Clinical Implementation of Total-Body PET in China.

Total-body (TB) PET/CT is a groundbreaking tool that has brought about a revolution in both clinical application and scientific research. The transformative impact of TB PET/CT in the realms of clinical practice and scientific exploration has been steadily unfolding since its introduction in 2018, with implications for its implementation within the health care landscape of China. TB PET/CT's exceptional sensitivity enables the acquisition of high-quality images in significantly reduced time frames. Clinical applications have underscored its effectiveness across various scenarios, emphasizing the capacity to personalize dosage, scan duration, and image quality to optimize patient outcomes. TB PET/CT's ability to perform dynamic scans with high temporal and spatial resolution and to perform parametric imaging facilitates the exploration of radiotracer biodistribution and kinetic parameters throughout the body. The comprehensive TB coverage offers opportunities to study interconnections among organs, enhancing our understanding of human physiology and pathology. These insights have the potential to benefit applications requiring holistic TB assessments. The standard topics outlined in The Journal of Nuclear Medicine were used to categorized the reviewed articles into 3 sections: current clinical applications, scan protocol design, and advanced topics. This article delves into the bottleneck that impedes the full use of TB PET in China, accompanied by suggested solutions.

A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma.

PURPOSE: To investigate and compare the dynamic positron emission tomography (PET) imaging with [18F]Alfatide II Imaging and [11C]Methionine ([11C]MET) in orthotopic rat models of glioblastoma multiforme (GBM), and to assess the utility of [18F]Alfatide II in detecting and evaluating neoangiogenesis in GBM. METHODS: [18F]Alfatide II and [11C]MET were injected into the orthotopic GBM rat models (n = 20, C6 glioma cells), followed by dynamic PET/MR scans 21 days after surgery of tumor implantation. On the PET image with both radiotracers, the MRI-based volume-of-interest (VOI) was manually delineated encompassing glioblastoma. Time-activity curves were expressed as tumor-to-normal brain ratio (TNR) parameters and PET pharmacokinetic modeling (PKM) performed using 2-tissue-compartment models (2TCM). Immunofluorescent staining (IFS), western blotting and blocking experiment of tumor tissue were performed for the validation. RESULTS: Compared to 11C-MET, [18F]Alfatide II presented a persistent accumulation in the tumor, albeit with a slightly lower SUVmean of 0.79 ± 0.25, and a reduced uptake in the contralateral normal brain tissue, respectively. This resulted in a markedly higher tumor-to-normal brain ratio (TNR) of 18.22 ± 1.91. The time-activity curve (TACs) showed a significant increase in radioactive uptake in tumor tissue, followed by a plateau phase up to 60 min for [18F]Alfatide II (time to peak:255 s) and 40 min for [11C]MET (time to peak:135 s) post injection. PKM confirmed significantly higher K1 (0.23/0.07) and K3 (0.26/0.09) in the tumor region compared to the normal brain with [18F]Alfatide II. Compared to [11C]MET imaging, PKM confirmed both significantly higher K1/K2 (1.24 ± 0.79/1.05 ± 0.39) and K3/K4 (11.93 ± 4.28/3.89 ± 1.29) in the tumor region with [18F]Alfatide II. IFS confirmed significant expression of integrin and tumor vascularization in tumor region. CONCLUSION: [18F]Alfatide II demonstrates potential in imaging tumor-associated neovascularization in the context of glioblastoma multiforme (GBM), suggesting its utility as a tool for further exploration in neovascular characterization.

Metabolic parameters of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography for prognosis in patients with gallbladder adenocarcinoma: a cohort study.

