Metabolic activity via 18F-FDG PET/CT is predictive of microsatellite instability status in colorectal cancer.

PURPOSE: Identification of microsatellite instability high (MSI-H) colorectal cancer (CRC) is crucial for screening patients most likely to benefit from immunotherapy. We aim to investigate whether the metabolic characteristics is related to MSI status and can be used to predict the MSI-H CRC. METHODS: A retrospective analysis was conducted on 420 CRC patients who were identified via [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography(CT) prior to therapy. Maximum standardized uptake (SUVmax), mean standardized uptake (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary tumor were calculated and compared between MSI-H and microsatellite stability (MSS). Predictive factors of MSI status were selected from metabolic parameters and clinicopathological profiles via a multivariate analysis. RESULTS: Of 420 colorectal cancers, 44 exhibited a high incidence of MSI. Both MTV and TLG were significantly higher in MSI-H group compared with the MSS group (P = 0.004 and P = 0.010, respectively). Logistic regression analysis indicated that CRC with MSI-H were related to younger age (P = 0.013), primary lesion located at right hemi-colon (P < 0.001) and larger MTV on PET/CT imaging (P = 0.019). MTV more than 32.19 of colorectal cancer was linked to the presence of MSI (P = 0.019). CONCLUSION: Tumor metabolic burden were higher in MSI-H CRC which may be useful for predicting the MSI status of CRC patient and thus aid in determination of immunotherapy for patients with CRC.

A novel prognostic index for diffuse large B-cell lymphoma combined baseline metabolic tumour volume with clinical and pathological risk factors.

OBJECTIVES: This study aimed to develop a novel prognostic index integrating baseline metabolic tumour volume (MTV) along with clinical and pathological parameters for diffuse large B-cell lymphoma (DLBCL). METHODS: This prospective trial enrolled 289 patients with newly diagnosed DLBCL. The predictive value of novel prognostic index was compared with Ann Arbor staging and National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI). We used the concordance index (C-index) and a calibration curve to determine its predictive capacity. RESULTS: Multivariate analysis revealed high MTV (>191 cm 3 ), Ann Arbor stage (III-IV) and MYC/BCL2 double expression lymphoma (DEL) to be independently associated with inferior progression-free survival (PFS) and overall survival (OS). Ann Arbor stage and DEL could be stratified by MTV. Our index, combining MTV with Ann Arbor stage and DEL status, identified four prognostic groups: group 1 (no risk factors,), group 2 (one risk factor), group 3 (two risk factors), and group 4 (three risk factors). The 2-year PFS rates were 85.5, 73.9, 53.6, and 13.9%; 2-year OS rates were 94.6, 87.0, 67.5, and 24.2%, respectively. The C-index values of the novel index were 0.697 and 0.753 for PFS and OS prediction, which was superior to Ann Arbor stage and NCCN-IPI. CONCLUSION: The novel index including tumour burden and clinicopathological features may help predict outcome of DLBCL (clinicaltrials.gov identifier: NCT02928861).

Diagnostic performance of integrated whole-body 18F-FDG PET/MRI for detecting bone marrow involvement in indolent lymphoma: Comparison with 18F-FDG PET or MRI alone.

