Dynamic total-body PET/CT imaging with reduced acquisition time shows acceptable performance in quantification of [18F]FDG tumor kinetic metrics.

PURPOSE: To investigate the feasibility of reducing the acquisition time for continuous dynamic positron emission tomography (PET) while retaining acceptable performance in quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) in tumors. METHODS: In total, 78 oncological patients underwent total-body dynamic PET imaging for ≥ 60 min, with 8, 20, and 50 patients receiving full activity (3.7 MBq/kg), half activity (1.85 MBq/kg), and ultra-low activity (0.37 MBq/kg) of [18F]FDG, respectively. The dynamic data were divided into 21-, 30-, 45- and ≥ 60-min groups. The kinetic analysis involved model fitting to derive constant rates (VB, K1 to k3, and Ki) for both tumors and normal tissues, using both reversible and irreversible two-tissue-compartment models. One-way ANOVA with repeated measures or the Freidman test compared the kinetic metrics among groups, while the Deming regression assessed the correlation of kinetic metrics among groups. RESULTS: All kinetic metrics in the 30-min and 45-min groups were statistically comparable to those in the ≥ 60-min group. The relative differences between the 30-min and ≥ 60-min groups ranged from 12.3% ± 15.1% for K1 to 29.8% ± 30.0% for VB, and those between the 45-min and ≥ 60-min groups ranged from 7.5% ± 8.7% for Ki to 24.0% ± 24.3% for VB. However, this comparability was not observed between the 21-min and ≥ 60-min groups. The significance trend of these comparisons remained consistent across different models (reversible or irreversible), administrated activity levels, and partial volume corrections for lesions. Significant correlations in tumor kinetic metrics were identified between the 30-/45-min and ≥ 60-min groups, with Deming regression slopes > 0.813. In addition, the comparability of kinetic metrics between the 30-min and ≥ 60-min groups were established for normal tissues. CONCLUSION: The acquisition time for dynamic PET imaging can be reduced to 30 min without compromising the ability to reveal tumor kinetic metrics of [18F]FDG, using the total-body PET/CT system.

Total-body dynamic PET/CT imaging reveals kinetic distribution of [13N]NH3 in normal organs.

PURPOSE: To systematically investigate kinetic metrics and metabolic trapping of [13N]NH3 in organs. METHODS: Eleven participants performed total-body [13N]NH3 dynamic positron emission tomography (PET). Regions of interest were drawn in organs to obtain time-to-activity curves (TACs), which were fitted with an irreversible two-tissue compartment model (2TC) to investigate constant rates K1, k2 and k3, and to calculate Ki. Additionally, one-tissue compartment model using full data (1TCfull) and the first four minutes of data (1TC4min) were fitted to TAC data. K1 and k2 were compared among different models to assess [13N]NH3 trapping in organs. RESULTS: Kinetic rates of [13N]NH3 varied significantly among organs. The mean K1 ranged from 0.049 mL/cm3/min in the muscle to 2.936 mL/cm3/min in the kidney. The k2 and k3 were lowest in the liver (0.001 min- 1) and in the pituitary (0.009 min- 1), while highest in the kidney (0.587 min- 1) and in the liver (0.800 min- 1), respectively. The Ki was largest in the myocardium (0.601 ± 0.259 mL/cm3/min) while smallest in the bone marrow (0.028 ± 0.022 mL/cm3/min). Three groups of organs with similar kinetic characteristics were revealed: (1) the thyroid, the lung, the spleen, the pancreas, and the kidney; (2) the liver and the muscle; and (3) the cortex, the white matter, the cerebellum, the pituitary, the parotid, the submandibular gland, the myocardium, the bone, and the bone marrow. Obvious k3 was identified in multiple organs, and significant changes of K1 in multiple organs and k2 in most organs were found between 2TC and 1TCfull, but both K1 and k2 were comparable between 2TC and 1TC4min. CONCLUSION: The kinetic rates of [13N]NH3 differed among organs with some have obvious 13N-anmmonia trapping. The normal distribution of kinetic metrics of 13N-anmmonia in organs can serve as a reference for its potential use in tumor imaging.

Circ-MBOAT2 Regulates Angiogenesis via the miR-495/NOTCH1 Axis and Associates with Myocardial Perfusion in Patients with Coronary Chronic Total Occlusion.

