Parametric net influx rate imaging of 68Ga-DOTATATE in patients with neuroendocrine tumors: assessment of lesion detectability.

OBJECTIVES: There has been developed a clinical dynamic total-body 68Ga-DOTATATE PET/CT imaging protocol that allows quantitative imaging of net influx rate (Ki). Using qualitative and quantitative analyses of clinical studies, this retrospective study aims to assess whether parametric Ki images improve lesion detectability. METHODS: Using a 194-cm axial field-of-view PET/CT scanner, 52 patients with neuroendocrine tumors underwent a 60-min dynamic total-body 68Ga-DOTATATE scan. Parametric Ki images and static standardized uptake value (SUV) images were generated. In addition to visual inspection of both sets of images, a quantitative analysis of 249 individual lesions was conducted using the target-to-background (TBR) metric. RESULTS: There were 52 patients who underwent dynamic total-body 68Ga-DOTATATE PET/CT scans. A total of 249 lesions were evaluated, of which 66 lesions were biopsy-proven and 183 lesions were unproven. Ki images produced two fewer false positives than the SUV images. Overall, our results from 66 proven NET lesions suggested similar sensitivity (98.5%) but improved accuracy (from 95.6 to 97.1%) and potentially enhanced specificity with Ki over SUV imaging. Besides, there was no difference in the number of pathological lesions identified visually in both images. However, Ki TBR was significantly higher than SUV TBR quantitatively (P < 0.001). CONCLUSIONS: Patlak Ki imaging provides nuclear physicians with a PET image with higher tumor contrast which may enhance confidence in diagnosis with possibly reduced false positive results, albeit an equivalent detectability, compared to static SUV image.

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.

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.

One-tenth-activity total-body positron emission tomography versus full-activity imaging in patients with a complex of hepatic malignant tumors: a retrospective study.

Background: The value of ultra-low-activity 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging in patients with hepatic malignancies remains unclear. Methods: A cross-sectional study was conducted from April 2019 to May 2021 in Zhongshan Hospital, Fudan University. A total of 49 patients with hepatic malignancies, including hepatocellular carcinoma (HCC) (n=13) or intrahepatic cholangiocarcinoma (ICC) (n=36), underwent 60-min dynamic PET imaging, with 15 undergoing full-activity 18F-FDG and 34 undergoing ultra-low-activity 18F-FDG. The kinetic metrics (K1-k3, and Ki) of tumors were calculated and compared between the activity groups. Another 54 patients (27 each group) with hepatic malignancies, including HCC (n=9), ICC (n=34), and metastases (n=11), underwent static imaging. Image qualities were compared between the groups in terms of 5-point Likert scores (with a score ≥3 fulfilling the clinical requirement), the mean standardized uptake value (SUVmean), the standard deviation of standardized uptake value (SUVSD), and the signal-to-noise ratio (SNR) of the liver; the SUVmean of blood pool and muscle; and the tumor-to-liver ratio (TLR), tumor-to-blood ratio (TBR), and tumor-to-muscle ratio (TMR) of lesions. Intergroup comparisons were performed using Chi-squared test for categorical variables and the Student's t-test or the Mann-Whitney test for continuous variables depending on the normality of variables. Results: There was a nonsignificant difference in the kinetic metrics (K1-k3 and Ki) of tumors between the activity groups. In static imaging, 1-min full-activity (F1) and 8-min ultra-low-activity (L8) images obtained image-quality scores >3 and were thus selected for intergroup comparisons. Nonsignificant differences in SUVmean of liver, blood pool, and muscle were identified between F1 and L8 images (P=0.641, P=0.542, and P=0.073, respectively) although the liver SNR was slightly higher in F1 (13.10 vs. 11.31; P=0.003). Lesion detectability was 98.5% and 100% for F1 and L8 images, respectively, but there were no significant differences in TLR, TBR, or TMR between the groups. Conclusions: The results of this single-center study indicate that the performance of ultra-low-activity PET imaging is comparable to that of full-activity imaging in patients with hepatic malignancies.

