Total-body PET/CT with half-dose [68 Ga]Ga-PSMA-11 for biochemical recurrent prostate cancer: comparable diagnostic value to short axial field-of-view PET/CT with full-dose [68 Ga]Ga-PSMA-11.

PURPOSE: The objective of this study was to evaluate the diagnostic performance and image quality of total-body positron emission tomography/computed tomography (PET/CT) imaging using a half-dose of [68 Ga]Ga-prostate specific membrane antigen ([68 Ga]Ga-PSMA) radiotracer, compared to conventional short axial field-of-view PET/CT imaging using a full dose of [68 Ga]Ga-PSMA. METHODS: This retrospective study enrolled 52 patients with biochemical recurrent (BCR) prostate cancer after radical prostatectomy who underwent total-body PET/CT with a half-dose (0.9-1.1 MBq/kg) of [68 Ga]Ga-PSMA. These patients were matched by baseline characteristics to another 52 BCR patients after prostatectomy who underwent conventional PET/CT with a full dose (1.8-2.2 MBq/kg) of [68 Ga]Ga-PSMA. The half-dose group was further divided into 5-min (G5) and 2-min (G2) acquisition subgroups. Image quality was assessed through subjective analysis using a 5-point scale and objective measurements of standard uptake value maximum (SUVmax), standard uptake value mean (SUVmean), background variation (BV) of the liver, blood pool, and parotid glands. Additionally, SUVmax and tumor-to-background ratio (TBR) were calculated for lesions. RESULTS: No significant difference in subjective image quality was found between the G2 and full-dose groups (p > 0.05). PET/CT image quality was significantly higher for the G5 versus G2 (p < 0.001) and full-dose groups (p < 0.001). TBR did not differ between the G2 and full-dose groups (4.23 ± 5.21 vs 4.22 ± 3.97, p = 0.99). Liver BV was significantly lower for G2 versus full-dose groups (0.16 ± 0.03 vs 0.20 ± 0.05, p < 0.001). CONCLUSIONS: Total-body PET/CT with a half-dose [68 Ga]Ga-PSMA yields image quality superior or comparable to that of conventional PET/CT. The utilization of total-body [68 Ga]Ga-PSMA PET/CT meets the diagnostic demands of BCR patients, particularly those who exhibit reduced tolerance to prolonged horizontal positioning and scan durations, while simultaneously reducing radiation exposure for the subjects.

2-[18F]FDG PET-based quantification of lymph node metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer.

BACKGROUND AND PURPOSE: The pre-surgical estimation of lymph node (LN) metastasis in colorectal cancer (CRC) poses a significant diagnostic predicament. The associations between LN morphology, density, and metabolic heterogeneity and LN metastasis status in CRCs have been seldomly examined through the lens of radiomics. This research aimed to assess 2-[18F]FDG PET-based quantification of intratumoral metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer. MATERIALS AND METHODS: The construction of the model utilized data from 264 CRC patients, all of whom underwent preoperative 2-[18F]FDG PET/CT. Radiomic features were extracted from PET and CT images of LNs. Least absolute shrinkage and selection operator (LASSO) regression was implemented for selecting pertinent imaging features with a tenfold cross-validation. The predictive accuracy for LN metastasis status was juxtaposed against traditional methodologies (comprising CT-reported LN status and PET/CT-reported LN status) by deploying the receiver operating characteristic (ROC) curve analysis. The radiomics signature was evaluated based on discrimination, calibration, and clinical utility parameters. The model was further subjected to validation using an independent cohort of 132 patients from the period of January 2012 to June 2020. RESULTS: The radiomics model was composed of eight significant radiomic features (five from PET and three from CT), encapsulating metabolic and density heterogeneity. The radiomics signature (area under the curve (AUC), 0.908) showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.563, P < 0.001) and PET/CT-reported LN status (AUC, 0.64, P < 0.001) for predicting LN-positive or LN-negative status. The radiomics signature (AUC, 0.885) also showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.587, P < 0.001) and PET/CT-reported LN status (AUC, 0.621, P < 0.001) to identify N1 and N2. This signature maintained its independence from clinical risk factors and exhibited robustness in the validation test set. Decision curve analysis attested to the clinical utility of the radiomics signature. CONCLUSIONS: The radiomics signature based on 2-[18F]FDG PET/CT, which derived image features directly from LNs irrespective of clinical risk factors, displayed enhanced diagnostic performance compared to conventional CT or PET/CT-reported LN status. This allows for the identification of pre-surgical LN metastasis status and facilitates a patient-specific prediction of LN metastasis status in CRC patients.

Assessing dynamic metabolic heterogeneity in prostate cancer patients via total-body [68Ga]Ga-PSMA-11 PET/CT imaging: quantitative analysis of [68Ga]Ga-PSMA-11 uptake in pathological lesions and normal organs.