Revascularization of coronary chronic total occlusion (CTO) still remains controversial. The factors that impact collateral circulation and myocardial perfusion are of interest. Circular RNA (circRNA) has been shown to regulate the process of angiogenesis. However, the effects of circ-membrane-bound O-acyltransferase domain containing 2 (circ-MBOAT2) on angiogenesis in patients with CTO were unclear. In this study, we evaluated circulating circRNAs and miRNAs in patients with CTO and stable coronary artery disease using high-throughput sequencing. Another cohort of patients were selected to verify the expressions of circ-MBOAT2 and miR-495. The role and mechanism of circ-MBOAT2 in the process of angiogenesis were explored through in vitro and vivo studies. Finally, we came back to a clinical perspective and investigated whether circ-MBOAT2 and miR-495 were associated with the improvement of myocardial perfusion evaluated by single-photon emission computed tomography (SPECT). We found that the expression of circ-MBOAT2 was significantly up-regulated while miR-495 was significantly down-regulated in patients with CTO. The expression of circ-MBOAT2 was negatively correlated with miR-495 in patients with CTO. In an in vitro study, we found that circ-MBOAT2 promoted tube formation and cell migration via the miR-495/NOTCH1 axis in endothelial cells. In an in vivo study, we showed that the inhibition of miR-495 caused the increase in collateral formation in mice after hindlimb ischemia. In a human study, we showed the expressions of circ-MBOAT2 and miR-495 were associated with myocardial perfusion improvement after revascularization of CTO. In conclusion, circ-MBOAT2 regulates angiogenesis via the miR-495/NOTCH1 axis and associates with myocardial perfusion in patients with CTO. Our findings suggest that circ-MBOAT2 and miR-495 may be potential therapeutic targets and prognostic factors for patients with CTO.

Development and Validation of PET/CT-Based Nomogram for Preoperative Prediction of Lymph Node Status in Esophageal Squamous Cell Carcinoma.

PURPOSE: This study was conducted to predict the lymph node status and survival of esophageal squamous cell carcinoma before treatment by PET-CT-related parameters. METHODS: From January 2013 to July 2018, patients with pathologically diagnosed ESCC at our hospital were retrospectively enrolled. Completed esophagectomy and two- or three-field lymph node dissections were conducted. Those with neoadjuvant therapy were excluded. The first 65% of patients in each year were regarded as the training set and the last 35% as the test set. Nomogram was constructed by the "rms" package. Five-year, overall survival was analyzed based on the best cutoff value of risk score determined by the "survivalROC" package. RESULTS: Ultimately, 311 patients were included with 209 in the training set and 102 in the test set. The positive rate of the lymph node in the training set was 36.8% and that in the test set was 32.4%. The C-index of the training set was 0.763 and the test set was 0.766. The decision curve analysis showed that it was superior to the previous methods based on lymph node uptake or long/short axis diameter or axial ratio. Risk score > 0.20 was significantly associated with 5-year, overall survival (p = 0.0015) in all patients. CONCLUSIONS: The nomogram constructed from PET-CT parameters including primary tumor metabolic length and thickness can accurately predict the risk of lymph node metastasis in ESCC. The risk score calculated by our model accurately predicts the patient's 5-year overall survival.

One-stop [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 total-body PET/CT examination with dual-low activity: a feasibility study.

PURPOSE: Positron emission tomography/computed tomography (PET/CT) based on fibroblast activation protein inhibitors (FAPI) has shown complementary values to 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) in cancer imaging. This study aimed to investigate the feasibility of a one-stop FDG-FAPI dual-tracer imaging protocol with dual-low activity for oncological imaging. METHODS: Nineteen patients with malignancies underwent one-stop [18F]FDG (0.37 MBq/kg) PET (PETFDG) and dual-tracer PET 30-40 and 50-60 min (hereafter, PETD30-40 and PETD50-60, respectively) after additional injection of [68Ga]Ga-DOTA-FAPI-04 (0.925 MBq/kg), with a single diagnostic CT to generate the PET/CT. The lesion detection rate and tumor-to-normal ratios (TNRs) of tracer uptake were compared between PETFDG/CT and PETD50-60/CT and between PETD50-60/CT and PETD30-40/CT. In addition, a visual scoring system was established to compare the lesion detectability. RESULTS: The dual-tracer PETD50-60 and PETD30-40/CT showed similar performance in detecting primary tumors but presented significantly higher lesion TNRs than PETFDG. Significantly, more metastases with higher TNRs were identified on PETD50-60 than PETFDG (491 vs. 261, P < 0.001). The dual-tracer PETD50-60 received significantly higher visual scores than single PETFDG (111 vs. 10) in demonstrating both primary tumors (12 vs. 2) and metastases (99 vs. 8). However, these differences were not significant between PETD50-60 and PETD30-40. These resulted in tumor upstaging in 44.4% patients taking PET/CT for initial assessment, and more recurrences (68 vs. 7) were identified in patients taking PET/CT for restaging, both on PETD50-60 and PETD30-40, compared to PETFDG. The reduced effective dosimetry per patient (26.2 ± 2.57 mSv) was equal to that of a single standard whole-body PET/CT. CONCLUSION: The one-stop dual-tracer dual-low-activity PET imaging protocol combines the strengths of [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 with shorter duration and lesser radiation and is thus clinically applicable.

