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.

A single-center, multi-factor, retrospective study to improve the diagnostic accuracy of primary prostate cancer using [68Ga]Ga-PSMA-11 total-body PET/CT imaging.

PURPOSE: To improve the diagnostic accuracy of initial detection in patients with suspected primary prostate cancer (PCa). METHODS: Eighty-four patients who underwent Gallium-68-labeled prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) total-body positron emission tomography/computed tomography (PET/CT) imaging before treatment in our department were enrolled. The maximum standard uptake value (SUVmax) of the prostate (SUVmax-PSMA), liver (SUVmax-PSMA-L), and mediastinal blood pool (SUVmax-PSMA-M) was measured using [68Ga]Ga-PSMA-11 total-body PET/CT imaging. The [68Ga]Ga-PSMA-11 derived metabolic tumor volume (MTV), the total lesion (TLP), and the cross-sectional areas of focal concentration in the prostate (CAP) were also determined. Besides, the prostate-specific antigen (PSA) levels and the above imaging characteristics were analyzed using receiver operating characteristic curves to identify the cutoff value to improve the diagnostic accuracy of suspected PCa. Finally, a multivariate regression analysis was conducted to discover the independent predictor to improve the diagnostic accuracy on [68Ga]Ga-PSMA-11 total-body imaging. RESULTS: There was no significant difference between the PCa and Non-PCa groups in age, height, weight, injected dose, except for the PSA levels, the SUVmax-PSMA, TLP, MTV, and CAP. Besides, the SUVmax-PSMA-T/L and SUVmax-PSMA-T/M derived from SUVmax-PSMA were both significantly different. In addition, the areas under the curve of PSA levels, SUVmax-PSMA, SUVmax-PSMA-T/L, SUVmax-PSMA-T/M, TLP, MTV, and CAP to predict PCa on [68Ga]Ga-PSMA-11 imaging were 0.620 (95% confidence interval (CI) 0.485-0.755), 0.864 (95% CI 0.757-0.972), 0.819 (95% CI 0.704-0.935), 0.876 (95% CI 0.771-0.980), 0.845 (95% CI 0.741-0.949), 0.820 (95% CI 0.702-0.938), 0.627 (95% CI 0.499-0.754), respectively. However, a multivariate regression analysis showed that SUVmax-PSMA was an independent predictor, with a cutoff value of 11.5 and an odds ratio of 1.221. CONCLUSION: The SUVmax-PSMA with a cutoff value of 11.5 was an independent predictor to improve the diagnostic accuracy of PCa on [68Ga]Ga-PSMA-11 total-body imaging.

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.

Exploration the feasibility and additional value of [18F]FDG/[68Ga]Ga-FAPI-04 dual-low-activity-tracer one-stop total-body PET imaging at 34 min post-injection of [68Ga]Ga-FAPI-04.

OBJECTIVES: To validate the feasibility of one-stop 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [68Ga]Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) dual-low-activity-tracer positron emission tomography/computed tomography (PET/CT) at 34 min post-injection of [68Ga]Ga-FAPI-04 and explore its additional value. METHODS: Thirty pairs of patients with suspected malignancies who underwent dual-tracer imaging were enrolled in this retrospective study. The images were reconstructed at 34-39 and 50-60 min after additional injection of [68Ga]Ga-FAPI-04 (in one-stop FDG-FAPI PET/CT, named PETFDG, PETD34-39, and PETD50-60; in the 2-day protocol, named PETFDG', PETF34-39, and PETF50-60, respectively). Tumour-to-normal ratios (TNR) of lesions in PETFDG, PETD34-39, and PETD50-60 and TNR of lesions in PETF34-39 and PETF50-60 were evaluated separately. To evaluate the potential added value of one-stop FDG-FAPI PET/CT over the 2-day protocol, TNRs of PETFDG, PETD34-39, and PETD50-60 were compared with PETF34-39. The lesion detectability of the two imaging protocols was evaluated by chi-square test. RESULTS: Comparing FAPI-weighted PET (PETD34-39 and PETD50-60) and single-tracer imaging (PETFDG) in one-stop FDG-FAPI PET/CT, TNRs of FAPI-weighted PET were higher than those of PETFDG. PETD34-39 and PETD50-60 showed similar performance in lesion detectability and TNRs (all P > 0.05). In the 2-day protocol, there are no statistically significant differences in TNRs of all lesions at PETF34-39 and PETF50-60. Comparing one-stop FDG-FAPI PET/CT with the 2-day protocol, TNRs of PETF34-39 were significantly higher than those of PETFDG but lower than those of PETD34-39 and PETD50-60. Lesion detectability in the one-stop FDG-FAPI PET/CT was higher than that in the 2-day protocol. The average radiation dose in one-stop FDG-FAPI PET/CT was significantly lower than that in the 2-day protocol (P<0.001). CONCLUSION: One-stop FDG-FAPI PET/CT at 34 min could provide sufficient information to meet clinical diagnosis and showed better lesion detectability than that in the 2-day protocol.