PURPOSE: This study aimed to quantitatively assess [68Ga]Ga-PSMA-11 uptake in pathological lesions and normal organs in prostate cancer using the total-body [68Ga]Ga-PSMA-11 PET/CT and to characterize the dynamic metabolic heterogeneity of prostate cancer. METHODS: Dynamic total-body [68Ga]Ga-PSMA-11 PET/CT scans were performed on ten prostate cancer patients. Manual delineation of volume-of-interests (VOIs) was performed on multiple normal organs displaying high [68Ga]Ga-PSMA-11 uptake, as well as pathological lesions. Time-to-activity curves (TACs) were generated, and the four compartment models including one-tissue compartmental model (1T1k), reversible one-tissue compartmental model (1T2k), irreversible two-tissue compartment model (2T3k) and reversible two-tissue compartmental model (2T4k) were fitted to each tissue TAC. Various rate constants, including K1 (forward transport rate from plasma to the reversible compartment), k2 (reverse transport rate from the reversible compartment to plasma), k3 (tracer binding on the PSMA-receptor and its internalization), k4 (the externalization rate of the tracer) and Ki (net influx rate), were obtained. The selection of the optimal model for describing the uptake of both lesions and normal organs was determined using the Akaike information criteria (AIC). Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values for differentiating physiological and pathological [68Ga]Ga-PSMA-11 uptake. RESULTS: Both 1T1k and 1T2k models showed relatively high AIC values compared to the 2T3k and 2T4k models in both pathological lesions and normal organs. The kinetic behavior of pathological lesions was better described by the 2T3k model compared to the 2T4k model, while the normal organs were better described by the 2T4k model. Significant variations in kinetic metrics, such as K1, k2, and k3, and Ki, were observed among normal organs with high [68Ga]Ga-PSMA-11 uptake and pathological lesions. The high Ki value in normal organs was primarily determined by elevated K1 and low k3, rather than k2. Conversely, the high Ki value in pathological lesions, ranking second to the kidney and similar to salivary glands and spleen, was predominantly determined by the highest k3 value. Notably, k3 exhibited the highest performance in distinguishing between physiological and pathological [68Ga]Ga-PSMA-11 uptake, with an area under the curve (AUC) of 0.844 (95% CI, 0.773-0.915), sensitivity of 82.9%, and specificity of 74.1%. The k3 values showed better performance than SUVmean (AUC, 0.659), SUVmax (AUC, 0.637), and other kinetic parameter including K1 (AUC, 0.604), k2 (AUC, 0.634), and Ki (AUC, 0.651). CONCLUSIONS: Significant discrepancies in kinetic metrics were detected between pathological lesions and normal organs, despite their shared high uptake of [68Ga]Ga-PSMA-11. Notably, the k3 value exhibits a noteworthy capability to distinguish between pathological lesions and normal organs with elevated [68Ga]Ga-PSMA-11 uptake. This discovery implies that k3 holds promise as a prospective imaging biomarker for distinguishing between pathologic and non-specific [68Ga]Ga-PSMA-11 uptake in patients with prostate cancer.

The superior detection rate of total-body [68Ga]Ga-PSMA-11 PET/CT compared to short axial field-of-view [68Ga]Ga-PSMA-11 PET/CT for early recurrent prostate cancer patients with PSA < 0.2 ng/mL after radical prostatectomy.

BACKGROUND AND PURPOSE: [68Ga]Ga-PSMA PET imaging has been extensively utilized for the detection of biochemical recurrence (BCR) in prostate cancer. However, the detection rate declines to merely 10-40% when PSA levels are < 0.2 ng/mL employing short axial field-of-view (SAFOV) PET. Prior studies exhibited superior detection rates with total-body [68Ga]Ga-PSMA-11 PET compared to SAFOV [68Ga]Ga-PSMA-11 PET in BCR patients with PSA > 0.2 ng/mL. Nevertheless, the diagnostic utility of total-body [68Ga]Ga-PSMA-11 PET for BCR patients when PSA is < 0.2 ng/mL remains unclear. This study aimed to assess whether total-body [68Ga]Ga-PSMA-11 PET/CT could improve the detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT in BCR patients with PSA < 0.2 ng/mL. METHODS: Eighty BCR patients with PSA < 0.2 ng/mL underwent total-body [68Ga]Ga-PSMA-11 PET/CT. These patients were matched by baseline qualities to another 80 patients who received SAFOV [68Ga]Ga-PSMA-11 PET/CT. The detection rates of total-body [68Ga]Ga-PSMA-11 PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT were compared utilizing a chi-square test and stratified analysis. Image quality of total-body [68Ga]Ga-PSMA PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT was assessed based on subjective scoring and objective parameters. The objective parameters measured were SUVmax, SUVmean, standard deviation (SD) of SUV, and signal-to-noise ratio (SNR) of liver and gluteus maximus. RESULTS: The image quality of total-body [68Ga]Ga-PSMA PET/CT was superior to that of SAFOV [68Ga]Ga-PSMA-11 PET/CT in both early and delayed scans. The detection rate of total-body [68Ga]Ga-PSMA PET/CT for BCR patients with PSA < 0.2 ng/mL was significantly higher than that of SAFOV [68Ga]Ga-PSMA-11 PET/CT (73.75% vs. 43.75%, P < 0.001). Total-body [68Ga]Ga-PSMA PET/CT resulted in noteworthy modifications to the treatment regimen when contrasted with SAFOV [68Ga]Ga-PSMA-11 PET/CT. CONCLUSIONS: In BCR patients with PSA < 0.2 ng/mL, total-body [68Ga]Ga-PSMA-11 PET/CT not only demonstrated a significantly higher detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT but also led to significant alterations in treatment regimens.

Intelligent ultrafast total-body PET for sedation-free pediatric [18F]FDG imaging.