Respiratory-gated PET imaging with reduced acquisition time for suspect malignancies: the first experience in application of total-body PET/CT.

OBJECTIVES: This study aimed to investigate the performance of respiratory-gating imaging with reduced acquisition time using the total-body positron emission tomography/computed tomography (PET/CT) scanner. METHODS: Imaging data of 71 patients with suspect malignancies who underwent total-body 2-[18F]-fluoro-2-deoxy-D-glucose PET/CT for 15 min with respiration recorded were analyzed. For each examination, four reconstructions were performed: Ungated-15, using all coincidences; Ungated-5, using data of the first 5 min; Gated-15 using all coincidences but with respiratory gating; and Gated-6 using data of the first 6 min with respiratory gating. Lesions were quantified and image quality was evaluated; both were compared between the four image sets. RESULTS: A total of 390 lesions were found in the thorax and upper abdomen. Lesion detectability was significantly higher in gated-15 (97.2%) than in ungated-15 (93.6%, p = 0.001) and ungated-5 (92.3%, p = 0.001), but comparable to Gated-6 (95.9%, p = 0.993). A total of 131 lesions were selected for quantitative analyses. Lesions in Gated-15 presented significantly larger standardized uptake values, tumor-to-liver ratio, and tumor-to-blood ratio, but smaller metabolic tumor volume, compared to those in Ungated-15 and Ungated-5 (all p < 0.001). These differences were more obvious in small lesions and in lesions from sites other than mediastinum/retroperitoneum. However, these indices were not significantly different between Gated-15 and Gated-6. Higher, but acceptable, image noise was identified in gated images than in ungated images. CONCLUSIONS: Respiratory-gating imaging with reduced scanning time using the total-body PET/CT scanner is superior to ungated imaging and can be used in the clinic. KEY POINTS: • In PET imaging, respiratory gating can improve lesion presentation and detectability but requires longer imaging time. • This single-center study showed that the total-body PET scanner allows respiratory-gated imaging with reduced and clinically acceptable scanning time.

Ultralow-dose [18F]FDG PET/CT imaging: demonstration of feasibility in dynamic and static images.

OBJECTIVES: Validation of [18F]FDG PET/CT at ultralow-dose (0.37 MBq/kg) and compared to imaging at half-dose (1.85 MBq/kg). METHODS: This prospective head-to-head intraindividual study compared dynamic and static parameters of ultralow-dose with half-dose [18F]FDG total-body PET/CT. In static imaging, the ultralow-dose groups of PET images were denoted ULD5, 60-65 min; ULD8, 60-68 min; ULD10, 60-70 min; and ULD15, 60-75 min. The half-dose group images were reconstructed to 60-61, 60-62, 60-63, and 60-75 min, defined as LD1, LD2, LD3, and LD15, respectively. A 5-point Likert scale was used to subjectively evaluate the quality of static PET images, with a score greater than 3 considered to meet the requirements for clinical diagnosis. RESULTS: Thirty participants were included in this study, and in terms of kinetic indicators, no special differences were found between the two groups of normal organs and lesions. In static images, those in groups ULD8 and LD2 achieved scores of [Formula: see text] 3.0, meeting the requirements for clinical diagnosis. In static imaging, four lesions were missed in the LD1 group with a lesion detectability of 89.7% (35/39). In the meantime, lesions were not missed in the whole ultra-low dose group (ULD5, ULD8, ULD10, and ULD15) and half-dose groups (LD2 and LD3). CONCLUSIONS: Compared with half-dose imaging, ultralow-dose [18F]FDG total-body PET/CT imaging is clinically feasible, and there was no meaningful difference between the two groups of quantitative and qualitative analysis either dynamic or static images. Total-body PET/CT with ultralow-dose activity, the corresponding acquisition time of 8 min provides acceptable image quality and lesion detection. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR2000036487 KEY POINTS: • A prospective single-center study showed that the total-body PET scanner allows ultralow-dose [18F]FDG imaging with acceptable image quality and lesion detectability. • For the participant, radiation exposure can be reduced with ultralow-dose [18F]FDG total-body PET/CT imaging.

