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.

Synthesis and biological evaluation of hydantoin derivatives as potent antiplasmodial agents.

Malaria, a devastating disease, has claimed numerous lives and caused considerable suffering, with young children and pregnant women being the most severely affected group. However, the emergence of multidrug-resistant strains of Plasmodium and the adverse side effects associated with existing antimalarial drugs underscore the urgent need for the development of novel, well-tolerated, and more efficient drugs to combat this global health threat. To address these challenges, six new hydantoins derivatives were synthesized and evaluated for their in vitro antiplasmodial activity. Notably, compound 2c exhibited excellent inhibitory activity against the tested Pf3D7 strain, with an IC50 value of 3.97 ± 0.01 nM, three-fold better than chloroquine. Following closely, compound 3b demonstrated an IC50 value of 27.52 ± 3.37 µM against the Pf3D7 strain in vitro. Additionally, all the hydantoins derivatives tested showed inactive against human MCR-5 cells, with an IC50 value exceeding 100 µM. In summary, the hydantoin derivative 2c emerges as a promising candidate for further exploration as an antiplasmodial compound.

Preoperative free access to water compared to fasting for planned cesarean under spinal anesthesia: a randomized controlled trial.

BACKGROUND: Contemporary guidance for preoperative feeding allows solids up to 6 hours and clear fluids up to 2 hours before anesthesia. Clinical trial evidence to support this approach for cesarean delivery is lacking. Many medical practitioners continue to follow conservative policies of no intake from midnight to the time of surgery, especially in pregnant women. OBJECTIVE: This study aimed to evaluate the pragmatic approach of permitting free access to water up to the call to dispatch to the operating theater vs fasting from midnight in preoperative oral intake restriction for planned cesarean delivery under spinal anesthesia on perioperative vomiting and maternal satisfaction. STUDY DESIGN: A randomized controlled trial was conducted in the obstetrical unit of the University of Malaya Medical Centre from October 2020 to May 2022. A total of 504 participants scheduled for planned cesarean delivery were randomized: 252 undergoing preoperative free access to water up to the call to dispatch to the operating theater (intervention group) and 252 undergoing fasting from midnight (fasting arm). The primary outcomes were perioperative vomiting and maternal satisfaction. Analyses were performed using t test, Mann-Whitney U test, and chi-square test, as appropriate. RESULTS: Of note, 9 of 252 patients (3.6%) in the intervention group and 24 of 252 patients (9.5%) in the control group had vomiting at up to 6 hours after completion of cesarean delivery (relative risk, 0.38; 95% confidence interval, 0.18-0.79; P=.007), and the maternal satisfaction scores (0-10 visual numerical rating scale) were 9 (interquartile range, 8-10) in the intervention group and 5 (interquartile range, 3-7) in the control group (P<.001). Assessed before dispatch to the operating theater, feeling of thirst was reported by 69 of 252 patients (27.4%) in the intervention group and 134 of 252 patients (53.2%) in the control group (relative risk, 0.52; 95% confidence interval, 0.41-0.65; P<.001), capillary glucose levels were 4.8±0.7 mmol/L in the intervention group and 4.9±0.8 mmol/L in the control group (P=.048), and preoperative intravenous fluid hydration was commenced in 49 of 252 patients (19.4%) in the intervention group and 76 of 252 patients (30.2%) in the control group (relative risk, 0.65; 95% confidence interval, 0.47-0.88; P=.005). In the operating theater, ketone was detected in the catheterized urine in 38 of 252 patients (15.1%) in the intervention group and 78 of 252 patients (31.0%) in the control group (relative risk, 0.49; 95% confidence interval, 0.25-0.59; P<.001), and the numbers of doses of vasopressors needed to correct hypotension were 2.3±1.7 in the intervention group and 2.7±2.2 in the control (P=.009). The recommendation rates for preoperative oral intake regimen to a friend were 95.2% (240/252) in the intervention group and 39.7% (100/252) in the control group (relative risk, 2.40; 95% confidence interval, 2.06-2.80; P<.001), in favor of free access to water. Other assessed maternal and neonatal outcomes were not different. CONCLUSION: Compared with fasting, free access to water in planned cesarean delivery reduced perioperative vomiting and was strongly favored by women. In addition, several pre- and intraoperative secondary outcomes were improved. However, postcesarean delivery recovery and neonatal outcomes were not different.

Preliminary insight on diarylpentanoids as potential antimalarials: In silico, in vitro pLDH and in vivo zebrafish toxicity assessment.

Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC50 values of 1.6, 2.5 and 3.1 µM, respectively. Meanwhile, MS87 (EC50 of 1.85 µM) shown the most active against the CQ-resistant Gombak A strain, and MS33A and MS33C the most effective P. knowlesi inhibitors (EC50 of 3.6 and 5.1 µM, respectively). The in vitro cytotoxicity of selected diarylpentanoids (MS33A, MS33C, MS34C and MS87) was tested on Vero mammalian cells to evaluate parasite selectivity (SI), showing moderate to low cytotoxicity (CC50 > 82 µM). In addition, MS87 exhibited a high SI and the lowest resistance index (RI), suggesting that MS87 may exert effective parasite inhibition with low resistance potential in the CQ-resistant P. falciparum strain. Furthermore, the in vivo toxicity of the molecules on early embryonic development, the cardiovascular system, heart rate, motor activity and apoptosis were assessed in a zebrafish animal model. The overall results indicate the preliminary potential of diarylpentanoids, which need further investigation for their development as new antimalarial agents.

Kinetic analysis of cardiac dynamic 18F-Florbetapir PET in healthy volunteers and amyloidosis patients: A pilot study.

Objectives: This study aimed to explore the potential of full dynamic PET kinetic analysis in assessing amyloid binding and perfusion in the cardiac region using 18F-Florbetapir PET, establishing a quantitative approach in the clinical assessment of cardiac amyloidosis disease. Materials & methods: The distribution volume ratios (DVRs) and the relative transport rate constant (R1), were estimated by a pseudo-simplified reference tissue model (pSRTM2) and pseudo-Logan plot (pLogan plot) with kidney reference for the region of interest-based and voxel-wise-based analyses. The parametric images generated using the pSRTM2 and linear regression with spatially constrained (LRSC) algorithm were then evaluated. Semi-quantitative analyses include standardized uptake value ratios at the early phase (SUVREP, 0.5-5 min) and late phase (SUVRLP, 50-60 min) were also calculated. Results: Ten participants [7 healthy controls (HC) and 3 cardiac amyloidosis (CA) subjects] underwent a 60-min dynamic 18F-Florbetapir PET scan. The DVRs estimated from pSRTM2 and Logan plot were significantly increased (HC vs CA; DVRpSRTM2: 0.95 ± 0.11 vs 2.77 ± 0.42, t'(2.13) = 7.39, P = 0.015; DVRLogan: 0.80 ± 0.12 vs 2.90 ± 0.55, t'(2.08) = 6.56, P = 0.020), and R1 were remarkably decreased in CA groups, as compared to HCs (HC vs CA; 1.08 ± 0.37 vs 0.56 ± 0.10, t'(7.63) = 3.38, P = 0.010). The SUVREP and SUVRLP were highly correlated to R1 (r = 0.97, P < 0.001) and DVR(r = 0.99, P < 0.001), respectively. The DVRs in the total myocardium region increased slightly as the size of FWHM increased and became stable at a Gaussian filter ≥6 mm. The secular equilibrium of SUVR was reached at around 50-min p.i. time. Conclusion: The DVR and R1 estimated from cardiac dynamic 18F-Florbetapir PET using pSRTM with kidney pseudo-reference tissue are suggested to quantify cardiac amyloid deposition and relative perfusion, respectively, in amyloidosis patients and healthy controls. We recommend a dual-phase scan: 0.5-5 min and 50-60 min p.i. as the appropriate time window for clinically assessing cardiac amyloidosis and perfusion measurements using 18F-Florbetapir PET.

The efficacy of short acquisition time using 18F-FDG total-body PET/CT for the identification of pediatric epileptic foci.