PURPOSE: This study aims to develop deep learning techniques on total-body PET to bolster the feasibility of sedation-free pediatric PET imaging. METHODS: A deformable 3D U-Net was developed based on 245 adult subjects with standard total-body PET imaging for the quality enhancement of simulated rapid imaging. The developed method was first tested on 16 children receiving total-body [18F]FDG PET scans with standard 300-s acquisition time with sedation. Sixteen rapid scans (acquisition time about 3 s, 6 s, 15 s, 30 s, and 75 s) were retrospectively simulated by selecting the reconstruction time window. In the end, the developed methodology was prospectively tested on five children without sedation to prove the routine feasibility. RESULTS: The approach significantly improved the subjective image quality and lesion conspicuity in abdominal and pelvic regions of the generated 6-s data. In the first test set, the proposed method enhanced the objective image quality metrics of 6-s data, such as PSNR (from 29.13 to 37.09, p < 0.01) and SSIM (from 0.906 to 0.921, p < 0.01). Furthermore, the errors of mean standardized uptake values (SUVmean) for lesions between 300-s data and 6-s data were reduced from 12.9 to 4.1% (p < 0.01), and the errors of max SUV (SUVmax) were reduced from 17.4 to 6.2% (p < 0.01). In the prospective test, radiologists reached a high degree of consistency on the clinical feasibility of the enhanced PET images. CONCLUSION: The proposed method can effectively enhance the image quality of total-body PET scanning with ultrafast acquisition time, leading to meeting clinical diagnostic requirements of lesion detectability and quantification in abdominal and pelvic regions. It has much potential to solve the dilemma of the use of sedation and long acquisition time that influence the health of pediatric patients.

Comparison of parametric imaging and SUV imaging with [68 Ga]Ga-PSMA-11 using dynamic total-body PET/CT in prostate cancer.

PURPOSE: Standardized uptake value (SUV) has been prevalently used to measure [68 Ga]Ga-PSMA-11 activity in prostate cancer, but it is susceptible to multiple factors. Parametric imaging allows for absolute quantification of tracer uptake and provides a better diagnostic accuracy that is crucial for lesion detection. However, the clinical significance of total-body parametric imaging of [68 Ga]Ga-PSMA-11 remains to be fully assessed. Therefore, the aim of our study is to delve into the diagnostic implications of total-body parametric imaging of [68 Ga]Ga-PSMA-11 PET/CT for patients with prostate cancer. METHODS: Twenty prostate cancer patients were included and underwent a dynamic total-body [68 Ga]Ga-PSMA-11 PET/CT scan. An irreversible two-tissue compartment model (2T3k) was fitted for each tissue time-to-activity curve, and the net influx rate (Ki) was obtained. The image quality and semi-quantitative analysis of lesion-to-background ratio (LBR), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were compared between parametric images and SUV images. RESULTS: Kinetic modeling using 2T3k demonstrated favorable model fitting in both normal organs and lesions. All of the lesions detected on SUV images (55-60 min) could be detected on Ki images. The correlation between Ki, SUVmean, and SUVmax in both normal organs and pathological lesions was found to be positive and statistically significant. Conversely, a moderate positive correlations were found between Ki and K1 (R = 0.69, P < 0.001; R = 0.61, P < 0.001) and Ki and k3 (R = 0.69, P < 0.001; R = 0.62, P < 0.001), in normal organs and pathological lesions, respectively. Visual assessment in Ki images showed less image noise and higher lesions conspicuity compared to SUV images. Ki image-derived LBR, SNR, and CBR of pathological lesions including primary tumors (PTs), lymph node metastases (LNMs) and bone metastases (BMs), exhibited remarkably higher folds (1.4-3.6 folds) compared to those derived from SUV of corresponding lesions. CONCLUSIONS: Total-body parametric imaging of [68 Ga]Ga-PSMA-11 enhanced lesion contrast and improved lesion detectability compared to SUV images. This may potentially serve as an imaging biomarker and theranostic tool for precise diagnosis and treatment evaluation in prostate cancer patients.

Sedation-free pediatric [18F]FDG imaging on totalbody PET/CT with the assistance of artificial intelligence.

PURPOSE: While sedation is routinely used in pediatric PET examinations to preserve diagnostic quality, it may result in side effects and may affect the radiotracer's biodistribution. This study aims to investigate the feasibility of sedation-free pediatric PET imaging using ultra-fast total-body (TB) PET scanners and deep learning (DL)-based attenuation and scatter correction (ASC). METHODS: This retrospective study included TB PET (uExplorer) imaging of 35 sedated pediatric patients under four years old to determine the minimum effective scanning time. A DL-based ASC method was applied to enhance PET quantification. Both quantitative and qualitative assessments were conducted to evaluate the image quality of ultra-fast DL-ASC PET. Five non-sedated pediatric patients were subsequently used to validate the proposed approach. RESULTS: Comparisons between standard 300-second and ultra-fast 15-second imaging, CT-ASC and DL-ASC ultra-fast 15-second images, as well as DL-ASC ultra-fast 15-second images in non-sedated and sedated patients, showed no significant differences in qualitative scoring, lesion detectability, and quantitative Standard Uptake Value (SUV) (P = ns). CONCLUSIONS: This study demonstrates that pediatric PET imaging can be effectively performed without sedation by combining ultra-fast imaging techniques with a DL-based ASC. This advancement in sedation-free ultra-fast PET imaging holds potential for broader clinical adoption.

Baseline PSMA-PET/CT as a predictor of PSA persistence following radical prostatectomy in high-risk nonmetastatic prostate cancer patients receiving neoadjuvant therapy.