Noninvasive Evaluation of EGFR Expression of Digestive Tumors Using 99mTc-MAG3-Cet-F(ab')2-Based SPECT/CT Imaging.

Purpose: This study is aimed at investigating the feasibility of cetuximab (Cet) F(ab')2 fragment- (Cet-F(ab')2-) based single photon emission tomography/computed tomography (SPECT/CT) for assessing the epidermal growth factor receptor (EGFR) expression in digestive tumor mouse models. Methods: Cet-F(ab')2 was synthesized using immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) protease and purified with protein A beads. The product and its in vitro stability in normal saline and 1% bovine serum albumin were analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The EGFR expression in the human colon tumor cell line HT29 and the human stomach tumor cell line MGC803 were verified using western blotting and immunocytochemistry. Cet-F(ab')2 was conjugated with 5(6)-carboxytetramethylrhodamine succinimidyl ester to demonstrate its binding ability to the MGC803 and HT29 cells. Cet-F(ab')2 was conjugated with NHS-MAG3 for 99mTc radiolabeling. The best imaging time was determined using a biodistribution assay at 1, 4, 16, and 24 h after injection of the 99mTc-MAG3-Cet-F(ab')2 tracer. Furthermore, 99mTc-MAG3-Cet-F(ab')2 SPECT/CT was performed on MGC803 and HT29 tumor-bearing nude mice. Results: HT29 cells had low EGFR expression while MGC803 cell exhibited the high EGFR expression. Cet-F(ab')2 and intact cetuximab showed similar high binding ability to MGC803 cells but not to HT29 cells. Cet-F(ab')2 and 99mTc-MAG3-Cet-F(ab')2 showed excellent in vitro stability. The biodistribution assay showed that the target to nontarget ratio was the highest at 16 h (17.29 ± 5.72, n = 4) after tracer injection. The 99mTc-MAG3-Cet-F(ab')2-based SPECT/CT imaging revealed rapid and sustained tracer uptake in MGC803 tumors rather than in HT29 tumors with high image contrast, which was consistent with the results in vitro. Conclusion: SPECT/CT imaging using 99mTc-MAG3-Cet-F(ab')2 enables the evaluation of the EGFR expression in murine EGFR-positive tumors, indicating the potential utility for noninvasive evaluation of the EGFR expression in tumors.

Diagnostic performance of total-body 18F-FDG PET/CT with fast 2-min acquisition for liver tumours: comparison with conventional PET/CT.

PURPOSE: To comparatively evaluate the diagnostic performances of total-body 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) with fast 2-min acquisition and conventional PET/CT in liver cancer patients. METHODS: This study included 156 patients with liver tumours. Seventy-eight patients underwent total-body PET/CT. PET raw data were reconstructed using acquisition durations of 2 min (G2) and 15 min (G15). Another 78 patients with liver lesions (control patients) underwent conventional uMI780 PET/CT (G780). All patients were evaluated based on TNM staging. The maximum tumour standardized uptake value (tumour SUVmax), mean normal liver SUV (SUVmean), and tumour SUVmax-to-liver SUVmean ratio (TLR) were determined for all patients. G15 data were used as the reference in the lesion detectability analysis. The diagnostic performances of PET/CT in terms of visual parameters and of PET in terms of semi-quantitative parameters such as SUVmax and TLR were evaluated. Receiver operating characteristics (ROC) curve analysis of SUVmax and TLR at G2 was performed. Pathologic findings of surgical specimens served as the gold standard for all patients. RESULTS: The lesions found in G15 were also noted in G2; three lymph nodes were missed in G2. However, no significant difference was found in the TNM stage among G2, G15, and G780. For benign and malignant lesions, the liver SUVmean in G2 and G15 was higher than that in G780 (all P < 0.05). The tumour SUVmax and TLR in G2 were equivalent to those in G15 and G780 regardless of whether the lesions were benign or malignant. ROC curve analysis (SUVmax cutoff: 4.34, TLR cutoff: 1.34) demonstrated that G2 also had good sensitivity in detecting liver cancer. CONCLUSION: The diagnostic performance of total-body PET/CT in G2 was comparable to that in G15 among liver cancer patients. Further, the diagnostic efficiency of total-body PET/CT imaging with fast 2-min acquisition and conventional PET/CT was similar.

Ultrafast 30-s total-body PET/CT scan: a preliminary study.