BACKGROUND: 18F-FDG positron emission tomography (PET) plays a crucial part in the evaluation for pediatric epileptic patients prior to therapy. Short-term scanning holds significant importance, especially for pediatrics epileptic individuals who exhibited involuntary movements. The aim was to evaluate the effects of short acquisition time on image quality and lesion detectability in pediatric epileptic patients using total-body (TB) PET/CT. A total of 25 pediatric patients who underwent TB PET/CT using uEXPLORER scanner with an 18F-FDG administered dose of 3.7 MBq/kg and an acquisition time of 600 s were retrospectively enrolled. Short acquisition times (60 s, 150 and 300 s) were simulated by truncating PET data in list mode to reduce count density. Subjective image quality was scored on a 5-point scale. Regions of interest analysis of suspected epileptogenic zones (EZs), corresponding locations contralateral to EZs, and healthy cerebellar cortex were used to compare the semi-quantitative uptake indices of short-time images and then were compared with 600 s images. The comparison of EZs detectability based on time-dependent PET images was performed. RESULTS: Our study demonstrated that a short acquisition time of 150 s is sufficient to maintain subjective image quality and lesion significance. Statistical analysis revealed no significant difference in subjective PET image quality between imaging at 300 s and 150 s (P > 0.05). The overall impression scores of image quality and lesion conspicuity in G60s were both greater than 3 (overall quality, 3.21 ± 0.46; lesion conspicuity, 4.08 ± 0.74). As acquisition time decreased, the changes of SUVmax and SD in the cerebellar cortex gradually increased (P < 0.01). There was no significant difference in asymmetry index (AI) difference between the groups and the AIs of EZs were > 15% in all groups. In 26 EZs of 25 patients, the lesion detection rate was still 100% when the time was reduced to 60 s. CONCLUSIONS: This study proposed that TB PET/CT acquisition time could be reduced to 60 s with acceptable lesion detectability. Furthermore, it was suggested that a 150 s acquisition time would be sufficient to achieve diagnostic performance and image quality for children with epilepsy.

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

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

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

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

The feasibility of quantitative assessment of dynamic 18F-fluorodeoxyglucose PET in Takayasu's arteritis: a pilot study.

PURPOSE: PET has been demonstrated to be sensitive for detecting active inflammation in Takayasu's arteritis (TAK) patients, but semi-quantitative-based assessment may be susceptible to various biological and technical factors. Absolute quantification via dynamic PET (dPET) may provide a more reliable and quantitative assessment of TAK-active arteries. The purpose of this study was to investigate the feasibility and efficacy of dPET in quantifying TAK-active arteries compared to static PET. MATERIALS AND METHODS: This prospective study enrolled 10 TAK-active patients (fulfilled the NIH criteria) and 5 control participants from March to October 2022. One-hour dPET scan (all TAK and control participants) and delayed static PET scan at 2-h (all TAK patients) were acquired. For 1-h static PET, summed images from 50 to 60 min of the dPET were extracted. PET parameters derived from 1- and 2-h static PET including SUV (SUV1H and SUV2H), target-to-background ratio (TBR) (TBR1H and TBR2H), net influx rate (Ki), and TBRKi extracted from dPET were obtained. The detectability of TAK-active arteries was compared among different scanning methods using the generalized estimating equation (GEE) with a logistic regression with repeated measures, and the GEE with gamma distribution and log link function was used to evaluate the different study groups or scanning methods. RESULTS: Based on the disease states, 5 cases of TAK were classified as untreated and relapsed, respectively. The SUVmax on 2-h PET was higher than that on 1-h PET in the untreated patients (P < 0.05). However, no significant differences were observed in the median SUVmax between 1-h PET and 2-h PET in the relapsed patients (P > 0.05). The TBRKi was significantly higher than both TBR1H and TBR2H (all P < 0.001). Moreover, the detectability of TAK-active arteries by dPET-derived Ki was significantly higher than 1-h and 2-h PET (all P < 0.001). Significant differences were observed in Kimax, SUVmax-1H, TBR1H, and TBRKi among untreated, relapsed, and control groups (all P < 0.05). CONCLUSIONS: Absolute quantitative assessment by dPET provides an improved sensitivity and detectability in both visualization and quantification of TAK-active arteries. This elucidates the clinical significance of dPET in the early detection of active inflammation and monitoring recurrence.

Improved [68Ga]Ga-PSMA-11 image qualities reconstructed by total variation regularized expectation maximization on total-body PET/CT.