Background: The incidence of gallbladder adenocarcinoma (GBA) is relatively low, yet it exhibits a high degree of malignancy and a significantly low 5-year survival rate. The aim of this study was to investigate the prognostic value of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography {2-[18F]FDG PET} parameters in predicting outcomes for patients with GBA. Methods: In total, 67 patients with GBA who underwent 2-[18F]FDG PET/computed tomography (CT) before treatment were retrospectively analyzed at Chinese PLA General Hospital from January 2012 to June 2022. All patients were diagnosed by pathology, and their baseline characteristics and clinical data were collected. The metabolic PET parameters of the primary and metastatic lesions were measured, including the maximum and average standardized uptake values (SUVs), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The prognostic significance of metabolic parameters and other clinical variables was assessed using Cox proportional hazards regression models. Differences in progression-free survival (PFS) and overall survival (OS) in relation to metabolic parameters were examined using the Kaplan-Meier method. Results: During a median follow-up period of 14.2 months, 43 patients (64.2%) experienced tumor recurrence or progression, and 38 patients (56.7%) died of cancer. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.007), distant metastases (P=0.049), tumor differentiation (P=0.028), surgery (P=0.014), carcinoembryonic antigen (CEA) level (P=0.030), carbohydrate antigen 19-9 (CA19-9) level (P=0.003), TLG (P=0.005), MTV (P<0.001), sum of the TLGs of the primary and metastatic lesions (total TLG, tTLG) (P=0.001), and sum of the MTVs of the primary and metastatic lesions (total MTV, tMTV) (P<0.001) were significant predictors of PFS. In multivariate analysis, MTV was an independent predictor of PFS [hazard ratio (HR) =2.785; 95% confidence interval (CI): 1.204-6.441; P=0.017]. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.027), distant metastases (P=0.036), tumor differentiation (P=0.047), surgery (P=0.002), neutrophil-to-lymphocyte ratio (NLR) (P=0.011), CEA level (P=0.036), CA19-9 level (P<0.001), TLG (P=0.007), MTV (P<0.001), tTLG (P=0.003), and tMTV (P<0.001) were significant predictors of OS. In the multivariate analysis, higher CA19-9 levels >37 U/mL and a greater tMTV (HR =2.961; 95% CI: 1.092-8.024; P=0.033) were predictive of OS. Conclusions: Our study results suggest that pretreatment 2-[18F]FDG PET parameters can not only assist in the diagnosis of patients with GBA but may also serve as predictive factors for the prognosis of these patients and should thus be applied in their treatment.

Potential Added Value of 18F-FDG PET Metabolic Parameters in Predicting Disease Relapse in Type 1 Autoimmune Pancreatitis.

BACKGROUND: The predictive value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters for predicting AIP relapse is currently unknown. This study firstly explored the value of 18F-FDG PET/CT parameters as predictors of type 1 AIP relapse. METHODS: This multicenter retrospective cohort study analyzed 51 patients who received 18F-FDG PET/CT prior to treatment and did not receive maintenance therapy after remission. The study collected baseline characteristics and clinical data and conducted qualitative and semi-quantitative analysis of pancreatic lesions and extrapancreatic organs. The study used three thresholds to select the boundaries of pancreatic lesions to evaluate metabolic parameters, including the maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and tumor-to-normal liver standard uptake value ratio (SUVR). Univariate and multivariate analyses were performed to identify independent predictors and build a recurrence prediction model. The model was internally validated using the bootstrap method and a nomogram was created for clinical application. RESULTS: In the univariable analysis, the relapsed group showed higher levels of SUVmax (6.0 ± 1.6 vs. 5.2 ± 1.1; P = 0.047), SUVR (2.3 [2.0-3.0] vs. 2.0 [1.6-2.4]; P = 0.026), and TLG2.5 (234.5 ± 149.1 vs. 139.6 ± 102.5; P = 0.020) among the 18F-FDG PET metabolic parameters compared to the non-relapsed group. In the multivariable analysis, serum IgG4 (OR, 1.001; 95% CI, 1.000-1.002; P = 0.014) and TLG2.5 (OR, 1.007; 95% CI, 1.002-1.013; P = 0.012) were independent predictors associated with relapse of type 1 AIP. A receiver-operating characteristic curve of the predictive model with these two predictors demonstrated an area under the curve of 0.806. CONCLUSION: 18F-FDG PET/CT metabolic parameters, particularly TLG2.5, are potential predictors for relapse in patients with type 1 AIP. A multiparameter model that includes IgG4 and TLG2.5 can enhance the ability to predict AIP relapse.

Radiomic analysis will add differential diagnostic value of benign and malignant pulmonary nodules: a hybrid imaging study based on [18F]FDG and [18F]FLT PET/CT.