PURPOSE: The aim of this study is to explore the diagnostic value of the images obtained in ultrafast 30-s acquisition time by the total-body PET/CT (18F-FDG injection dose of about 3.7 MBq/kg), and to evaluate whether they can meet the requirements of clinical diagnosis or not. METHODS: This retrospective study explored the clinical value of ultrafast 30-s 18F-FDG total-body PET/CT in 88 oncology patients, using the post-surgical pathological diagnosis as the reference standard. The data were acquired over 300 s and reconstructed using all 300-s data (G300) and only the initial 30 s (G30). Two readers independently assessed all images qualitatively and quantitatively. The diagnostic performance was compared between G300 and G30. RESULTS: The G300 average qualitative score was higher than G30 (P < 0.001). G300 and G30 also differed quantitatively in the liver and mediastinum SUVmax, SD, and SNR (all P < 0.001), but had similar sensitivities (89.09% vs. 86.36%, P = 0.250). The G300 group had higher accuracy (79.73%) and a larger area under the curve (0.709) than G30 (77.70% and 0.695, respectively; all P > 0.05). CONCLUSION: The 30-s total-body PET/CT could meet clinical diagnostic requirements for malignant tumors in patients intolerant to prolonged horizontal positioning.

Short-time total-body dynamic PET imaging performance in quantifying the kinetic metrics of 18F-FDG in healthy volunteers.

PURPOSE: To investigate the performance of short-time dynamic imaging in quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG). METHODS: Dynamic total-body positron emission tomography (PET) imaging was performed in 11 healthy volunteers for 75 min. The data were divided into 30-, 45- and 75-min groups. Nonlinear regression (NLR) generated constant rates (k1 to k3) and NLR-based Ki in various organs. The Patlak method calculated parametric Ki images to generate Patlak-based Ki values. Paired samples t-test or the Wilcoxon signed-rank test compared the kinetic metrics between the groups, depending on data normality. Deming regression and Bland-Altman analysis assessed the correlation and agreement between NLR- and Patlak-based Ki. A two-sided P < 0.05 was considered statistically significant. RESULTS: The 45- and 75-min groups were similar in NLR-based kinetic metrics. The relative difference ranges were as follows: k1, from 3.4% (P = 0.627) in the spleen to 57.9% (P = 0.130) in the white matter; k2, from 6.0% (P = 0.904) in the spleen to 60.7% (P = 0.235) in the left ventricle (LV) myocardium; k3, from 45.6% (P = 0.302) in the LV myocardium to 96.3% (P = 0.478) in the liver; Ki, from 14.0% (P = 0.488) in the liver to 77.8% (P = 0.067) in the kidney. Patlak-based Ki values were also similar between these groups in all organs, except the grey matter (9.6%, P = 0.029) and cerebellum (14.4%, P = 0.002). However, significant differences in kinetic metrics were found between the 30-min and 75-min groups in most organs both in NLR- and Patlak-based analyses. The NLR- and Patlak-based Ki values significantly correlated, with no bias in any of the organs. CONCLUSION: Dynamic imaging using a high-sensitivity total-body PET scanner for a shorter time of 45 min could achieve relevant kinetic metrics of 18F-FDG as done by long-time imaging.

Investigating ultra-low-dose total-body [18F]-FDG PET/CT in colorectal cancer: initial experience.