Dynamic 68Ga-DOTA0-Tyr3-octreotate positron emission tomography-computed tomography for the evaluation of pancreatic neuroendocrine tumors: a pilot study.

Background: 68Ga-DOTA0-Tyr3-octreotate (68Ga-DOTATATE) is a radiolabeled somatostatin analog used for the diagnosis of pancreatic neuroendocrine tumors (pNETs), and standardized uptake value (SUV) measurements for therapeutic monitoring is recommended. However, changes in net influx rate (Ki) may better reflect treatment effects than may those of the SUV. The aim of this study was to investigate the value of dynamic 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT) in the evaluation of pNETs. Methods: Dynamic PET-CT scans over 60 min were acquired for 7 patients with localized pancreatic mass before surgery. Maximal and mean SUV (SUVmax and SUVmean) were measured in tumors and normal pancreatic body as reference tissue (RT). Time-activity curves (TACs) were extracted from tumors and RT. A 2-tissue compartment model was used to calculate the rate constants K1, k2, and k3 (min-1); Ki (mL/g/min); and K1:k2 ratio. The following statistical tests were used to evaluate the results: the Shapiro-Wilk, Student t test, Mann-Whitney, Spearman, and Pearson rank correlation tests. Results: Among 6 patients, 8 primary tumors were histopathologically proven to be pNETs. Moreover, 6 lesions with high uptake of 68Ga-DOTATATE showed an ascending TAC pattern, while 2 lesions with no or low uptake showed a descending TAC pattern. The mean SUVmax and SUVmean of pNETs were 46.4±40.2 (range, 3.9-109.9) and 21.9±16.0 (range, 0.5-42.8), respectively, which were significantly higher than the SUVmax of 4.2±0.6 (range, 3.1-4.9) and the SUVmean of 2.7±1.0 (range, 1.4-3.6) for the RT (P=0.021 and P=0.036), respectively. The Ki of pNETs was statistically higher than that of the RT [pNET: 0.366±0.372 (range, 0.019-0.992); RT: 0.060±0.017 (range, 0.04-0.08); P=0.036]. The mean K1:k2 ratio in pNETs was 12-fold higher than that of RT (6.06 vs. 0.50). In pNETs, there was a positive correlation between SUVmax and Ki (r=0.952; P<0.001) and between SUVmean and Ki (r=0.905; P=0.002). Another patient was diagnosed with intrapancreatic accessory spleen. Conclusions: The uptake of 68Ga-DOTATATE by pNETs can be explained by its high Ki value and K1:k2 ratio. Dynamic 68Ga-DOTATATE PET-CT can serve as a potential tool for evaluating pNETs and support the further assessment of a larger cohort of patients.

Comparative efficacy of endogenous stem cells recruiting hydrogels and stem cell-loaded hydrogels in knee cartilage regeneration: a meta-analysis.

Background Cartilage defects remain a challenge in diseases such as osteoarthritis (OA) and fractures. Scientists have explored the use of hydrogels in conjunction with stem cell technology as a tissue engineering method to treat cartilage defects in joints. In recent years, research into hydrogels containing stem cell technology for cartilage repair has mainly focused on two categories: stem cell-loaded hydrogels and endogenous stem cell recruiting hydrogels. The latter, utilizing cell-free products, represents a novel concept with several advantages, including easier dose standardization, wider sources, and simpler storage. This meta-analysis aims to assess and compare the therapeutic effects of endogenous stem cell recruiting hydrogels and stem cell-loaded hydrogels in promoting articular cartilage regeneration in animal models, with the goal of exploring endogenous stem cell recruiting hydrogels as a promising replacement therapy for knee cartilage regeneration in preclinical animal studies. Methods We systematically searched PubMed, Web of Science, Cochrane Library, and Embase until January 2023 using key words related to stem cells, cartilage regeneration and hydrogel. A random-effects meta-analysis was performed to evaluate the therapeutic effect on newborn cartilage formation. Stratified analyses were also carried out by independently classifying trials according to similar characteristics. The level of evidence was determined using the GRADE method. Results Twenty-eight studies satisfied the inclusion criteria. Comprehensive analyses revealed that the use of endogenous stem cell recruiting hydrogels significantly promoted the formation of new cartilage in the knee joint, as evidenced by the histological score (3.77, 95% CI 2.40, 5.15; p < 0.0001) and the International Cartilage Repair Society (ICRS) macroscopic score (3.00, 95% CI 1.83, 4.18; p = 0.04), compared with the control group. The stem cell-loaded hydrogels also increased cartilage regeneration in the knee with the histological score (3.13, 95% CI 2.22, 4.04; p = 0.02) and the ICRS macroscopic score (2.49, 95% CI 1.16, 3.82; p =0.03) in comparison to the control. Significant heterogeneity between studies was observed, and further stratified and sensitivity analyses identified the transplant site and modelling method as the sources of heterogeneity. Conclusion The current study indicates that both endogenous stem cell recruiting hydrogels and stem cell loaded hydrogels can effectively promote knee joint cartilage regeneration in animal trials.