Purpose: To investigate the diagnostic performance of integrated whole-body 18F-FDG PET/MRI for detecting bone marrow involvement (BMI) in indolent lymphoma compared with 18F-FDG PET or MRI alone. Methods: Patients with treatment-naive indolent lymphoma who underwent integrated whole-body 18F-FDG PET/MRI and bone marrow biopsy (BMB) were prospectively enrolled. Agreement between PET, MRI, PET/MRI, BMB, and the reference standard was assessed using kappa statistics. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of each method were calculated. A receiver operating characteristic (ROC) curve was used to determine the area under the curve (AUC). AUCs of PET, MRI, PET/MRI, and BMB were compared using the DeLong test. Results: Fifty-five patients (24 males and 31 females; mean age: 51.1 ± 10.1 years) were included in this study. Of these 55 patients, 19 (34.5%) had BMI. Two patients were upstaged as extra bone marrow lesions were detected via PET/MRI. 97.1% (33/34) of participants were confirmed as BMB-negative in the PET-/MRI-group. PET/MRI (parallel test) and BMB showed excellent agreement with the reference standard (k = 0.843, 0.918), whereas PET and MRI showed moderate agreement (k = 0.554, 0.577). The sensitivity, specificity, accuracy, PPV, and NPV for identifying BMI in indolent lymphoma were 52.6%, 97.2%, 81.8%, 90.9%, and 79.5%, respectively, for PET; 63.2%, 91.7%, 81.8%, 80.0%, and 82.5%, respectively, for MRI; 89.5%, 100%, 96.4%, 100%, and 94.7%, respectively, for BMB; and 94.7%, 91.7%, 92.7%, 85.7%, and 97.1%, respectively, for PET/MRI (parallel test). According to ROC analysis, the AUCs of PET, MRI, BMB, and PET/MRI (parallel test) for detecting BMI in indolent lymphomas were 0.749, 0.774, 0.947, and 0.932, respectively. The DeLong test showed significant differences between the AUCs of PET/MRI (parallel test) and those of PET (P = 0.003) and MRI (P = 0.004). Regarding histologic subtypes, the diagnostic performance of PET/MRI for detecting BMI in small lymphocytic lymphoma was lower than that in follicular lymphoma, which was in turn lower than that in marginal zone lymphoma. Conclusion: Integrated whole-body 18F-FDG PET/MRI showed excellent sensitivity and accuracy for detecting BMI in indolent lymphoma compared with 18F-FDG PET or MRI alone, demonstrating that 18F-FDG PET/MRI is an optimal method and a reliable alternative to BMB. Trial registration: ClinicalTrials.gov (NCT05004961 and NCT05390632).

Fibroblast Activation Protein and Glycolysis in Lymphoma Diagnosis: Comparison of 68Ga-FAPI PET/CT and 18F-FDG PET/CT.

Our objective was to compare the diagnostic performance of 68Ga-labeled fibroblast activation protein (FAP) inhibitor (FAPI) and 18F-labeled FDG PET/CT in diagnosing lymphomas and to characterize the influence of FAP and glycolytic markers on tracer uptake by involved lesions. Methods: Participants with different lymphoma subtypes who were prospectively recruited from May 2020 to December 2021 underwent 68Ga-FAPI and 18F-FDG PET/CT. Immunohistochemistry was performed to evaluate FAP, hexokinase 2, and glucose transporter 1 (GLUT1) expression, and the paired-samples t test and Wilcoxon signed-rank test were used to compare parameters. The correlation between the immunochemistry results and tracer uptake was determined by the Spearman rank correlation coefficient. Results: In total, 186 participants (median age, 52 y [interquartile range, 41-64 y]; 95 women) were included. Dual-tracer imaging produced 3 types of imaging profiles. 18F-FDG PET possessed a higher staging accuracy (98.4%) than 68Ga-FAPI PET (86.0%). In 5,980 lymphoma lesions, 18F-FDG PET/CT detected more nodal (4,624 vs. 2,196) and extranodal (1,304 vs. 845) lesions than 68Ga-FAPI PET/CT. Additionally, 52 68Ga-FAPI-positive/18F-FDG-negative lesions and 2,939 68Ga-FAPI-negative/18F-FDG-positive lesions were observed. In many lymphoma subtypes, semiquantitative evaluation revealed no significant differences in SUVmax or target-to-liver ratios between 68Ga-FAPI and 18F-FDG PET/CT (P > 0.05). Interestingly, GLUT1 and hexokinase 2 were overexpressed both in lymphoma cells and in the tumor microenvironment, whereas FAP was expressed only in stromal cells. FAP and GLUT1 expression correlated positively with 68Ga-FAPI SUVmax (r = 0.622, P = 0.001) and 18F-FDG SUVmax (r = 0.835, P < 0.001), respectively. Conclusion: 68Ga-FAPI PET/CT was inferior to 18F-FDG PET/CT in diagnosing lymphomas with low FAP expression. However, the former may supplement the latter and help reveal the molecular profile of lymphomas.