BACKGROUND: The precise staging and proper management of high-risk prostate cancer (PCa) continues to be a challenge. We aimed to demonstrate the prognostic value of baseline prostate-specific membrane antigen-ligand positron emission tomography/computed tomography (PSMA-PET/CT) in high-risk, nonmetastatic PCa patients who received neoadjuvant hormonal or chemohormonal treatment followed by radical prostatectomy (RP). METHODS: We performed retrospective analyses of 70 patients with high-risk, nonmetastatic PCa confirmed by biopsy between 2018 and 2021. All patients underwent neoadjuvant therapy followed by RP and pelvic lymph node dissection (PLND); PSMA-PET/CT was performed before initiation of neoadjuvant therapy. Acquired image information and clinical characteristics/outcomes were examined for possible associations. RESULTS: Among 70 high-risk PCa patients, median age was 69 years old and median prostate specific antigen (PSA) at presentation was 58.5 ng/mL. Thirty (42.9%) patients had uptake of the PSMA tracer only in the primary PCa lesions and 40 (57.1%) patients had PSMA-positive lesions in regional or distant sites. Sixteen (32%) localized PCa patients defined by pre-PET magnetic resonance imaging were found to have locally advanced PCa based on PSMA-PET/CT. Fifteen (30%) localized PCa patients and 7 (35%) locally advanced PCa patients were upstaged to metastatic PCa. The sensitivity and specificity of PSMA-PET/CT for the detection of lymph node involvement were 90.9% and 69.5%, respectively, with a positive prediction value of 35.7% and negative prediction value of 97.6%. The diagnostic accuracy was 72.9%. Univariate analysis showed upstaging, tumor stage, and metastasis location based on PSMA-PET/CT are predictors to PSA persistence after surgery, while multivariate logistic regression analysis showed only the tumor stage based on PSMA-PET/CT remained an independent predictor of the outcome. CONCLUSIONS: This study further highlights the accuracy and necessity of PSMA-PET/CT in newly diagnosed, high-risk, nonmetastatic PCa patients.

Relationship between the expression of PD-L1 and 18F-FDG uptake in pancreatic ductal adenocarcinoma.

BACKGROUND: PD-L1 promotes glycolysis in tumour cells. We observed a correlation between high PD-L1 expression and high 18F-FDG uptake in patients with pancreatic ductal adenocarcinoma (PDAC) in a previous study. This study aims to determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in PDAC and to elucidate its rationality by integrated analyses. METHODS: For bioinformatics analysis, WGCNA, GSEA and TIMER were applied to analyse the pathways and hub genes associated with PD-L1 and glucose uptake. 18F-FDG uptake assay was used to determine the glucose uptake rate of PDAC cells in vitro. Related genes expression were verified by RT-PCR and western blot. A retrospective analysis was performed on 47 patients with PDAC who had undergone 18F-FDG PET/CT. Maximum standardised uptake values (SUVmax) were determined. The usefulness of SUVmax for evaluating PD-L1 status was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: Bioinformatics analysis showed that several signalling pathways are associated with both PD-L1 expression and tumour glucose uptake, among which JAK-STAT may be an important one. By in vitro experiments, the regulatory role of PD-L1 on glucose uptake was demonstrated, and its dependency on the JAK-STAT pathway was also verified by the rescue study. The SUVmax of PD-L1-positive patients was significantly higher than PD-L1-negative in tumour cells (TCs) (6.1 ± 2.3 vs. 11.1 ± 4.2; P < 0.001), and in tumour-infiltrating immune cells (TIICs) (6.4 ± 3.2 vs. 8.4 ± 3.5; P < 0.001). In a multivariate analysis, SUVmax was significantly associated with PD-L1 expression in TCs and TIICs (P < 0.001 and P = 0.018, respectively). Using SUVmax cut-off values of 8.15 and 7.75, PD-L1 status in TCs and TIICs could be predicted with accuracies of 91.5% and 74.5%, respectively. CONCLUSION: Higher 18F-FDG uptake by PDAC is associated with elevated PD-L1 expression. JAK-STAT is an important pathway that mediates PD-L1 to promote glucose uptake in PDAC.

Relationship between SUVmax on 18F-FDG PET and PD-L1 expression in hepatocellular carcinoma.

PURPOSE: Our study was to investigate the correlation between 18F-FDG uptake in HCC and tumor PD-L1 expression in HCC, and assess the value of 18F-FDG PET/CT imaging for predicting PD-L1 expression in HCC. METHODS: A total of 102 patients with confirmed HCC were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of HCC lesions were assessed using 18F-FDG PET/CT. The correlation between PD-L1 expression and the clinicopathological were evaluated by the Cox proportional hazards model and the Kaplan-Meier survival analysis. RESULTS: The SUVmax of HCC primary tumors was higher in patients with poorly differentiated HCC, large tumor size, portal vein tumor thrombus, lymph node and distant metastases, and death. The SUVmax of HCC are correlated with the PD-L1 expression and the number of cytotoxic T cells and M2 macrophage infiltration. PD-L1 expression was significantly correlated with tumor SUVmax, tumor differentiation, tumor size, portal vein tumor thrombosis, and patient survival status and infiltrating M2 macrophages. Further, our results confirmed that SUVmax, portal vein tumor thrombosis, and the number of infiltrating M2 macrophages were closely related to PD-L1 expression and were independent risk factors by multivariate analysis. The combined assessment of SUVmax values and the presence of portal vein tumor thrombosis by 18F-FDG PET/CT imaging can help determine PD-L1 expression in HCC. CONCLUSIONS: FDG uptake in HCC was positively correlated with the PD-L1 expression and the number of cytotoxic T cells and M2 macrophage infiltration. The combined use of SUVmax and portal vein tumor thrombosis by PET/CT imaging assess the PD-L1 expression better in HCC. These findings also provide a basis for clinical studies to assess the immune status of tumors by PET/CT.