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.

Comparison of 18F-FDG PET/MR and PET/CT for pretreatment TNM staging of hilar cholangiocarcinoma.

PURPOSE: 18F-FDG PET/MR has been applied to the diagnosis and preoperative staging in various tumor types; however, reports using PET/MR in hilar cholangiocarcinoma (HCCA) are rare. We investigated the value of PET/MR for preoperative staging and compared it with PET/CT in HCCA. METHODS: Fifty-eight patients with HCCA confirmed by pathology were retrospectively analyzed. 18F-FDG PET/CT imaging was performed first, followed with whole-body PET/MR imaging. SUVmax of tumor and normal liver tissue were measured. Paired T test was used to compare SUVmax of tumor and normal liver tissue of PET/CT and PET/MR. In addition, McNemar test was used to compare the accuracy of TNM staging and Bismuth-Corlette typing between PET/CT and PET/MR. RESULTS: There was no significant difference in SUVmax between PET/CT and PET/MR in primary tumor lesions (6.6 ± 5.5 vs. 6.8 ± 6.2, P = 0.439). SUVmax of PET/CT and PET/MR in normal liver parenchyma was significantly different (3.0 ± 0.5 vs. 2.1 ± 0.5, P < 0.001). The accuracy of PET/MR in diagnosing T staging and N staging was significantly higher than those of PET/CT (72.4% vs. 58.6%, P = 0.022 and 84.5% vs. 67.2%, P = 0.002). There was no significant difference between PET/CT and PET/MR in M staging (94.8% vs. 98.3%, P = 0.5). The classification accuracy of PET/MR in Bismuth-Corlette was significantly higher than that of PET/CT (89.7% vs. 79.3%), P = 0.031. CONCLUSIONS: The diagnostic accuracy of 18F-FDG PET/MR was superior to that of PET/CT in preoperative T staging, N staging, and Bismuth-Corlette classification of HCCA. In M staging, the diagnostic accuracy of PET/MR was similar to that of PET/CT.

Neuroendocrine Neoplasms: Total-body PET/Computed Tomography.

Total-body PET/computed tomography (CT) (uExplorer) static and dynamic scan using low-dose (48.1 to 73.6 MBq) gallium-68 (68Ga) DOTATATE combined with low-dose (1.55 MBq/kg) or ultra-low-dose (0.37 MBq/kg) 18F-fluorodeoxyglucose (18F-FDG) were used as a routine in patients with neuroendocrine neoplasms (NENs). 68Ga DOTATATE and 18F-FDG PET/CT static imaging play complementary roles in diagnosis, staging, and therapy-response evaluation in a patient with NENs. Kinetic parameters and time activity curve derived from the dynamic scan is helpful for understanding tumors biological characteristics and differential diagnosis of NENs.

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.

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.

Dynamic Total-Body PET/CT Imaging Reveals Kinetic Distribution of 68Ga-DOTATATE in Normal Organs.