Background: Total variation regularized expectation maximization (TVREM) reconstruction algorithm on the image quality of gallium (68GA) prostate-specific membrane antigen-11 ([68Ga]Ga-PSMA-11) total-body positron emission tomography/computed tomography (PET/CT). Methods: Images of a phantom with small hot sphere inserts and the total-body PET/CT scans of 51 prostate cancer patients undergoing [68Ga]Ga-PSMA-11 were reconstructed using TVREM with 5 different penalization factors between 0.09 and 0.45 and for 20-, 40-, 60-, 120-, and 300-second acquisition, respectively. As a comparison, the same data were also reconstructed using the ordered subset expectation maximization (OSEM) with 3 iterations, 20 subsets, and 300 second acquisition. The contrast recovery coefficients (CRC) and background variability (BV) of the phantom, the tumor-to-background ratios (TBR), the contrast recovery (CR) ratio, the image noise of the liver, and maximum standard uptake value (SUVmax) of the lesions were calculated to evaluate the image quality. The clinical performance of the images was evaluated by 2 radiologists with a 5-point scale (1-poor, 5-excellent). Results: The TVREM reconstructions groups fwith 120 second acquisition and the penalization of 0.27 to 0.45 showed the best performance in terms of CR, TBR, image noise, and the gain of SUVmax compared to that obtained in the OSEM 300 second group. Even the image noise of the TVREM 120 second group with a penalization factor of 0.27 and 0.36 was comparable to the OSEM 300 second group; the lesions' SUVmax increased by 28% whereas the image noise decreased by 5% and 14%, respectively. The TVREM 120 second group with a penalization factor of 0.36 (5.00±0.00) had the highest qualitative score that equaled OSEM and TVREM for the 300 second (P>0.05) group. Conclusions: Our study has shown the potential of the TVREM reconstruction algorithm with optimized penalization factors to achieve comparable [68Ga]Ga-PSMA-11 total-body PET/CT image quality with a shorter acquisition time, compared with the conventional OSEM reconstruction algorithm.

Improved accuracy of the biodistribution and internal radiation dosimetry of 13 N-ammonia using a total-body PET/CT scanner.

BACKGROUND: Conventional short-axis PET typically utilizes multi-bed multi-pass acquisition to produce quantitative whole-body dynamic images and cannot record all the uptake information simultaneously, resulting in errors when fitting the time-activity curves (TACs) and calculating radiation doses. PURPOSE: The aim of this study is to evaluate the 13 N-ammonia biodistribution and the internal radiation doses using a 194 cm long total-body PET/CT scanner (uEXPLORER), and make a comparison with the previous short-axis PET results. METHODS: Ten subjects (age 40-74 years) received 13 N-NH3 injection (418.1-670.81 MBq) and were under a dynamic scan for about 60 min with using a 3-dimensional whole-body protocol. ROIs were drawn visually on 11 major organs (brain, thyroid, gallbladder, heart wall, kidneys, liver, pancreas, spleen, lungs, bone marrow, and urinary bladder content) for each subject. TACs were generated using Pmod and the absorbed radiation doses were calculated using Olinda 2.2. To compare with the conventional PET/CT, five points were sampled on uEXPLORER's TACs to mimic the result of a short-axis PET/CT (15 cm axial FOV, consisted of 9 or 10 bed positions). Then the TACs were obtained using the multi-exponential fitting method, and the residence time and radiation dose were also calculated and compared with uEXPLORER. RESULTS: The highest absorbed organ doses were the pancreas, thyroid, spleen, heart wall, and kidneys for the male. For the female, the first five highest absorbed organ dose coefficients were the pancreas, heart wall, spleen, lungs, and kidneys. The lowest absorbed dose was found in red marrow both for male and female. The simulated short-axis PET can fit TACs well for the gradually-changed uptake organs but typically underestimated for the rapid-uptake organs during the first-10 min, resulting in errors in the calculated radiation dose. CONCLUSION: uEXPLORER PET/CT can measure 13 N-ammonia's TACs simultaneously in all organs of the whole body, which can provide more accurate biodistribution and radiation dose estimation compared with the conventional short-axis scanners.

First Total-Body Kinetic Modeling and Parametric Imaging of Dynamic 68Ga-FAPI-04 PET in Pancreatic and Gastric Cancer.