PURPOSE: To investigate the clinical value of radiomic analysis on [18F]FDG and [18F]FLT PET on the differentiation of [18F]FDG-avid benign and malignant pulmonary nodules (PNs). METHODS: Data of 113 patients with inconclusive PNs based on preoperative [18F]FDG PET/CT who underwent additional [18F]FLT PET/CT scans within a week were retrospectively analyzed in the present study. Three methods of analysis including visual analysis, radiomic analysis based on [18F]FDG PET/CT images alone, and radiomic analysis based on dual-tracer PET/CT images were evaluated for differential diagnostic value of benign and malignant PNs. RESULTS: A total of 678 radiomic features were extracted from volumes of interest (VOIs) of 123 PNs. Fourteen valuable features were thereafter selected. Based on a visual analysis of [18F]FDG PET/CT images, the diagnostic accuracy, sensitivity, and specificity were 61.6%, 90%, and 28.8%, respectively. For the test set, the area under the curve (AUC), sensitivity, and specificity of the radiomic models based on [18F]FDG PET/CT plus [18F]FLT signature were equal or better than radiomics based on [18F]FDG PET/CT only (0.838 vs 0.810, 0.778 vs 0.778, 0.750 vs 0.688, respectively). CONCLUSION: Radiomic analysis based on dual-tracer PET/CT images is clinically promising and feasible for the differentiation between benign and malignant PNs. CLINICAL RELEVANCE STATEMENT: Radiomic analysis will add differential diagnostic value of benign and malignant pulmonary nodules: a hybrid imaging study based on [18F]FDG and [18F]FLT PET/CT. KEY POINTS: • Radiomics brings new insights into the differentiation of benign and malignant pulmonary nodules beyond the naked eyes. • Dual-tracer imaging shows the biological behaviors of cancerous cells from different aspects. • Radiomics helps us get to the histological view in a non-invasive approach.

Multiparameter diagnostic model based on 18F-FDG positron emission tomography and serological examination for differentiating focal autoimmune pancreatitis from pancreatic ductal adenocarcinoma.

Background: 18F-fluorodeoxyglucose positron emission tomography-computerized tomography (18F-FDG PET-CT) has demonstrated high sensitivity in the diagnosis of autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC), while also exhibiting the ability to distinguish AIP from PDAC lesions. The objective of this investigation was to assess the efficacy of multiparametric 18F-FDG PET with serological examination for distinguishing focal AIP (f-AIP) from PDAC. Methods: A total of 127 patients (43 with f-AIP and 84 with PDAC) who received 18F-FDG PET-CT before treatment were retrospectively included in the cohort study conducted at two centers, Beijing Friendship Hospital and Chinese PLA General Hospital, from January 2015 to December 2021. The baseline characteristics and clinical data were collected. The metabolism parameters of 18F-FDG PET, including maximum standardized uptake value (SUVmax), tumor-to-normal liver SUV ratio (SUVR), mean SUV (SUVmean), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were evaluated. The area under the receiver operating characteristic (ROC) curve was used to evaluate the differential diagnostic efficacy. The diagnostic efficacy improvement was assessed through the integrated discriminatory improvement (IDI), net reclassification improvement (NRI), and DeLong test. Results: Serum immunoglobulin G4 (IgG4) >280 mg/dL, carbohydrate antigen 19-9 (CA19-9) <85 U/mL, and metabolic parameters differed significantly between patients with f-AID and PDAC. The ROC curve analysis of MTV showed the highest differentiating diagnostic value [sensitivity =0.814, 95% confidence interval (CI): 0.661-0.911; specificity =0.893, 95% CI: 0.802-0.947; area under the curve (AUC) =0.890, 95% CI: 0.820-0.957]. The combined diagnostics model of serum IgG4 >280 mg/dL, CA19-9 <85 U/mL, and MTV resulted in the highest AUC of 0.991 (95% CI: 0.978-1.000; sensitivity =0.953, 95% CI: 0.829-0.992; specificity =0.964, 95% CI: 0.892-0.991). Conclusions: The multiparameter diagnostic model based on 18F-FDG PET and serological examination has excellent clinical value in the differential diagnosis of f-AID and PDAC.

Corrigendum: The role of 18F-FDG PET in predicting the pathological response and prognosis to unresectable HCC patients treated with lenvatinib and PD-1 inhibitors as a conversion therapy.

[This corrects the article DOI: 10.3389/fimmu.2023.1151967.].

18F-FDG-PET/CT-based deep learning model for fully automated prediction of pathological grading for pancreatic ductal adenocarcinoma before surgery.