Objective: To investigate the biodistribution and kinetic constants of 68Ga-DOTATATE in normal organs through dynamic total-body positron emission tomography/computed tomography (PET/CT). Methods: Seven patients who experienced endoscopic resection of gastric neuroendocrine tumor were enrolled. Dynamic total-body PET/CT scans over 60 min were performed. Time-activity curves were obtained by drawing regions of interest in normal organs. Rate constants, including K 1, k 2, k 3, and vB, were computed using a two-tissue compartment model. Factor analysis was used to compare the rate constants among subjects and regions. Hierarchical cluster analysis was performed to identify organs with similar kinetic characteristics. Results: The highest uptake of 68Ga-DOTATATE was observed in the spleen followed by kidneys, adrenals, liver, pituitary gland, pancreas head, prostate, pancreas body, and thyroid, parotid, and submandibular glands. Low background level of 68Ga-DOTATATE uptake was observed in the nasal mucosa, bone, blood pool, and cerebrum. In addition, the uptake in the pancreas head was noted to be higher than the pancreas body (P < 0.001) on the basis of each time point of dynamic PET. There were differences of rate constants among different organs. The mean K 1 ranged from 0.0507 min-1 in the left nasal mucosa to 1.21 min-1 in the left kidney, and mean k 2 ranged from 0.0174 min-1 in the spleen to 4.4487 min-1 in the left cerebrum. The mean k 3 ranged from 0.0563 min-1 in the right cerebrum to 4.6309 min-1 in the left adrenal, and mean vB ranged from 0.0001 in the left cerebrum to 0.2489 in the right adrenal. However, none of the rate constants was significantly different among subjects or among different sites within a single organ. Three groups of organs with similar kinetic characteristics were identified: (1) cerebrum; (2) pituitary gland, liver, adrenal, and prostate; and (3) nasal mucosa, parotid and submandibular glands, thyroid, spleen, pancreas, kidney, and bone. Conclusion: Uptake and clearance of 68Ga-DOTATATE, in terms of kinetic constants, were different in different organs. The kinetic parameters of 68Ga-DOTATATE in different organs provide a reference for future dynamic PET imaging.

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.

A personal acquisition time regimen of 68Ga-DOTATATE total-body PET/CT in patients with neuroendocrine tumor (NET): a feasibility study.

BACKGROUND: The injection activity of tracer, acquisition time, patient-specific photon attenuation, and large body mass, can influence on image quality. Fixed acquisition time and body mass related injection activity in clinical practice results in a large difference in image quality. Thus, this study proposes a patient-specific acquisition time regimen of 68 Ga-DOTATATE total-body positron emission tomography-computed tomography (PET/CT) to counteract the influence of body mass (BM, kg) on image quality, and acquire an acceptable and constant image of patients with neuroendocrine tumors (NETs). METHODS: The development cohort consisting of 19 consecutive patients with full activity (88.7-204.9 MBq, 2.0 ± 0.1 MBq/kg) was to establish the acquisition time regimen. The liver SNR (signal-to-noise ratio, SNRL) was normalized (SNRnorm) by the product of injected activity (MBq) and acquisition time (min). Fitting of SNRnorm against body mass (BM, kg) in linear correlation was performed. Subjective assessment of image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL, and an optimized acquisition regimen based on BM was proposed, and validated its feasibility through the validation cohort of 57 consecutive NET patients with half activity (66.9 ± 11.3 MBq, 1.0 ± 0.1 MBq/kg) and a fixed acquisition time regimen. RESULTS: The linear correlation (R2 = 0.63) between SNRnorm and BM (kg) was SNRnorm = -0.01*BM + 1.50. The threshold SNRL of acceptable image quality was 11.2. The patient-specific variable acquisition time regimen was determined as: t (min) = 125.4/(injective activity)*(-0.01*BM + 1.50)2. Based on that proposed regimen, the average acquisition time for acceptable image quality in the validation cohort was 2.99 ± 0.91 min, ranging from 2.18 to 6.35 min, which was reduced by 36.50% ~ 78.20% compared with the fixed acquisition time of 10 min. Subjective evaluation showed that acceptable image quality could be obtained at 3.00 min in the validation group, with an average subjective score of 3.44 ± 0.53 (kappa = 0.97, 95% CI: 0.96 ~ 0.98). Bland-Altman analysis revealed good agreement between the proposed regimen and the fixed acquisition time cohort. CONCLUSION: A patient-specific acquisition time regimen was proposed in NET patients in development cohort and validated its feasibility in patients with NETs in validation cohort by 68 Ga-DOTATATE total-body PET/CT imaging. Based on the proposed regimen, the homogenous image quality with optimal acquisition time was available independent of body mass.