PURPOSE: This study was to evaluate the effects of an ultra-low dose of [18F]-FDG on the image quality of total-body PET/CT and its lesion detectability in colorectal cancer (CRC). METHODS: Sixty-two CRC patients who underwent total-body PET/CT (uEXPLORER, United Imaging Healthcare, Shanghai, China) with an ultra-low dose (0.37 MBq/kg) of [18F]-FDG were enrolled in this retrospective study. The PET images were reconstructed with the entire 15-min dataset first and then split into 13-, 8-, 5-, 4-, 3-, 2-, and 1-min duration groups to simulate fast scanning images. For simplicity, the images reconstructed with the data from 15 to 1 min were referred to as G15, G13, and so on until G1. Subjective image quality was assessed with 5-point Likert scales. The objective image quality parameters included the SUVmax, SUVmean, and signal-to-noise ratio (SNR) of the liver and blood pool and the SUVmax and tumor-to-background ratio (TBR) of the lesions. G15 served as the control to evaluate lesion detectability. RESULTS: A total of 62 patients (43 men, 19 women; age 41-88, mean ± SD 64.0 ± 10.9 years) with 64 CRC primary tumor lesions and 10 low-grade intraepithelial neoplasia (LGIN) lesions were enrolled in this study. The subjective scores were highest for G15 (4.5 ± 0.5) and then decreased from G13 (4.3 ± 0.4) to G8 (3.7 ± 0.5). The liver SNR increased with the extension of acquisition time from G8 (17.2 ± 2.8) to G13 (20.6 ± 3.4) and G15 (21.9 ± 3.4). The liver SNR of G8 was not significantly different from that of G13 (p = 0.15) and was significantly different from that of G15 (p = 0.001). All 64 CRC lesions could be identified in all image groups, even on G1. One of ten LGINs was missed on G1, G2, and G3, and one LGIN was missed on G1, G2, G3, and G4. G15 served as the control, and 100% (48/48) lymph nodes could be found on G13 and G8 compared to 93.8% (45/48) lymph nodes on G5 and G4, 85.4% (41/48) lymph nodes on G3, 81.3% (39/48) lymph nodes on G2, and 77.1% (37/48) lymph nodes on G1. For liver metastases, there were no missed liver lesions on G13 and G8 and 3, 4, 6, 7, and 9 missed liver lesions on G5, G4, G3, G2, and G1, respectively. For other areas of metastasis, including the lung, peritoneum, and ovaries, there were no missed lesions in any group. CONCLUSIONS: Total-body PET/CT with an ultra-low dose of [18F]-FDG can maintain satisfactory image quality and lesion detectability in CRC.

Kinetic metrics of 18F-FDG in normal human organs identified by systematic dynamic total-body positron emission tomography.

PURPOSE: To investigate the kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in normal organs by using dynamic total-body (TB) positron emission tomography (PET). METHODS: Dynamic TB-PET was performed for nine healthy volunteers. Time-to-activity curves (TACs) were obtained by drawing regions of interest in the organs. A two-tissue compartment model was fitted for each tissue TAC. Constant rates, including k1, k2, and k3, and the metabolic rate of FDG (MRFDG) were obtained. The parameter statistics, including the average, standard deviation, coefficient of variance, and inter-site and inter-individual variances, were compared. RESULTS: Constant rates and MRFDG varied significantly among organs and subjects, but not among sides or sub-regions within an organ. The mean k1 and k2 ranged from 0.0158 min-1 in the right lower lung to 1.1883 min-1 in the anterior wall of the left ventricle (LV) myocardium and from 0.1116 min-1 in the left parietal white matter to 4.6272 min-1 in the left thyroid, respectively. The k3 was lowest in the right upper area of the liver and highest in the septal wall of the LV myocardium. Mean MRFDG ranged from 23.1696 µmol/100 g/min in the parietal cortex to 0.5945 µmol/100 g/min in the lung. Four groups of organs with similar kinetic characteristics were identified: (1) the cerebral white matter, lung, liver, muscle, bone, and bone marrow; (2) cerebral and cerebellar cortex; (3) LV myocardium and thyroid; and (4) pancreas, spleen, and kidney. CONCLUSION: The kinetic rates and MRFDG significantly differed among organs. The kinetic metrics of FDG parameters in normal organs can serve as a reference for future dynamic PET imaging and research.

Ultra-low-activity total-body dynamic PET imaging allows equal performance to full-activity PET imaging for investigating kinetic metrics of 18F-FDG in healthy volunteers.

PURPOSE: To investigate the feasibility of ultra-low-activity total-body positron emission tomography (PET) dynamic imaging for quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in normal organs and to verify its clinical relevance with full-activity imaging. METHODS: Dynamic total-body PET imaging was performed in 20 healthy volunteers, with eight using full activity (3.7 MBq/kg) of 18F-FDG and 12 using 10× activity reduction (0.37 MBq/kg). Image contrast, in terms of liver-to-muscle ratio (LMR), liver-to-blood ratio (LBR), and blood-to-muscle ratio (BMR) of radioactivity concentrations were assessed. A two-tissue compartment model was fitted to the time-to-activity curves in organs based on regions of interest (ROIs) delineation using PMOD, and constant rates (k1, k2, and k3) were generated. Kinetic constants, corresponding coefficients of variance (CoVs), image contrast, radiation dose, prompt counts, and data size were compared between full- and low-activity groups. RESULTS: All constant rates, corresponding CoVs, and image contrast in different organs were comparable with none significant differences between full- and ultra-low-activity groups. PET images in the ultra-low-activity group generated significantly lower effective radiation dose (median, 0.419 vs. 4.886 mSv, P < 0.001), reduced prompt counts (median, 2.79 vs. 55.68 billion, P < 0.001), and smaller data size (median, 71.11 vs. 723.18 GB, P < 0.001). CONCLUSION: Total-body dynamic PET imaging using 10× reduction of injected activity could achieve relevant kinetic metrics of 18F-FDG and comparable image contrast with full-activity imaging. Activity reduction results in significant decrease of radiation dose and data size, rendering it more acceptable and easier for data reconstruction, transmission, and storage for clinical practice.