BACKGROUND: The determination of pathological grading has a guiding significance for the treatment of pancreatic ductal adenocarcinoma (PDAC) patients. However, there is a lack of an accurate and safe method to obtain pathological grading before surgery. The aim of this study is to develop a deep learning (DL) model based on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) for a fully automatic prediction of preoperative pathological grading of pancreatic cancer. METHODS: A total of 370 PDAC patients from January 2016 to September 2021 were collected retrospectively. All patients underwent 18F-FDG-PET/CT examination before surgery and obtained pathological results after surgery. A DL model for pancreatic cancer lesion segmentation was first developed using 100 of these cases and applied to the remaining cases to obtain lesion regions. After that, all patients were divided into training set, validation set, and test set according to the ratio of 5:1:1. A predictive model of pancreatic cancer pathological grade was developed using the features computed from the lesion regions obtained by the lesion segmentation model and key clinical characteristics of the patients. Finally, the stability of the model was verified by sevenfold cross-validation. RESULTS: The Dice score of the developed PET/CT-based tumor segmentation model for PDAC was 0.89. The area under curve (AUC) of the PET/CT-based DL model developed on the basis of the segmentation model was 0.74, with an accuracy, sensitivity, and specificity of 0.72, 0.73, and 0.72, respectively. After integrating key clinical data, the AUC of the model improved to 0.77, with its accuracy, sensitivity, and specificity boosted to 0.75, 0.77, and 0.73, respectively. CONCLUSION: To the best of our knowledge, this is the first deep learning model to end-to-end predict the pathological grading of PDAC in a fully automatic manner, which is expected to improve clinical decision-making.

[Analysis of risk factors for recurrence of differentiated thyroid carcinoma after surgical resection combined with iodine-131 and TSH suppression therapy].

Objective:To investigate the risk factors of recurrence after surgical resection of differentiated thyroid carcinoma combined with iodine-131 and TSH（Thyroid stimulating hormone） inhibition therapy. Methods:From January 2015 to April 2020, the clinical data of patients with structural recurrence and without recurrence were retrospectively collected after surgical treatment combined with iodine-131 and TSH inhibition therapy in the First Medical Center of PLA General Hospital. The general conditions of the two groups of patients were analyzed and the measurement data in line with the normal distribution was used for comparison between groups. For measurement data with non-normal distribution, the rank sum test was used for inter-group comparison. The Chi-square test was used for comparison between the counting data groups. Univariate and multivariate regression analyses were used to determine the risk factors associated with relapse. Results:The median follow-up period was 43 months（range 18-81 months） and 100 patients（10.5%） relapsed among the 955 patients. Univariate analysis showed that tumor size, tumor multiple, the number of lymph node metastases>5 in the central region of the neck, and the number of lymph node metastases>5 in the lateral region were significantly correlated with post-treatment recurrence（P<0.001, P=0.018, P<0.001, P<0.001）. Multivariate analysis showed that tumor size（adjusted odds ratio OR: 1.496, 95%CI: 1.226-1.826, P<0.001）, tumor frequency（adjusted odds ratio OR: 1.927, 95%CI: 1.003-3.701, P=0.049）, the number of lymph node metastases in the central neck region>5（adjusted odds ratio OR: 2.630, 95%CI: 1.509-4.584, P=0.001） and the number of lymph node metastases in the lateral neck region>5（adjusted odds ratio OR: 3.074, 95%CI: 1.649-5.730, P=0.001） was associated with tumor recurrence. Conclusion:The study showed that tumor size, tumor multiple, the number of lymph node metastases in the central region of the neck>5 and the number of lymph node metastases in the side of the neck >5 are independent risk factors for recurrence of differentiated thyroid cancer after surgical resection combined with iodine-131 and TSH inhibition therapy.

The role of 18F-FDG PET in predicting the pathological response and prognosis to unresectable HCC patients treated with lenvatinib and PD-1 inhibitors as a conversion therapy.

Purpose: To investigate the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), as an imaging biomarker, for predicting pathological response and prognosis of unresectable hepatocellular carcinoma (HCC) patients treated with Lenvatinib and programmed cell death protein 1 (PD-1) inhibitors as a conversion therapy. Methods: A total of 28 unresectable HCC patients with BCLC stage B or C were treated with Lenvatinib and PD-1 inhibitors before surgery. The 18F-FDG PET/CT scans were acquired before pre- (scan-1) and post-conversion therapy (scan-2). The maximum standardized uptake value (SUVmax), TLR (tumor-to-normal liver standardized uptake value ratio), and the percentages of post-treatment changes in metabolic parameters (ΔSUVmax [%] and ΔTLR [%]) were calculated. Major pathological response (MPR) was identified based on the residual viable tumor in the resected primary tumor specimen (≤10%). Differences in the progression-free survival (PFS) and overall survival (OS) stratified by ΔTLR were examined by the Kaplan-Meier method. Results: 11 (11/28, 39.3%) patients were considered as MPR responders and 17 (17/28, 60.7%) patients as non-MPR responders after conversion therapy. ΔSUVmax (-70.0 [-78.8, -48.8] vs. -21.7 [-38.8, 5.7], respectively; P<0.001) and ΔTLR (-67.6 [-78.1, -56.8] vs. -18.6 [-27.9, 4.0], respectively; P<0.001) were reduced in the responder group than those in the non-responder group. According to the results of the receiver operating characteristic curve analysis, ΔTLR showed an excellent predictive value for the MPR of primary HCC lesions (area under curve=0.989, with the optimal diagnostic threshold of -46.15). When using ΔTLR of -21.36% as a threshold, patients with ΔTLR-based metabolic response had superior PFS (log-rank test, P=0.001) and OS (log-rank test, P=0.016) compared with those without ΔTLR-based metabolic response. Conclusion: 18F-FDG PET is a valuable tool for predicting pathological response and prognosis of unresectable HCC patients treated by Lenvatinib combined with PD-1 as a conversion therapy.