The feasibility of ultra-early and fast total­body [68 Ga]Ga-FAPI-04 PET/CT scan.

PURPOSE: [68 Ga]Ga-FAPI-04 PET/CT has been widely used in oncology patients. The patients need to lie still for 20-30 min during scan after waiting for 60 min post-tracer injection in traditional [68 Ga]Ga-FAPI-04 PET/CT scan. This is difficult for some patients who are intolerant to prolonged horizontal positioning and waiting time. Therefore, we evaluated the diagnostic value of the images obtained in ultra-early and fast scan (5-min p.i., 30-s acquisition time) by the total-body [68 Ga]Ga-FAPI-04 PET/CT and to investigate whether they could meet the requirements of clinical diagnosis. METHODS: Total-body [68 Ga]Ga-FAPI-04 PET/CT was conducted in 12 patients at the Renji Hospital. Patients underwent PET with two acquisitions: 5-min p.i. and 30-s acquisition time (ultra-early and fast imaging) and 60-min p.i. and 300-s acquisition time (traditional imaging). Mean [68 Ga]Ga-FAPI-04 injection dose was 1.85 MBq/kg. RESULTS: Forty-four lesions were detected in 12 patients on traditional imaging. All the 44 lesions on conventional imaging could also detected by ultra-early and fast imaging. For all the 12 patients, the tumor stage did not change, as same lesions were visible for every case in both images. There was no statistically significant difference in SUVmax of lesions between ultra-early and fast imaging and traditional imaging (12.5 ± 8.7 vs 13.7 ± 8.5, P = 0.528). Background bloodpool (4.0 ± 0.6 vs 0.9 ± 0.2, P < 0.001)and liver (2.5 ± 0.7 vs 1.0 ± 0.5, P < 0.001)at traditional imaging showed a significant decrease in SUVmean compared to ultra-early and fast imaging. CONCLUSIONS: Ultra-early and fast imaging versus traditional [68 Ga]Ga-FAPI-04 imaging resulted in equivalent tumor detection and lesion uptake. Ultra-early and fast total-body [68 Ga]Ga-FAPI-04 PET/CT scan could meet clinical diagnostic requirements for patients with poor tolerant to prolonged horizontal positioning and waiting time.

Tumor-to-blood ratio for assessment of fibroblast activation protein receptor density in pancreatic cancer using [68Ga]Ga-FAPI-04.

PURPOSE: [68Ga]Ga-FAPI PET/CT has been widely used in clinical diagnosis and radiopharmaceutical therapy. In this study, tumor-to-blood ratio (TBR) was evaluated as a powerful tool for semiquantitative assessment of [68Ga]Ga-FAPI-04 tumor uptake and as an effective index for tumors with high FAP expression in theranostics. METHODS: Nine patients with pancreatic cancer underwent a 60-min dynamic PET/CT scan by total-body PET/CT (with a long AFOV of 194 cm) after injection of [68Ga]Ga-FAPI-04. After dynamic PET/CT scan, three patients received chemotherapy and underwent the second dynamic scan to evaluate treatment response. Time-activity curves (TACs) were obtained by drawing regions of interest for primary pancreatic lesions and metastatic lesions. The lesion TACs were fitted using four compartment models by the software PMOD PKIN kinetic modeling. The preferred pharmacokinetic model for [68Ga]Ga-FAPI-04 was evaluated based on the Akaike information criterion. The correlations between simplified methods for quantification of [68Ga]Ga-FAPI-04 (SUVs; tumor-to-blood ratios [TBRs]) and the total distribution volume (Vt) estimates obtained from pharmacokinetic analysis were calculated. RESULTS: In total, 9 primary lesions and 25 metastatic lesions were evaluated. The reversible two-tissue compartment model (2TCM) was the most appropriate model among the four compartment models. The total distribution volume Vt values derived from 2TCM varied significantly in pathological lesions and background regions. A strong positive correlation was observed between TBRmean and Vt from the 2TCM model in pathological lesions (R2=0.92, P<0.001). The relative difference range for TBRmean was 2.1% compared to the reduction rate of Vt in the patients who were treated with chemotherapy. CONCLUSIONS: A strong positive correlation was observed between TBRmean and Vt for [68Ga]Ga-FAPI-04. TBRmean reflects FAP receptor density better than SUVmean and SUVmax, and would be the preferred measurement tool for semiquantitative assessment of [68Ga]Ga-FAPI-04 tumor uptake and as a means for evaluating treatment response.

Total-body [68 Ga]Ga-PSMA-11 PET/CT improves detection rate compared with conventional [68 Ga]Ga-PSMA-11 PET/CT in patients with biochemical recurrent prostate cancer.