Fibroblast activation protein inhibitor (FAPI) is an ideal diagnostic and therapeutic target in malignant tumors. However, the knowledge of kinetic modeling and parametric imaging of 68Ga-FAPI is limited. Purpose: The purpose of this study was to explore the pharmacokinetics of 68Ga-FAPI-04 PET/CT in pancreatic cancer and gastric cancer and to conduct parametric imaging of dynamic total-body data compared with SUV imaging. Methods: Dynamic total-body 68Ga-FAPI-04 PET/CT was performed on 13 patients. The lesion time-activity curves were fitted by 3-compartment models and multigraphical models. The kinetics parameters derived from the 2-tissue reversible compartment model (2T4K) and multigraphical models were analyzed. Parametric [Formula: see text] imaging was generated using the 2T4K and Logan models, and their performances were evaluated compared with SUV images. Results: 2T4K had the lowest Akaike information criterion value, and its fitting curves matched excellently with the origin time-activity curves. Visual assessment revealed that the [Formula: see text](2T4K) images and [Formula: see text](Logan with spatial constraint [SC]) images both showed less image noise and higher lesion conspicuity compared with SUV images. Objective image quality assessment demonstrated that parametric [Formula: see text](2T4K) images and parametric [Formula: see text](Logan with SC) images had a 5.0-fold and 5.0-fold higher average signal-to-noise ratio and 3.6-fold and 4.1-fold higher average contrast-to-noise ratio compared with conventional SUV images, respectively. In addition, no significant differences in signal-to-noise ratio and contrast-to-noise of pathologic lesions were observed between parametric [Formula: see text](2T4K) images and parametric [Formula: see text](Logan with SC) images (all P > 0.05). Conclusions: The 2T4K model was the preferred compartment model. Total-body parametric imaging of 68Ga-FAPI-04 PET yielded superior quantification beyond SUV with enhanced lesion contrast, which may serve as a promising imaging method to make an early diagnosis, to better reflect tumor characterization, or to allow evaluation of treatment response. [Formula: see text](2T4K) images are comparable in image quality and consistent to [Formula: see text](Logan with SC) images in lesions conspicuity; however, [Formula: see text](Logan with SC) images presented an appealing alternative to [Formula: see text](2T4K) images because of their simplicity.

The Impact of Geographical Variation in Plasmodium knowlesi Apical Membrane Protein 1 (PkAMA-1) on Invasion Dynamics of P. knowlesi.

Plasmodium knowlesi has emerged as an important zoonotic parasite that causes persistent symptomatic malaria in humans. The signs and symptoms of malaria are attributed to the blood stages of the parasites, which start from the invasion of erythrocytes by the blood stage merozoites. The apical membrane protein 1 (AMA-1) plays an important role in the invasion. In this study, we constructed and expressed recombinant PkAMA-1 domain II (PkAMA-1-DII) representing the predominant haplotypes from Peninsular Malaysia and Malaysian Borneo and raised specific antibodies against the recombinant proteins in rabbits. Despite the minor amino acid sequence variation, antibodies raised against haplotypes from Peninsular Malaysia and Malaysian Borneo demonstrated different invasion inhibition (46.81% and 39.45%, respectively) to P. knowlesi A1-H.1, a reference strain derived from Peninsular Malaysia. Here, we demonstrated how a minor variation in a conserved parasite protein could cast a significant impact on parasite invasion biology, suggesting a complex host-switching of P. knowlesi from different locations. This may challenge the implementation of a standardized One Health approach against the transmission of knowlesi malaria.

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

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

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

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

Genetic polymorphism of the thrombospondin-related apical merozoite protein (TRAMP) of Plasmodium knowlesi in Malaysia.

Plasmodium knowlesi is a simian malaria parasite that causes significant zoonotic infections in Southeast Asia, particularly in Malaysia. The Plasmodium thrombospondin-related apical merozoite protein (TRAMP) plays an essential role in the invasion of the parasite into its host erythrocyte. The present study investigated the genetic polymorphism and natural selection of the full length PkTRAMP from P. knowlesi clinical isolates from Malaysia. Blood samples (n = 40) were collected from P. knowlesi malaria patients from Peninsular Malaysia and Malaysian Borneo. The PkTRAMP gene was amplified using PCR, followed by cloning into a plasmid vector and sequenced. Results showed that the nucleotide diversity of PkTRAMP was low (π: 0.009). Z-test results indicated negative (purifying) selection of PkTRAMP. The alignment of the deduced amino acid sequences of PkTRAMP of Peninsular Malaysia and Malaysian Borneo revealed 38 dimorphic sites. A total of 27 haplotypes were identified from the amino acid sequence alignment. Haplotype analysis revealed that there was no clustering of PkTRAMP from Peninsular Malaysia and Malaysian Borneo.

Tracer-specific reference tissues selection improves detection of 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir PET SUVR changes in Alzheimer's disease.