Can 18F-PSMA-7Q PET/CT replace prostate biopsy for the diagnosis of prostate cancer?-A single-center retrospective study.

Background: Of the currently available prostate-specific membrane antigen (PSMA) positron emission tomography (PET) tracers, although 68Ga-PSMA-11 and 18F-DCFPyL have been approved by the US Food and Drug Administration (FDA), both tracers are excreted rapidly through the urinary tract, resulting in strong accumulation in the bladder and blurring the prostate.18F-PSMA-7Q is a novel quinoline-containing PSMA PET tracer developed by our team, which is primarily excreted through the liver. It can reduce the incidence of urine-induced false-positives in the prostate. We aimed to explore the diagnostic efficacy of 18F-PSMA-7Q PET/computed tomography (CT), and when 18F-PSMA-7Q PET/CT can be used instead of prostate biopsy to diagnose prostate cancer. Methods: Patients who underwent 18F-PSMA-7Q PET/CT for prostate cancer staging or prostate biopsy guidance at our institution between July 2020 and December 2021 were retrospectively enrolled. Molecular imaging PSMA (miPSMA) scores were assigned for intra-prostatic lesions according to the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria, and the diagnostic efficacy of 18F-PSMA-7Q PET/CT for different miPSMA scores was evaluated using pathological diagnosis as the gold standard. Results: Of the 125 enrolled patients, 101 had prostate cancer, and 24 had prostatic hyperplasia or prostatitis. miPSMA ≥2 was the optimal diagnostic threshold, and area under curve (AUC) was 0.948, the sensitivity and specificity were 91.1% and 83.0%. The prostate cancer detection rates of 18F-PSMA-7Q PET/CT were 14.3% (3/21), 60.0% (6/10), 96.7% (58/60), and 100% (34/34) for patients with miPSMA scores of 0, 1, 2, and 3, respectively. There was no significant difference in the detection rate of prostate cancer between groups with miPSMA scores of 2 and 3, but there were significant differences between any other 2 groups. Conclusions: The prostate cancer detection rate of 18F-PSMA-7Q PET/CT was high for lesions with greater miPSMA scores of 2 and 3. For patients with a high miPSMA score, particularly those with a miPSMA score of 3, prostate biopsy can be omitted and prostate cancer-related treatment can be considered.

Multiparameter diagnostic model based on 18F-FDG PET metabolic parameters and clinical variables can differentiate nonmetastatic gallbladder cancer and cholecystitis.

OBJECTIVE: To evaluate the diagnostic value of a multiparameter model based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters and clinical variables in differentiating nonmetastatic gallbladder cancer (GBC) from cholecystitis. PATIENTS AND METHODS: In total, 122 patients (88 GBC nonmetastatic patients and 34 cholecystitis patients) with gallbladder space-occupying lesions who underwent 18F-FDG PET/CT were included. All patients received surgery and pathology, and baseline characteristics and clinical data were also collected. The metabolic parameters of 18F-FDG PET, including SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), SUVpeak (peak standard uptake value), MTV (metabolic tumour volume), TLG (total lesion glycolysis) and SUVR (tumour-to-normal liver standard uptake value ratio), were evaluated. The differential diagnostic efficacy of each independent parameter and multiparameter combination model was evaluated using the receiver operating characteristic (ROC) curve. The improvement in diagnostic efficacy using a combination of the above multiple parameters was evaluated by integrated discriminatory improvement (IDI), net reclassification improvement (NRI) and bootstrap test. Decision curve analysis (DCA) was used to evaluate clinical efficacy. RESULTS: The ROC curve showed that SUVR had the highest diagnostic ability among the 18F-FDG PET metabolic parameters (area under the curve [AUC] = 0.698; sensitivity = 0.341; specificity = 0.971; positive predictive value [PPV] = 0.968; negative predictive value [NPV] = 0.363). The combined diagnostic model of cholecystolithiasis, fever, CEA > 5 ng/ml and SUVR showed an AUC of 0.899 (sensitivity = 0.909, specificity = 0.735, PPV = 0.899, NPV = 0.758). The diagnostic efficiency of the model was improved significantly compared with SUVR. The clinical efficacy of the model was confirmed by DCA. CONCLUSIONS: The multiparameter diagnostic model composed of 18F-FDG PET metabolic parameters (SUVR) and clinical variables, including patient signs (fever), medical history (cholecystolithiasis) and laboratory examination (CEA > 5 ng/ml), has good diagnostic efficacy in the differential diagnosis of nonmetastatic GBC and cholecystitis.