Characterizing Concomitant Follicular Lymphoma and Gastric Carcinoma Using 68Ga-FAPI-04 and 18F-FDG PET/CT.

ABSTRACT: We herein report a case involving a 67-year-old man with concomitant progressive follicular lymphoma and gastric carcinoma. Baseline 18F-FDG PET/CT showed high metabolic activity in multiple nodal stations and a thickened gastric antrum wall, whereas 68Ga-FAPI-04 PET/CT depicted very intense tracer uptake in the gastric lesion but mild uptake in the nodes. After the treatment, complete remission from lymphadenopathy was achieved, whereas the gastric lesion accumulated more radiotracers compared with baseline levels. Despite our incorrect initial assumption of B-cell transformation, molecular imaging was able to profile the characteristics of these 2 diseases.

Risk Assessment in Diffuse Large B-Cell Lymphoma by Combining Baseline Metabolic Tumor Volume and Peking Criteria When Evaluating Series 18F-Fluorodeoxyglucose Positron Emission Tomography Scans.

This study aimed to determine the predictive and prognostic value of baseline metabolic tumor volume (MTV) and the Peking criteria from serial positron emission tomography (PET) scans in diffuse large B-cell lymphoma, including 300 newly diagnosed patients who were prospectively treated with 2-4 cycles of standard first-line treatment (clinicaltrials.gov identifier: NCT02928861). PET/computed tomography (CT) examinations were performed at baseline, after two (PET-2) or four cycles (PET-4). PET during the interim was evaluated using Deauville 5-point scales (5-PS), ΔSUVmax criteria, and the Peking criteria which interpreted based on the maximum standard uptake of the liver (SUVmax-liver). Peking criteria had better accuracy, positive predictive value (PPV), and specificity than other two methods. The MTV and Peking criteria both significantly predicted progression-free survival (PFS) and overall survival (OS). An MTV > 191 cm2 and Peking criteria of PET-2 and PET-4 > 1.6-fold SUVmax-liver was used as the cutoff for a positive result. PET-4 achieved higher accuracy, PPV, and specificity for 2-year PFS (83.3%, 86.7%, and 98.4%, respectively) and OS (92.6%, 73.3%, and 97.2%, respectively) than PET-2. Various prognostic models containing different risk factors were established via Cox regression analysis. The MTV and PET-2/PET-4 results were used to categorized patients into low-risk, intermediate-risk, and high-risk prognostic groups (with 0, 1, and 2 risk factors, respectively) (P < 0.0001). High burden MTV and positive PET-2 and PET-4 (>1.6-fold SUVmax-liver) could identify high-risk patients with 2-year PFS and OS of 0.0% and 26.3% (95% confidence interval [CI]: N/A to 54.3%). When PET-2 and PET-4 were evaluated by 5-PS, the 2-year PFS and OS from high risk patients of three-parameters model achieved 31.4% (95%CI: 6.9%-55.9%) and 42.7% (95%CI: 14.6%-70.7%). In conclusion, combining baseline MTV and any regular response on PET/CT evaluated using the Peking criteria can improve prognostic value. Serial PET/CT from baseline MTV to PET-4 may have relatively greater predictive power for poor prognosis in diffuse large B-cell lymphoma. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT02928861).

Detecting Fibroblast Activation Proteins in Lymphoma Using 68Ga-FAPI PET/CT.