Longitudinal Positron Emission Tomography Imaging with P2X7 Receptor-Specific Radioligand 18F-FTTM in a Kainic Acid Rat Model of Temporal Lobe Epilepsy.

P2X7 receptors (P2X7R), as a brain inflammation biomarker, play important roles in the epileptogenic progress. Mounting evidence supports their activation in the brain during epilepsy, and inhibition of the P2X7 receptor reduces the seizure frequency and severity. In this study, we investigate P2X7R-targeted (18F-FTTM) position emission tomography (PET) imaging in a rat model of temporal lobe epilepsy to obtain further insights into the role of P2X7R during epileptogenesis. 18F-FTTM (5-10% radiochemical yield, over 99% radiochemical purity, and a specific activity of 270-300 MBq/nmol, n = 6, EOS) was first synthesized. Then, the rat models induced by intrahippocampal injection of saline (1.2 µL, n = 15) or kainic acid (1.2 µL, 0.5 µg/µL, n = 35) were examined using 18F-FTTM Micro-PET/CT longitudinal imaging, respectively. The imaging results showed that increases in the 18F-FTTM uptake was evident after status epilepticus (SE) in the epileptogenesis-associated brain regions, such as the hippocampus, amygdala, or temporal cortex, and this peaked during the latent period. The histopathological analysis revealed that the P2X7R PET uptake reached a peak at 7 days after SE and was mostly related to microglial activation. Thus, P2X7R-targeted PET imaging agent 18F-FTTM may act as a useful tool for identifying brain inflammation during epilepsy. P2X7R PET is a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and to monitor treatment response, and it warrants further clinical studies.

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.

The feasibility of ultralow-activity 18F-FDG dynamic PET imaging in lung adenocarcinoma patients through total-body PET/CT scanner.

OBJECTIVE: To explore the feasibility of ultralow-activity 18F-FDG total-body dynamic PET imaging for clinical practice in patients with lung adenocarcinoma. METHODS: Eight of 18 patients were randomly injected with 18F-FDG with full activity (3.7 MBq/kg) for total-body dynamic PET imaging, while 10 received one-tenth activity (0.37 MBq/kg). The generated time-to-activity curves (TACs) according to the regions of interest (ROIs) were processed by PMOD through standard FDG two-tissue compartment model fitting. The kinetic constant rates (K1, K2, K3, and Ki), radiation dose, prompt counts, and data storage size were analysed between the full- and ultralow-activity groups. The SUVmax-Tumour/SUVmax-Liver and SUVmax-Tumour/SUVmax-Muscle on static PET images were also assessed. RESULTS: Each of the fitted models has a satisfactory goodness-of-fit with R2 greater than 0.9 except 3 (3/234) in ultralow-activity group, where one in pancreas (R2 = 0.851), another one in muscle (R2 = 0.868), and the third one in bone marrow (R2 = 0.895). All the fitted models in the full-activity group had a better goodness-of-fit than those in the ultralow-activity group. However, no significant differences were found in any of the kinetic metrics or image quality between the two groups except in the reduction of radiation dose and data storage size. CONCLUSIONS: The 10 × reduction of injected 18F-FDG could achieve comparable kinetic metrics and T/N ratios by total-body dynamic PET imaging in lung adenocarcinoma patients. Ultralow-activity total-body PET imaging is feasible for clinical practice in oncological patients without obesity, especially in dynamic PET scanning.

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.