18 F-DCFPyL positron emission tomography/magnetic resonance imaging-guided ultrasound fusion biopsy is an identical pathway in prostate cancer diagnosis.

BACKGROUND: Prostate biopsy is still unavoidable in patients with a rising prostate-specific antigen even though multiparametric magnetic resonance imaging (MRI) is widely used. 18 F-DCFPyL positron emission tomography (PET)/MRI was proved to be promising both in sensitivity and specificity. But its guiding fusion biopsy and the advantages in the diagnosis of prostate disease is seldom reported. This study aimed to verify the feasibility and advantage of 18 F-DCFPyL PET/MRI-guided fusion targeted biopsy (TB) over whole-mount histopathology (WMH) for prostate cancer diagnosis. METHODS: A prospective study of 94 biopsy-naïve patients were conducted using 18 F-DCFPyL PET/MRI scans and scored on a scale of 1-4. Systematic biopsy was performed for all patients. Patients with suspicious lesions also underwent PET/MRI/transrectal ultrasound-guided fusion biopsy. Patients with pathologically confirmed cancer underwent surgery and WMH sections. Systematic biopsy was compared with TB for the detection of index tumors (ITs). Significant cancer was defined as Grade group (GG) 2 or higher no matter the length of the cancer core. RESULTS: 18 F-DCFPyL PET/MRI detected 30/94 (32%) patients with a score of 4, all of whom were verified to have prostate cancer. While it detected 10 patients with a score of 1 (10.6%), they were shown to have no cancer. The sensitivity and specificity of 18 F-DCFPyL PET/MRI were 94.4% and 75%, respectively, if images with a score of 3 are defined as positive. Systematic biopsy detected 18% (203/1128) samples as prostate cancer; conversely, TB detected 113 samples out of 259 scores (43.6%). A statistically significant difference was seen between the PCa detection rates by TB and SB (p < 0.001). All targeted lesions were pathologically proven to be the IT on WMH. CONCLUSIONS: In biopsy-naïve patients, the ultrasound fusion biopsy targeted by 18 F-DCFPyL PET/MRI is an identical pathway for the detection of prostate cancer.

Expert consensus on oncological [18F]FDG total-body PET/CT imaging (version 1).

BACKGROUND: [18F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [18F]FDG TB PET/CT imaging. METHODS: The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners. RESULTS: This consensus describes the protocols for routine and dynamic [18F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies. CONCLUSION: This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging. KEY POINTS: • [18F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.

A Preclinical Study of an 125I-Labeled PSMA Ligand for Prostate-Cancer Puncture.

