is an extremely rare and highly aggressive malignant tumor of cardiovascular system. It is usually misdiagnosed as pulmonary thromboembolism due to its atypical clinical features and similar clinical symptoms. Different from published reports, our case received both enhanced CT and 18F-FDG PET/CT examination before the pathologic result, and lung metastases had already occurred at the time of diagnosis. We herein reported a case of 41-year-old female patient who suffered from cough and chest tightness for more than a month. Laboratory examination indicated that both blood routine and tumor markers were within the normal range, and only the D-dimer slightly elevated. Contrast-enhanced chest computed tomography showed right pulmonary artery lesion and multiple nodular located right upper lung, the lesion was mild heterogeneous enhancement. No obvious abnormalities were found in deep vein of bilateral lower extremities on ultrasonography. In order to confirm the nature of these lesions, PET/CT scan was performed, which revealed stripe hypermetabolism in right pulmonary artery and nodular hypermetabolism in right upper lung, and the rest of the whole-body PET imaging were negative, a diagnosis of primary pulmonary artery malignancy with pulmonary metastases was made, and pulmonary thromboembolism was ruled out. Biopsy of right pulmonary lesions was performed and histopathological examination indicated pulmonary artery sarcoma. She only received palliative conservative medical treatment because the disease was late stage according to the tumor-node-metastasis (TNM) staging system, and did not acceptable surgical treatment, and was in good health during recent follow-up. Our study suggested that 18F-FDG PET/CT image is a good approach for the diagnosis of pulmonary artery sarcoma and could provide adjunct value for further treatment.

Imaging features of glucagonoma syndrome: A case report and review of the literature.

Glucagonoma syndrome appears as an extremely rare neuroendocrine tumour, with few studies ever having detailed its imaging manifestations. In particular, the magnetic resonance imaging (MRI) features of the lesion have not yet been reported. The present study describes a 54-year-old male who presented with uncontrollable skin erythema and weight loss that had been apparent for two years, and diabetes mellitus that had been apparent for five years. The glucagon level was 180 pg/ml. The plain abdominal computed tomography (CT) scan revealed a solid tumour in the neck of the pancreas, which was slightly reinforced during the arterial phase of the enhanced CT scan. Upon MRI, the lesion exhibited a low signal on T1-weighted imaging, and a slightly high signal on T2-weighted and half-Fourier acquisition single-shot turbo spin echo sequence imaging, which measured ~4.5×3.0×3.0 cm in size. Upon diffusion-weighted imaging, the lesion demonstrated heterogeneous hyperintensity, which was mildly enhanced during the arterial phase and washed out during the portal venous phase of gadopentetate dimeglumine-enhanced MRI. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET)-CT identified a mild uptake of 18F-FDG by the lesion. The patient was diagnosed with glucagonoma syndrome, and a distal pancreatectomy and splenectomy were subsequently performed. Microscopy revealed that the tumour cells exhibited nest- and belt-like arrangements. The immunohistochemical staining identified positive reactions for glucagon, synaptophysin and chromogranin A, which are consistent with a diagnosis of glucagonoma. Following surgery, the symptoms disappeared and the glucagon level returned to normal. In conclusion, imaging examinations are useful for determining the location and size of a glucagonoma. In particular, MRI is able to identify the distinctive morphological features of the lesion. Immunohistochemical staining provides diagnostic evidence based upon the neuroendocrine features.

Positron emission tomography/computed tomography imaging and rheumatoid arthritis.

Rheumatoid arthritis (RA) is a phenotypically heterogeneous, chronic, destructive inflammatory disease of the synovial joints. A number of imaging tools are currently available for evaluation of inflammatory conditions. By targeting the upgraded glucose uptake of infiltrating granulocytes and tissue macrophages, positron emission tomography/computed tomography with fluorine-18 fluorodeoxyglucose ((18) F-FDG PET/CT) is available to delineate inflammation with high sensitivity. Recently, several studies have indicated that FDG uptake in affected joints reflects the disease activity of RA. In addition, usage of FDG PET for the sensitive detection and monitoring of the response to treatment has been reported. Combined FDG PET/CT enables the detailed assessment of disease in large joints throughout the whole body. These unique capabilities of FDG PET/CT imaging are also able to detect RA-complicated diseases. Therefore, PET/CT has become an excellent ancillary tool to assess disease activity and prognosis in RA.

Positron emission tomography/computerized tomography in the evaluation of primary non-Hodgkin's lymphoma of prostate.

Primary malignant lymphoma of the prostate is exceedingly rare. Here we report a case of a 65-year-old man who presented with increased urinary frequency, urinary urgency, and urinary incontinence for two years. Benign prostatic hypertrophy was suspected at primary impression. Ultrasound revealed a hypoechoic lesion of the prostate. The total serum prostate-specific antigen was within normal range. Positron emission tomography/computerized tomography (PET/CT) showed a hypermetabolic prostatic lesion. Prostate biopsy was consistent with a non-germinal center diffuse large B cell lymphoma. There was complete remission of the prostatic lesion following six cycles of chemotherapy as shown on the second PET/CT imaging. ¹8F-fluoro-deoxy glucose PET/CT is not only a complement to conventional imaging, but also plays a significant role in the diagnosis and evaluation of treatment response of prostatic lymphoma.

Association of MIF-173G/C and MBL2 codon 54 gene polymorphisms with rheumatoid arthritis: a meta-analysis.

The aim of this study was to evaluate the association between macrophage migration inhibitory factor (MIF) -173G/C (rs755622), mannose-binding lectin (MBL2) exon 1 codon 54 (rs1800450) gene polymorphisms and rheumatoid arthritis (RA) susceptibility in ethnically different populations. A meta-analysis was conducted (allelic contrast, the additive model, the dominant model and the recessive model) on the MIF-173G/C polymorphism across five studies (four European and one Asian studies), and the MBL2 codon 54 polymorphism with five studies (four Asian and one European studies), respectively. Meta-analysis indicated an association between the MIF-173G/C in all study subjects in allelic contrast (OR=1.19, 95%CI: 1.05-1.35, P=0.001), the additive model (OR=1.68, 95CI: 1.13-2.49, P=0.001), the dominant model (OR=1.17, 95CI: 1.01-1.35, P=0.003), the recessive model (OR=1.63, 95CI: 1.10-2.42, P=0.001). While stratified by ethnicity with European populations, an association was found in allelic contrast (OR=1.20, 95CI: 1.04-1.38, P=0.002), the additive model (OR=1.85, 95CI: 1.19-2.88, P=0.001), the dominant model (OR=1.20, 95CI: 1.02-1.41, P=0.003). With respect to MBL2 codon 54 polymorphism and RA, no association was found in all study subjects in all comparisons, but there was an association while stratified by ethnicity with Asian populations in the dominant model (OR=1.50, 95CI: 1.01-2.23, P=0.007). In conclusion, the present study suggests that the MIF-173G/C polymorphism is associated with RA susceptibility, but the MBL2 codon 54 polymorphism is not associated with RA.