PURPOSE: The purpose of this study was to assess whether total-body [68 Ga]Ga-PSMA-11 PET/CT could improve the detection rate compared with conventional [68 Ga]Ga-PSMA-11 PET/CT in patients with biochemical recurrent prostate cancer. METHODS: Two hundred biochemical recurrent prostate cancer patients with similar clinicopathological characteristics were included, of whom 100 patients underwent early total-body [68 Ga]Ga-PSMA-11 PET/CT and diuretic-delayed total-body [68 Ga]Ga-PSMA-11 PET/CT, and the other 100 patients received early conventional [68 Ga]Ga-PSMA-11 PET/CT and diuretic-delayed conventional [68 Ga]Ga-PSMA-11 PET/CT. The detection rates of total-body [68 Ga]Ga-PSMA-11 PET/CT and conventional [68 Ga]Ga-PSMA-11 PET/CT were compared using a chi-square test and stratified analysis. The image quality of total-body [68 Ga]Ga-PSMA PET/CT and conventional [68 Ga]Ga-PSMA-11 PET/CT was compared based on subjective scoring and objective parameters. Subjective scoring was conducted from background noise and lesion prominence using a 5-point scale. Objective parameters were evaluated by SUVmax, SUVmean, the standard deviation (SD) of SUV, and the signal-to-noise ratio (SNR) of liver and gluteus maximus. The SUVmax of the recurrent lesions was also measured. RESULTS: The liver SD of the total-body [68 Ga]Ga-PSMA-11 PET/CT was significantly lower than that of conventional [68 Ga]Ga-PSMA-11 PET/CT, the SNR was significantly higher than that of conventional [68 Ga]Ga-PSMA-11 PET/CT, and the subjective evaluation was significantly better than that of conventional [68 Ga]Ga-PSMA-11 PET/CT. The detection rate of total-body [68 Ga]Ga-PSMA PET/CT for biochemical recurrence of prostate cancer was significantly higher than that of conventional [68 Ga]Ga-PSMA-11 PET/CT (91.0% vs. 74.0%, P = 0.003). Total-body [68 Ga]Ga-PSMA-11 PET/CT had better detection efficiency for patients with a Gleason score ≤ 8 or PSA ≤ 2 ng/ml. The advantages of diuretic-delayed total-body [68 Ga]Ga-PSMA-11 PET/CT were more obvious. CONCLUSION: Total-body [68 Ga]Ga-PSMA-11 PET/CT could significantly improve the detection rate compared with conventional [68 Ga]Ga-PSMA-11 PET/CT in patients with biochemical recurrent prostate cancer.

Feasibility of acquisitions using total-body PET/CT with a half-dose [68Ga]Ga-FAPI-04 activity in oncology patients.

BACKGROUND: [68Ga]Ga-FAPI-04 (gallium-68-labeled fibroblast activation protein inhibitor-04) PET/CT has been widely used in diagnosing malignant tumors. Total-body PET/CT has a long axial field of view and provides higher sensitivity compared to traditional PET/CT. However, whether the reduced injected dose of [68Ga]Ga-FAPI-04 could obtain qualified imaging has not been evaluated. PURPOSE: To explore the effect of half-dose [68Ga]Ga-FAPI-04 on image quality and tumor detectability in oncology patients. METHODS: A total of twenty-seven patients with tumors or clinically suspected tumors were included, and all patients were scanned with total-body PET/CT after an injected dose of 0.84-1.14 MBq/kg [68Ga]Ga-FAPI-04. All patients obtained superior image quality with 300 s original acquisition time. Images were reconstructed using 180 s, 120 s, 60 s, 40 s, 30 s, 20 s scanning duration by ordered subset expectation maximization algorithm. The subjective image quality of all patients in each time group was scored using 5-point Likert scale. Mediastinal blood pool, liver, spleen, and muscle were analyzed as background using semi-quantitative parameters maximum standardized uptake values (SUVmax), mean standardized uptake values (SUVmean), standard deviation (SD), and signal to noise ratio (SNR). The lesion detection rate, SUVmax, and tumor-to-background ratio (TBR) were calculated for tumors confirmed by pathology. RESULTS: The subjective image quality score decreased with the shortening of scanning time; however, both 180 s and 120 s images met the diagnostic requirements in terms of overall quality, lesion conspicuity, and image noise. The SUVmax of background increased with the reduction of scanning time, while the SUVmean was relatively stable. With the shortening of scanning time, the SD gradually increased, and the SNR gradually decreased, which was consistent with subjective image quality scores. In 180 s and 120 s images, all 11 primary lesions and 79 metastatic lesions were detected. The SUVmax of tumor focus showed an increasing trend as same as the background. Compared with 300 s, the TBR muscle had no statistical difference in 180 s and 120 s. CONCLUSIONS: Half-dose [68Ga]Ga-FAPI-04 in total-body PET/CT imaging can shorten the acquisition time to 120 s with acceptable subjective image quality and 100% tumor detection rate. Total-body PET/CT imaging with a half-dose [68Ga]Ga-FAPI-04 and reduced acquisition time can be used in radiation-sensitive and poor tolerant to prolong horizontal positioning and waiting time populations such as children and gravidas.

Determination of optimal 68 Ga-PSMA PET/CT imaging time in prostate cancers by total-body dynamic PET/CT.