Cancer-associated fibroblasts that overexpress fibroblast activation protein (FAP) are enriched in many epithelial carcinomas and in hematologic neoplasms. PET/CT with radiolabeled FAP inhibitor (FAPI) is a new diagnostic tool for visualizing the tumor stroma. This prospective study aimed to profile FAPs in different subtypes of lymphomas and explore the potential utility of 68Ga-FAPI PET/CT in lymphomas. Methods: In this prospective study, we recruited 73 lymphoma patients who underwent 68Ga-FAPI PET/CT and recorded and measured semiquantitative parameters and ratios of their scan results. FAPI expression was assessed by immunochemistry in samples obtained from 22 of the lymphoma patients. Results: We evaluated 11 patients with Hodgkin lymphoma and 62 with non-Hodgkin lymphoma (NHL). Significantly elevated FAP uptake was observed in Hodgkin lymphoma lesions, correlating with the intensity of FAP immunostaining (score, 3+). A positive association was found between the corresponding clinical classification of NHL and the 68Ga-FAPI uptake activity of the lesion. Aggressive NHL lesions, with moderate to strong FAP immunostaining (score, 2+ to 3+), exhibited intense to moderate 68Ga-FAPI uptake. Indolent NHL lesions showed weak FAP staining and mild to moderate 68Ga-FAPI uptake. No statistically significant correlation emerged between the sum of the product of the diameters and the corresponding SUVmax (P = 0.424). The tumor-to-liver ratios were 6.26 ± 4.17 in indolent NHL and more than 9 in other subtypes. Conclusion:68Ga-FAPI imaging can be used to detect FAP expression in lymphoma lesions and may be an alternate method for characterizing lymphoma profiles.

Diagnostic value of [68Ga]Ga-FAPI-04 in patients with colorectal cancer in comparison with [18F]F-FDG PET/CT.

Purpose: This study aimed to compare the diagnostic performance of [68Ga]Ga-FAPI-04 PET/CT and [18F]F-FDG PET/CT in primary and metastatic colorectal cancer (CRC) lesions. Methods: This single-center preliminary clinical study (NCT04750772) was conducted at the Peking University Cancer Hospital & Institute and included 61 participants with CRC who underwent sequential evaluation through PET/CT with [18F]F-FDG and [68Ga]Ga-FAPI-04. Their PET/CT images were analysed to quantify the uptake of the two tracers in the form of maximum standardised uptake (SUVmax) values and target-to-background ratio (TBR), which were then compared using Wilcoxon's signed-rank test. The final changes in the tumour-node-metastasis (TNM) stage of all participants were recorded. Results: Of all the participants, 21 were treatment naïve and 40 had been previously treated. In primary CRC lesions, the average TBRs of [68Ga]Ga-FAPI-04 and [18F]F-FDG were 13.3 ± 8.9 and 8.2 ± 6.5, respectively. The SUVmax of [68Ga]Ga-FAPI-04 in signet-ring/mucinous carcinomas (11.4 ± 4.9) was higher than that of [18F]F-FDG (7.9 ± 3.6) (P = 0.03). Both median SUVmax in peritoneal metastases and TBR in liver metastases of [68Ga]Ga-FAPI-04 were higher than those of [18F]F-FDG (5.2 vs. 3.8, P < 0.001; 3.7 vs. 1.9, P < 0.001, respectively). Compared with [18F]F-FDG PET/CT, clinical TNM staging based on [68Ga]Ga-FAPI-04 PET/CT led to upstaging and downstaging in 10 (16.4%) and 5 participants (8.2%), respectively. Therefore, the treatment options were changed in 13 participants (21.3%), including 9 with additional chemo/radiotherapy and/or surgery and others with avoidance or narrowed scope of surgery. Conclusion: [68Ga]Ga-FAPI-04 showed potential as a novel PET/CT tracer to detect lymph nodes and distant metastases, which improved CRC staging, thus prompting the optimisation or adjustment of treatment decisions.