PURPOSE: Prostate cancer (PCa) is characterized by high expression of prostate-specific 1membrane antigen (PSMA), a type II transmembrane protein. Prostate-specific membrane antigen positron emission tomography (PSMA PET) has high sensitivity and specificity and can therefore be potentially used to detect PCa. Exploiting the advantages of PSMA PET imaging, in this study, we aim to develop a novel radiopharmaceutical to facilitate biopsy punching of PCa. METHODS: We synthesized a high-affinity radiopharmaceutical of PSMA (125I-PSMA-7). We evaluated the properties of 125I-PSMA-7, including the purity, stability, affinity, partition coefficient, and toxicity. (PSMA+) 22Rv1 and (PSMA-) PC3 cell lines were used to evaluate 125I-PSMA-7 in vitro. BALB/c nude mice bearing 22Rv1 and PC3 xenografts were used for biodistribution and imaging. The uptake of the main organs was evaluated in vivo using single photon emission computed tomography (SPECT). RESULTS: 125I-PSMA-7 had a purity of 99.6% and remained stable for seven days and was therefore always safe to use. 125I-PSMA-7 had a Ki of 4.037 × 10-11 and a partition coefficient of -1.80. The results of in vitro cellular experiments showed a high uptake by 22Rv1 cells (ranging from 2.88 ± 0.14 IA%/106 at 5 min to 61.98 ± 3.43 IA%/106 at 24 h, where the internalization was 46.1% at 1 h and 88.06% at 24 h). However, the uptake of PC3 cells was very low (ranging from 0.34 ± 0.08 IA%/106 at 5 min to 1.60 ± 0.15 IA%/106 at 24 h). The tumors' uptake of 125I-PSMA-7 ranged from 9.02 ± 0.30 ID%/g at 1 h to 4.11 ± 1.04 ID%/g at 7 d and the tumor/muscle ratios and tumor/blood ratios increased over time. In addition, we used γ-counter to measure cpm per milligram of tumor and muscle on days 4 and 7. The background on day 4 is 42 cpm and the tumor is 1739 cpm/mg and the muscle is 45 cpm/mg, and the background on day 7 is 74 cpm and the tumor is 1404cpm/mg and the muscle is 32 cpm/mg. At 1 h post-injection, the high uptake of 125I-PSMA-7 resulted in clear delineation of 22Rv1-derived tumors upon imaging. By comparison, 22Rv1-blocking mice took up less 125I-PSMA-7. CONCLUSIONS: These results show that 125I-PSMA-7 is a promising radiotracer that could be used to puncture the prostate. 125I-PSMA-7 could be applied to targeted biopsy, reducing the need for saturated biopsy.

Case Report: A rare case of primary hepatic Castleman's disease mimicking a liver tumor.

Castleman's disease (CD) is a primary lymphoproliferative disorder of the lymph nodes with rare extra-nodal primary affection. Solid organ involvement is rare, and isolated liver involvement is extremely rare. Here we presented a case of a 59-year-old woman with a hepatic lesion accidentally found by ultrasound. The MRI result indicated primary liver malignancy or liver metastases. 18F-FDG PET/CT could not exclude hepatic malignant tumor due to its high metabolism. Finally, the hepatic CD was confirmed by postoperative pathology.

Medication overuse headache associated with decreased dopamine transporter availability in the medial but not in the lateral orbitofrontal cortex: a 11CFT PET/MR study.

BACKGROUNDS: Dysfunction of the mesocorticolimbic dopamine system in medication overuse headache (MOH) is unknown. This study aimed to determine dopamine transporter (DAT) availability, which is sensitive to dopamine levels, in the mesocorticolimbic dopamine system in MOH patients. METHODS: This case-control study investigated eligible MOH patients admitted to the International Headache Centre in the neurological department of Chinese PLA General Hospital between July 2018 and August 2019. All subjects underwent an integrated positron emission tomography (PET)/magnetic resonance (MR) brain scans with 11CFT, a radioligand that binds to DAT. Standardised uptake value ratio (SUVr) images were compared voxelwise between MOH patients and healthy controls (HCs). SUVr values from significantly changed regions were extracted, and partial correlation analyses with clinical measures were conducted. RESULTS: We examined 17 MOH patients and 16 HCs. MOH patients had lower SUVr levels in the medial rather than lateral orbitofrontal cortex (OFC) than HCs (T = -5.0317, PGRF < 0.01), which showed no correlation with clinical features. CONCLUSIONS: MOH is characterised by decreased DAT availability in the medial OFC, which might reflect compensatory downregulation due to low dopamine signalling within the mesocorticolimbic dopamine system and provide a new perspective to understand the pathogenesis of MOH.

Optimized 68Ga-Labeled Urea-Based PSMA-Targeted PET Tracers for Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals have become some of the most promising tools for the diagnosis and therapy prostate cancer (PCa). The structure of existing PSMA-targeted PET tracers still needs to be optimized to improve their pharmacokinetic properties and tumor-to-background ratio. In this study, we modified the structure of a well-studied PSMA tracer, and six novel tracers with variable hydrophilicity and pharmacokinetics were developed and evaluated both in vitro and in vivo. All of the novel tracers showed high hydrophilicity (log p = -2.99 ± 0.33 to -3.49 ± 0.01), rapid clearance rates (elimination half-times = 15.55 to 35.97 min), and high affinity for PSMA (Ki = 8.11 ± 0.49 to 42.40 ± 2.11 nM) in vitro. Specific cell binding and micro-PET experiments showed that [68Ga]Ga-PSMA-Q displayed the highest specific PSMA+ cell uptake (3.75 ± 0.35 IA%/106 at 60 min), tumor uptake (SUVmax = 0.97 ± 0.24 at 60 min p.i.), and tumor-to-muscle ratio (59.33 ± 5.72 at 60 min p.i.), while the tumor-to-muscle ratio was much higher than that of [68Ga]Ga-PSMA-617. The results of this study validate the clinical potential of [68Ga]Ga-PSMA-Q for PET imaging and further targeted therapy of prostate cancer.