Can the BMI-based dose regimen be used to reduce injection activity and to obtain a constant image quality in oncological patients by 18F-FDG total-body PET/CT imaging?

PURPOSE: PET image quality is influenced by the patient size according to the current guideline. The study aimed to propose an optimized dose regimen to yield a constant image quality independent of patient habitus to meet the clinical needs. METHODS: A first patient cohort of 78 consecutive oncological patients (59.7 ± 13.7 years) who underwent a total-body PET/CT scan were retrospectively enrolled to develop the regimen. The patients were randomly distributed in four body mass index (BMI) groups according to the World Health Organization (WHO) criteria. The liver SNR (signal-to-noise ratio, SNRL) was obtained by manually drawing regions of interest (ROIs) and normalized (SNRnorm) by the product of injected activity and acquisition time. Fits of SNRnorm against different patient-dependent parameters were performed to determine the best correlating parameter and fit method. A qualitative assessment on image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL. Thus, an optimized regimen was proposed and validated by a second patient cohort consisted of prospectively enrolled 38 oncological patients. RESULTS: The linear fit showed SNRnorm had the strongest correlation (R2 = 0.69) with the BMI than other patient-dependent parameters and fit method. The qualitative assessment indicated a SNRL value of 14.0 as an acceptable threshold to achieve sufficient image quality. The optimized dose regimen was determined as a quadratic relation with BMI: injected activity (MBq) = 39.2 (MBq)/(- 0.03*BMI + 1.49)2. In the validation study, the SNRL no longer decreased with the increase of BMI. There was no significant difference of the image quality regarding the value of SNRL between different BMI groups (p > 0.05). In addition, the injected activity was reduced by 75.6 ± 2.9%, 72.1 ± 4.0%, 67.1 ± 4.4%, and 64.8 ± 3.5% compared with the first cohort for the four BMI groups, respectively. CONCLUSION: The study proposed a quadratic relation between the 18F-FDG injected activity and the patient's BMI for total-body 18F-FDG PET imaging. In this regimen, the image quality can maintain in a constant level independent of patient habitus and meet the clinical requirement with a reduced injected activity.

Relative metabolic tumor burden is associated with residual lymph node status after neoadjuvant chemoradiotherapy in locally advanced esophageal cancer.

BACKGROUND: Extended lymph node involvement could indicate limited survival benefit from neoadjuvant chemoradiotherapy with surgery in resectable locally advanced esophageal cancer. However, the threshold of node involvement is unclear. METHODS: We retrospectively measured and calculated metabolic parameters derived from 18F-FDG PET/CT of the patients with nCRT and surgery. The parameters included metabolic tumor volume of the whole body (MTVwb), of the primary tumor (MTVp), of the lymph nodes (MTVn), and relative metabolic tumor burden (R-MTB, defined as the ratio of MTVwb and MTVp). RESULTS: A total of 67 patients were enrolled in the study. The MTVp with thresholds as 3.0, 3.5, 4.0, 4.5 and 5.0 were significantly correlated with clinical T categories (Spearman's rank correlation coefficient, all P < 0.0001) and clinical tumor length categories (Spearman's rank correlation coefficient, all P ≤ 0.005). However, the MTVn were marginally correlated with clinical lymph node categories (P = 0.023). Among the 31 (31/67, 46.3%) patients with MTVn as 0 (R-MTB as 100.00%), 5 (5/5, 100.0%) were initially restaged as cLym- (MTVn as 0, R-MTB as 100.00%), while 26 (26/62, 41.9%) were initially restaged as cLym + (MTVn > 0, R-MTB > 100.00%). After nCRT, 43 (64.2%) patients achieved ypN0. The univariate and multivariate regression revealed that R-MTB (≤ 106.00% vs. > 106.00%) was an independent factor associated with ypN + status (OR 0.093, 95%CI 0.023-0.378, P = 0.001). CONCLUSION: The preliminary study revealed a great heterogeneity in clinical lymph node categories in esophageal cancer. It suggested that R-MTB was significantly associated with ypN status after neoadjuvant chemoradiotherapy in locally advanced esophageal cancer. The findings with the indications needed to be further studied in a prospective study with a large patient cohort.