BACKGROUND: 68 Ga-PSMA PET/CT has been widely used in patients with prostate cancer. Due to the limited axial field of view of conventional PET scanners, whole-body dynamic 68 Ga-PSMA PET/CT has not been performed. We investigated the time-activity curves (TACs) of prostate cancer pathological lesions and physiologic bladder activity to determine the optimal 68 Ga-PSMA PET/CT imaging time by total-body (TB) PET/CT. METHODS: Dynamic TB-PET performed on 11 patients with prostate cancer was analyzed. TACs were obtained by drawing regions of interest in normal organs and pathological lesions (primary prostate lesions and lymph nodes and bone metastases). We evaluated the 68 Ga-PSMA uptake pattern of normal organs, urinary bladder, and pathological lesions. RESULTS: The urinary bladder TAC increased slowly between 180 and 330 s post-injection and then rapidly between 5.5 and 60.0 min post-injection. The pathological lesion uptake increased rapidly during the first 5 min post-injection and then slowly through the remaining 55 min. Six minutes post-injection was the optimal time with the highest pathological lesion SUVmean values still higher than the urinary bladder activity value. However, these prostate lesion, lymph node metastasis, and bone metastasis SUVmean values were one-third, one-half, and one-half the corresponding values 60 min post-injection, suggesting that early imaging might miss low PSMA uptake lesions. A minimum of 35 min post-injection was required for the pathological lesions to have SUVmean values similar to the corresponding values at 60 min post-injection (all P > 0.05), even though the pathological lesion SUVmean values showed a continuous upward trend through the 60 min. CONCLUSIONS: Combining early dynamic 68 Ga-PSMA PET (75-360 s) and conventional static imaging 60 min post-injection could avoid the urinary bladder activity interference to better detect pathological lesions and lesions with relatively low PSMA uptake. The pathological lesion SUVmean values at 35-59 min and 60 min post-injection were similar, so 68 Ga-PSMA PET imaging could also be made at 35-59 min post-injection.

Diagnostic value of 18F-FDG PET/CT in patients with biochemical recurrent prostate cancer and negative 68Ga-PSMA PET/CT.

PURPOSE: 68Ga-PSMA PET/CT has a high detection rate in prostate cancer patients with biochemical recurrence (BCR). However, few studies have reported other imaging methods for BCR with negative 68Ga-PSMA PET/CT findings. We investigated the value of 18F-FDG compared with 68Ga-PSMA and identified BCR patients with 68Ga-PSMA-negative findings who are most likely to benefit from 18F-FDG PET/CT. METHODS: Seventy-two BCR patients with negative 68Ga-PSMA PET/CT findings were retrospectively identified from 510 patients who underwent concomitant 68Ga-PSMA and 18F-FDG PET/CT between June 2018 and August 2020. Patients were categorised into groups with positive or negative 18F-FDG PET/CT findings. Differences in patients' characteristics between these two groups and predictors of positive 18F-FDG findings were analysed. RESULTS: The detection rate of 18F-FDG PET/CT was 16.7% (12/72) in BCR patients with 68Ga-PSMA-negative findings. PSA and Gleason score were significantly higher in the 18F-FDG-positive group than in the 18F-FDG-negative group (P < 0.001 and P < 0.001, respectively). A multivariate analysis indicated that PSA (PSA ≥2.3 ng/mL) and Gleason score (Gleason score ≥ 8) correlated with 18F-FDG-positive findings (P < 0.001 and P = 0.015, respectively). The probabilities of 18F-FDG-positive findings in the low-potential (PSA <2.3 ng/mL and Gleason score <8), moderate-potential (PSA <2.3 ng/mL and Gleason score ≥ 8 or PSA ≥2.3 ng/mL and Gleason score <8), and high-potential (PSA ≥2.3 ng/mL and Gleason score ≥ 8) groups were 0%, 11.5%, and 90.0%, respectively (P < 0.001). CONCLUSION: PSA level and Gleason score are independent predictors of 18F-FDG-positive findings, and BCR patients with 68Ga-PSMA-negative findings with high PSA and Gleason score are most likely to benefit from 18F-FDG PET/CT.

Altered Mitochondrial Dynamics, Biogenesis, and Functions in the Paclitaxel-Resistant Lung Adenocarcinoma Cell Line A549/Taxol.

BACKGROUND Chemoresistance is a primary hindrance for current cancer treatments. The influence of abnormal mitochondria in chemotherapy resistance is not well known. To explore the correlation between mitochondria and acquired chemoresistance, this work studied alterations in mitochondrial dynamics, biogenesis, and functions for paclitaxel-resistant cancer cell line A549/Taxol and its parental line A549. MATERIAL AND METHODS Mitochondrial morphology was observed by transmission electron microscopy and confocal microscopy. We measured the mitochondrial mass and mitochondrial membrane potential using fluorescent dyes. The glucose metabolic profile and ATP (adenosine triphosphate) content were determined by bioluminescent cell assays. Seahorse bio-energy analyzer XF24 was used to detect the mitochondrial respiratory function. The expressions of mitochondrial dynamics and biogenesis related genes were quantified using real-time polymerase chain reaction. RESULTS We observed fusion morphology of the mitochondrial network in A549/Taxol cells, with upregulation of fusion genes (Mfn1 and Mfn2) and downregulation of fission gene Fis1. In A549/Taxol cells, mitochondrial mass showed a significant decrease, while the mitochondrial biogenesis pathway was strongly activated. Despite the decreased mitochondrial membrane potential, the capability for mitochondrial respiration was not impaired in A549/Taxol cells. CONCLUSIONS Our study revealed a series changes of mitochondrial characteristics in paclitaxel-resistant cells. Mfn1 and Mfn2 and PGC-1alpha increased, while Fis1 expression and mitochondrial oxidative phosphorylation decreased in A549/Taxol cell lines. These changes to mitochondrial fusion, fission, and biological function contributed to the occurrence of paclitaxel resistance in tumor cells which induced paclitaxel resistance.

Relationship between the expression of PD-1/PD-L1 and 18F-FDG uptake in bladder cancer.