Correlation between apparent diffusion coefficient and tumor-stroma ratio in hybrid 18F-FDG PET/MRI: preliminary results of a rectal cancer cohort study.

Background: To explore possible correlations between the tumor-stroma ratio (TSR) and different imaging features of fluorine-18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) in untreated rectal cancer patients. Methods: A patients with rectal cancer were included in this study. All participants were examined preoperatively with whole-body 18F-FDG PET/MRI. Two pathologists evaluated the TSR of tumors together. Apparent diffusion coefficient (ADC) values and PET-related parameters of the primary lesions were measured and compared between the stroma-high and stroma-low groups. Pearson's correlation or Spearman's rank correlation were used to evaluate the correlation between the ADC values, PET-related parameters, and pathological indices. Results: Our results showed that in the untreated rectal cancer patients, the ADC mean values correlated with the TSR (r=0.327; P=0.007), and stroma-high (low TSR) rectal cancer corresponded to relatively lower ADC mean values (813.54±88.68 vs. 879.92±133.18; P=0.018). The ADC mean and ADC minimum (ADCmin) values were found to be negatively correlated with the pathological T stages (r=-0.384, P=0.001; r=-0.416, P=0.001, respectively) as well as the largest tumor diameters (r=-0.340, P=0.005; r=-0.314, P=0.010, respectively) of rectal cancer. In addition, the pathological T stages correlated with all PET-related metabolic parameters, including mean standard uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) (r=0.338, P=0.006; r=0.350, P=0.004; r=0.326, P=0.007; and r=0.472, P<0.001, respectively). Our results also identified associations between the ADCmin values and SUVmean, SUVmax, and TLG (r=-0.335, P=0.006; r=-0.343, P=0.005; and r=-0.343, P=0.005, respectively). However, there were no statistical correlations between the PET/MRI parameters and the immunohistochemical (IHC) results. Conclusions: This study indicated that the intratumoral heterogeneity measured by PET/MRI may reflect characteristics of the tumor microenvironment. Hence, PET/MRI parameters might be helpful in predicting tumor aggressiveness and prognosis.

Pretreatment Metabolic Parameters Measured by 18F-FDG PET to Predict the Pathological Treatment Response of HCC Patients Treated With PD-1 Inhibitors and Lenvatinib as a Conversion Therapy in BCLC Stage C.

Objectives: This study aimed to assess the pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) as a predictor of the pathological treatment response (PTR) of hepatocellular carcinoma (HCC) patients treated with PD-1 inhibitors and lenvatinib as a conversion therapy in BCLC stage C. Methods: All patients (n=20) underwent pretreatment 18F-FDG PET/CT and were treated with conversion therapy and surgery. Patients were categorized into responders (n=9) and non-responders (n=11) according to PTR. The parameters of PET/CT, including lesion size, SUVmean (mean standard uptake value), MTV (metabolic tumor volume), TLG (total lesion glycolysis), SUVpeak (peak standard uptake value), and TLR (tumor-to-normal liver standardized uptake value ratio), were calculated. The diagnostic efficacy was evaluated by receiver operating characteristic analysis (ROC). PTR was compared with pretreatment PET/CT parameters by using Spearman correlation analysis. The patients were followed up. Results: There was significant difference in TLR (5.59 ± 1.90 vs. 2.84 ± 1.70, respectively; P=0.003) between responders and non-responders, with the largest area under the curve (sensitivity=100%, specificity=72.7%, AUC=0.899, 95%CI: 0.759-1.000, optimal diagnostic threshold of 3.09). The relationship between 18F-FDG PET/CT parameters and PTR indicated TLR was moderately and positively correlated with pathological treatment response, with correlation coefficients (rs) of 0.69 (P<0.01). During the follow-up, no patients died, and tumor recurrence was found in one of the responders (11.1%). In all 11 non-responders, tumor recurrence was found in six patients (54.5%) and four patients (36.4%) died. Conclusions: TLR may be a powerful marker to predict PTR of HCC patients with BCLC stage C who were treated with conversion therapy.