Morphological changes of blocklets during the gelatinization process of tapioca starch.

After combined hydrolysis by α-amylase and ß-amylase at room temperature, spherical blocklets in diameters of 27-60nm were observed on the surface of tapioca starch granules by scanning electron micrography (SEM). Tapioca starch (1%, w/w, db, distilled water) was heated by using a rapid visco analyzer (RVA) in four different programs, then the samples were settled and freeze dried, respectively. The SEM images showed that the blocklets swelled at 52°C; the swollen blocklets deformed to olive shape, and linked by molecular chains, formed bead-like structure at 62°C; they started to merge at 72°C (pasting temperature); then the blocklets fused together and their shapes disappeared completely, and the gel network formed at 95°C. Furthermore, the morphological changes of the blocklets were not simultaneously.

The correlation of neutrophil-to-lymphocyte ratio with the presence and activity of myasthenia gravis.

Though the pathogenesis of myasthenia gravis (MG) is not fully understood, the role of inflammation has been well appreciated in the development of MG. We aimed to investigate the role of neutrophil-to-lymphocyte ratio (NLR) in MG patients and the relationship between the NLR and the activity of the disease. A total number of 172 MG patients and 207 healthy controls (HC) were enrolled in this study. The MG patients were divided into tertiles according to NLR (low NLR < 1.58, n = 57; intermediate NLR 1.58-2.33, n = 57 and high NLR > 2.33, n = 58). The disease activity assessment was performed according to the standard criteria established by the Myasthenia Gravis Foundation of America. Patients with MG had significantly higher NLR when compared with the HC group (P < 0.0001). The NLR levels were higher in the MG patients with severe disease activity than those with mild disease activity (P < 0.001), meanwhile, median NLR was statistically higher in MG patients with myasthenic crisis (MC) than those without MC (P < 0.001). Incidences of severe disease activity and MC were both higher in the high NLR group, compared to low and intermediate NLR groups (both P < 0.001). Multivariate logistic regression analysis suggested that elevated NLR was an independent predictor of severe disease activity (odds ratio = 13.201, CI% = 1.418-122.938, P = 0.023). These results indicate that NLR may be a simple and useful potential marker in indicating disease activity in patients with MG.

Low serum albumin concentrations are associated with disease severity in patients with myasthenia gravis.

Serum albumin (S-Alb) is a widely used biomarker of nutritional status and disease severity in patients with autoimmune diseases. We investigated the correlation between S-Alb and the severity of myasthenia gravis (MG).A total number of 166 subjects were recruited in the study. Subjects were divided into 3 groups (T1 to T3) by S-Alb levels: T1: 21.1 to 38.4 g/L, T2: 38.5 to 41.5 g/L, T3: 41.6 to 48.9 g/L. Regression analysis was performed to determine the correlation of initial albumin concentrations and the severity of disease of MG.Lower levels of S-Alb were observed in subjects with increased disease severity than those with slight disease severity, meanwhile, incidence of myasthenia crisis increased in the lower albumin tertiles (P < 0.001). The disease severity assessment was performed according to the criteria established by the Myasthenia Gravis Foundation of America. After adjusting for age, sex, body mass index (BMI), and duration of disease, it showed that higher S-Alb concentrations were associated with lower disease severity. Odds ratios (ORs) of T2 to T3 were 0.241 (95% CI: 0.103-0.566, P < 0.001), 0.140 (95% CI: 0.054-0.367, P < 0.001) when compared with subjects in the T1, respectively. When subjects were stratified into hypoalbuminemia and normal albumin groups, we found that the association between S-Alb and MG remained significant in the hypoalbuminemia group only (OR: 0.693, 95% CI: 0.550-0.874, P = 0.002) after further adjustment for age, sex, BMI, and duration of disease.This is the first study to demonstrate that S-Alb was independently associated with MG severity. In patients with low S-Alb, S-Alb concentration could be a potential biomarker for MG disability.