This study sought to identify a reference tissue-based quantification approach for improving the statistical power in detecting changes in brain glucose metabolism, amyloid, and tau deposition in Alzheimer's disease studies. A total of 794, 906, and 903 scans were included for 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir, respectively. Positron emission tomography (PET) and T1-weighted images of participants were collected from the Alzheimer's disease Neuroimaging Initiative database, followed by partial volume correction. The standardized uptake value ratios (SUVRs) calculated from the cerebellum gray matter, centrum semiovale, and pons were evaluated at both region of interest (ROI) and voxelwise levels. The statistical power of reference tissues in detecting longitudinal SUVR changes was assessed via paired t-test. In cross-sectional analysis, the impact of reference tissue-based SUVR differences between cognitively normal and cognitively impaired groups was evaluated by effect sizes Cohen's d and two sample t-test adjusted by age, sex, and education levels. The average ROI t values of pons were 86.62 and 38.40% higher than that of centrum semiovale and cerebellum gray matter in detecting glucose metabolism decreases, while the centrum semiovale reference tissue-based SUVR provided higher t values for the detection of amyloid and tau deposition increases. The three reference tissues generated comparable d images for 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir and comparable t maps for 18 F-florbetapir and 18 F-flortaucipir, but pons-based t map showed superior performance in 18 F-FDG. In conclusion, the tracer-specific reference tissue improved the detection of 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir PET SUVR changes, which helps the early diagnosis, monitoring of disease progression, and therapeutic response in Alzheimer's disease.

Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative Virulence-Associated Differentially Abundant Membrane Proteins.

Entamoeba histolytica is a protozoan parasite that causes amebiasis and poses a significant health risk for populations in endemic areas. The molecular mechanisms involved in the pathogenesis and regulation of the parasite are not well characterized. We aimed to identify and quantify the differentially abundant membrane proteins by comparing the membrane proteins of virulent and avirulent variants of E. histolytica HM-1:IMSS, and to investigate the potential associations among the differentially abundant membrane proteins. We performed quantitative proteomics analysis using isobaric tags for relative and absolute quantitation labeling, in combination with two mass spectrometry instruments, that is, nano-liquid chromatography (nanoLC)-matrix-assisted laser desorption/ionization-mass spectrometry/mass spectrometry and nanoLC-electrospray ionization tandem mass spectrometry. Overall, 37 membrane proteins were found to be differentially abundant, whereby 19 and 18 membrane proteins of the virulent variant of E. histolytica increased and decreased in abundance, respectively. Proteins that were differentially abundant include Rho family GTPase, calreticulin, a 70-kDa heat shock protein, and hypothetical proteins. Analysis by Protein ANalysis THrough Evolutionary Relationships database revealed that the differentially abundant membrane proteins were mainly involved in catalytic activities (29.7%) and metabolic processes (32.4%). Differentially abundant membrane proteins that were found to be involved mainly in the catalytic activities and the metabolic processes were highlighted together with their putative roles in relation to the virulence. Further investigations should be performed to elucidate the roles of these proteins in E. histolytica pathogenesis.

Rodent Species Distribution and Hantavirus Seroprevalence in Residential and Forested areas of Sarawak, Malaysia.

Rodents belong to the order Rodentia, which consists of three families in Borneo (i.e., Muridae, Sciuridae and Hystricidae). These include rats, mice, squirrels, and porcupines. They are widespread throughout the world and considered pests that harm humans and livestock. Some rodent species are natural reservoirs of hantaviruses (Family: Bunyaviridae) that can cause zoonotic diseases in humans. Although hantavirus seropositive human sera were reported in Peninsular Malaysia in the early 1980s, information on their infection in rodent species in Malaysia is still lacking. The rodent populations in residential and forested areas in Sarawak were sampled. A total of 108 individuals from 15 species of rodents were collected in residential (n = 44) and forested ( n = 64) areas. The species diversity of rodents in forested areas was significantly higher (H = 2.2342) compared to rodents in residential areas (H = 0.64715) (p < 0.001 of Zar-t test based on the Shannon index). Rattus rattus and Sundamys muelleri were present at high frequencies in both localities. An enzyme-linked immunosorbent assay (ELISA) showed that hantavirus-targeting antibodies were absent from 53 tested serum samples. This is the first report of hantavirus seroprevalence surveillance in rodent populations in Sarawak, East Malaysia. The results suggested that hantavirus was not circulating in the studied rodent populations in Sarawak, or it was otherwise at a low prevalence that is below the detection threshold. It is important to remain vigilant because of the zoonotic potential of this virus and its severe disease outcome. Further studies, such as molecular detection of viral genetic materials, are needed to fully assess the risk of hantavirus infection in rodents and humans in this region of Malaysia.