PURPOSE: Immunotherapy aimed at inhibiting the PD-1/PD-L1 immune checkpoint has been approved and used successfully for the treatment of bladder cancer. The identification of markers predictive of response to immune checkpoint inhibitors is critical to advancing the success of this therapy. 18F-FDG PET/CT is a molecular imaging technique that can provide phenotypic information on malignant tumours. It is currently unknown whether there is a relationship between 18F-FDG uptake and expression of PD-1/PD-L1 in bladder cancer. In this study, we investigated whether PD-1/PD-L1 expression is associated with 18F-FDG uptake in bladder cancer, and whether 18F-FDG PET/CT imaging can be used to predict the PD-1/PD-L1 status of bladder cancer. METHODS: A retrospective analysis was performed in 63 patients with bladder cancer who had undergone 18F-FDG PET/CT before surgical resection. Maximum standardized uptake values (SUVmax) were determined. RESULTS: SUVmax was significantly higher in PD-1-positive patients than in PD-1-negative patients (33.0 ± 13.9 and 19.6 ± 14.2, respectively; P = 0.032), and in PD-L1-positive patients than in PD-L1-negative patients (29.1 ± 15.6 and 15.8 ± 11.4, respectively; P < 0.0001). In a multivariate analysis SUVmax was significantly associated with both PD-1 expression and PD-L1 expression (P = 0.021 and P = 0.003, respectively). Using a SUVmax cut-off value of 22.7, PD-1 status and PD-L1 status could be predicted with accuracies of 71.4% and 77.8%, respectively. CONCLUSION: Higher 18F-FDG uptake by bladder cancer is associated with elevated PD-1/PD-L1 expression. 18F-FDG PET/CT may be useful for predicting the PD-1/PD-L1 status of bladder cancer and for determining the optimal therapeutic strategy.

Validity of a Chinese version of the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) and a comparison of completion by patients and relatives.

OBJECTIVE: To test the psychometric properties of the Chinese version of the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) and to investigate the differences between the MiniAQLQ completed by patients (p-MiniAQLQ) and by their relatives (r-MiniAQLQ). METHODS: One hundred and two asthmatic patients and 45 relatives were recruited. The reliability was evaluated using Cronbach's alpha and intraclass correlation coefficient (ICC). The validity of the MiniAQLQ was assessed by comparing it with the Sydney Asthma Quality of Life Questionnaire (AQLQ-S) and lung function measurements. The mean quality of life scores were compared by gender and smoking history, and the p-MiniAQLQ scores were then compared with the r-MiniAQLQ scores. RESULTS: The MiniAQLQ showed high internal consistency (Cronbach's alpha = 0.901) and a high two-week reproducibility (ICC = 0.863). The cross-sectional correlations between the MiniAQLQ and the AQLQ-S were strong. Correlations between the MiniAQLQ and lung function (predicted FEV1% and PEF) ranged from poor to weak at the total or domain levels. The MiniAQLQ scores were not significantly associated with gender or smoking history. There was poor agreement between the p-MiniAQLQ and r-MiniAQLQ scores at the total or domain levels. CONCLUSIONS: The Chinese version of the MiniAQLQ showed good reliability and validity. It is reliable for evaluating the impact of asthma on patients' quality of life. Relatives of the patients did not have a comprehensive grasp of the patients' conditions. Physicians should be cautious when patients' relatives come to the hospital to seek a modified treatment when the patients are not present.

Fructose-1,6-Bisphosphatase 1 Reduces 18F FDG Uptake in Hepatocellular Carcinoma.

Purpose To determine whether fructose 1,6-bisphosphatase 1 (FBP1) expression is associated with fluorine 18 (18F) fluorodeoxyglucose (FDG) accumulation in patients with hepatocellular carcinoma (HCC) and to investigate how FBP1 expression and 18F FDG uptake are related to tumor differentiation grade and metabolism and whether the molecular mechanism involves hypoxia-inducible factor 1-α (HIF1A) transcriptional activity. Materials and Methods This retrospective study was approved by the institutional review board with informed consent. Eighty-five patients with HCC underwent 18F FDG combined positron emission tomography and computed tomography (PET/CT). The relationship between maximum standardized uptake (SUVmax) and expression of FBP1, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) was analyzed with immunohistochemical analysis. In vitro FBP1 overexpression in HCC cells was used to examine the role of FBP1 in tumor metabolism, and its effect on HIF1A transcriptional activity was investigated with quantitative polymerase chain reaction and luciferase reporter assay. Spearman rank correlation was applied to determine the association between FBP1 expression and SUVmax. Results There was an inverse relationship between FBP1 expression and SUVmax (P = .003). SUVmax was higher in patients with poorly differentiated HCC (mean, 6.7 ± 3.6 [standard deviation]) than in those with well- (mean, 2.6 ± 0.7, P < .001) or moderately (mean, 4.1 ± 2.3, P < .001) differentiated HCC. FBP1 expression was significantly lower in patients with poorly differentiated HCC (mean, 0.6 ± 0.2) than in those with well- (mean, 1.4 ± 0.6, P = .006) or moderately (mean, 1.2 ± 0.2, P = .007) differentiated HCC. FBP1 overexpression in HCC cells led to a significant decrease in GLUT1 expression (P = .034), 18F FDG uptake (P = .023), and HIF1A transcriptional activity (P = .001). Conclusion SUVmax in patients with HCC is inversely associated with FBP1 expression, and FBP1 may inhibit 18F FDG uptake via the HIF1A pathway. SUVmax is higher in patients with poorly differentiated HCC than in those with well- or moderately differentiated HCC, which could be the result of lower FBP1 expression in the former. © RSNA, 2017.