Volumetric parameters on 18F-FDG PET/CT predict the survival of patients with gastric cancer associated with their expression status of c-MET.

BACKGROUND: This study aimed to investigate the prognostic value of volumetric parameters on 18F- fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in gastric-cancer patients, according to the expression status of c-MET (MET proto-oncogene, receptor tyrosine kinase), which was previously unclear. METHODS: The study included 61 patients with advanced gastric cancer. Data on the baseline 18F-FDG PET/CT, clinical-pathological information, progression-free survival (PFS), and overall survival (OS) were collected. The maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of gastric tumors in situ were measured on PET/CT. The expression status of c-MET was recorded based on immunohistochemical staining. Associations between the parameters on PET/CT and patients' survival outcomes were analyzed in relation to expression status of c-MET. RESULTS: Patients with positive c-MET expression had significantly shorter PFS (11.5 vs. 17.6 months, P = 0.039) and OS (17.0 vs. 24.3 months, P = 0.043), and had gastric tumors with a larger MTV (70.8 ± 53.11 vs. 41.1 ± 52.32, P = 0.034) and TLG (428.39 ± 442.95 vs. 205.7 ± 354.40, P = 0.039), compared with those with negative c-MET expression. However, SUVmax (9.6 ± 7.40 vs. 8.0 ± 4.91, P = 0.335) and SUVpeak (7.7 ± 5.99 vs. 6.62 ± 4.08, P = 0.438) were similar between these two patient groups. In patients with c-MET-positive tumors, MTV and TLG were independent factors in predicting patient OS after correction by distant metastasis (hazards ratio = 1.014 and 1.002, respectively; P = 0.024 and 0.027, respectively), while these associations were not significant in patients with c-MET-negative tumors. CONCLUSIONS: Patients with c-MET-positive gastric cancer had higher MTV and TLG values compared to those with c-MET-negative gastric cancer. In patients with c-MET-positive gastric cancer, volumetric parameters on 18F-FDG PET/CT have prognostic value for patient overall survival.

Epidemiology of ossification of the spinal ligaments and associated factors in the Chinese population: a cross-sectional study of 2000 consecutive individuals.

BACKGROUND: The epidemiology and cause of ossification of the spinal ligaments (OSL) remains obscure. To date, there is no study that comprehensively evaluates the prevalence, distribution, and concomitance of each type of OSL by CT among general Chinese population. We therefore aimed to comprehensively investigate epidemiological characteristics of OSL using whole spine CT in the Chinese population and examine the factors that correlate with the presence of OSL. METHODS: Ossification of the posterior longitudinal ligament (OPLL), ligamentum flavum (OLF), anterior longitudinal ligament (OALL), nuchal ligament (ONL), and diffuse idiopathic skeletal hyperostosis (DISH) were evaluated from the subjects who underwent PET/CT for the purpose of cancer screening in our hospital. Prevalence, distribution, and concomitance of OSL were reviewed. Logistic regression analysis was performed to identify the risk factors of OSL. RESULTS: A total of 2000 subjects (1335 men and 665 women) were included. The prevalence rate of cervical OPLL (C-OPLL) was 4.1%, thoracic OPLL (T-OPLL) 2.25%, lumbar OPLL (L-OPLL) 0.8%, thoracic OLF (T-OLF) 37.65%, lumbar OLF (L-OLF) 1.45%, ONL 31.5%, DISH 3.85%. The most commonly involved level was C5 for C-OPLL, T1 for T-OPLL, T10 for T-OLF, and T8/9 for OALL. 21% of subjects with C-OPLL had T-OPLL, 44% of C-OPLL had T-OLF, 38% of T-OPLL had C-OPLL, 53% of T-OPLL had T-OLF, 44% of L-OPLL had T-OPLL, and 56% of L-OPLL had T-OLF. The average age of OSL-positive subjects was significantly higher than that of OSL-negative subjects. The results of the multiple regression analysis revealed that males had a strong association with DISH (odds ratio, 3.15; 95% confidence interval, 1.27-7.78; P = 0.013). CONCLUSION: The prevalence of OSL in the Chinese was revealed. Tandem ossification is not uncommon in people with OSL. There is a high incidence of multiple-regional OPLL in the whole spine. Approximately half of the subjects with OPLL coexist with T-OLF. For patients with clinical symptoms induced by OPLL, thorough evaluation of whole spine using CT is recommended.