Preclinical Evaluation of 99mTc-MAG3-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with 99mTc-MAG3-5-F(ab')2.

Triggering receptor expressed on myeloid cells-2 (TREM2), which is expressed on the surface of tumor-associated macrophages (TAMs), has been found to play a major role in the diagnosis and treatment of tumors. TREM2 expression is significantly upregulated in tumor tissues, and therefore, targeting TREM2 for tumor imaging may be of value. Previously, we performed TREM2 targeting imaging by using 68Ga-NOTA-COG1410 or a 124I-labeled monoclonal antibody (mAb) and F(ab')2 in mouse models of colon and gastric tumors. However, some of the shortcomings of these probes (i.e., the high uptake of 68Ga-NOTA-COG1410 in the liver, the difficulty of obtaining iodine-124, and the long half-life of iodine-124) have hindered their clinical use. Herein, we sought to synthesize novel molecular probes targeting TREM2 that are more conducive to clinical translation, eliminating the interference of isotope availability and in vivo probe biodistribution issues. Therefore, we established A549 cell lines with negative human TREM2 (hTREM2) expression (GFP tag; hTREM2- A549) or upregulated hTREM2 expression (GFP tag; hTREM2+ A549) using lentiviral transfection and confirmed these with Western blotting and immunocytochemistry. We then prepared a mouse anti-human TREM2 (5-mAb) by immunizing with the hTREM2 antigen. The antibody fragments 5-F(ab')2 and 5-Fab were prepared from 5-mAb, and 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab were then synthesized with excellent stability and specificity. 99mTc-MAG3-5-F(ab')2 had a slightly higher in vitro affinity than 99mTc-MAG3-5-Fab (Kd = 3.32 ± 0.05 nmol versus 4.62 ± 0.85 nmol). 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab both showed excellent specificity: after adding a 100-fold precursor, the two probes binding to the cells were almost blocked. In vivo pharmacokinetics showed that the distribution and elimination half-lives of 99mTc-MAG3-5-Fab (T1/2α = 1.25 ± 0.30 min and T1/2ß = 21.98 ± 2.80 min, respectively) were significantly reduced compared to those of 99mTc-MAG3-5-F(ab')2 (T1/2α = 2.64 ± 0.37 min and T1/2ß = 86.55 ± 26.86 min, respectively). In micro single-photon emission computed tomography/computed tomography (micro-SPECT/CT) imaging, the tumor was clearly displayed at 1 h after 99mTc-MAG3-5-Fab injection, while the blood background was extremely low at 3 h, and the probe was mainly excreted through the kidneys and biliary tract. 99mTc-MAG3-5-F(ab')2 uptake was also detected at the tumor site, although the blood background was consistently high. The biodistribution results were consistent with the micro-SPECT/CT imaging results. 99mTc-MAG3-5-Fab could clearly display hTREM2+ A549 tumors in a short time (1 h) with low uptake in nontumor organs and tissues and thus has clinical application prospects.

Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4.

Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [68Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [177Lu]Lu-pentixather, the therapeutic companion of [68Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-d-Tyr-n-me-d-Orn-l-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [124I]I-1 ([124I]I-CPCR4), [99mTc]Tc-2 ([99mTc]Tc-HYNIC-CPCR4), [124I]I-3 ([124I]I-pentixafor), [18F]AlF-4 ([18F]AlF-NETA-CPCR4), [99mTc]Tc-5 ([99mTc]Tc-MAG3-CPCR4) and [124I]I-6 ([124I]I-pentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [124I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [68Ga]Ga-pentixafor group with the [124I]I-6 group, we found that the [124I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide (131I) labeling, and the tumor-bearing animal models were treated with [131I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [124I]I-6 and [131I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.

Evaluation of a Positron Emission Tomography Tracer Targeting Colony-Stimulating Factor 1 Receptor for Detecting Pulmonary Inflammation.

Colony-stimulating factor 1 receptor (CSF1R) is a type III receptor tyrosine kinase that is crucial for immune cell activation, survival, proliferation, and differentiation. Its expression significantly increases in macrophages during inflammation, playing a crucial role in regulating inflammation resolution and termination. Consequently, CSF1R has emerged as a critical target for both therapeutic intervention and imaging of inflammatory diseases. Herein, we have developed a radiotracer, 1-[4-((7-(dimethylamino)quinazolin-4-yl)oxy)phenyl]-3-(4-[18F]fluorophenyl)urea ([18F]17), for in vivo positron emission tomography (PET) imaging of CSF1R. Compound 17 exhibits a comparable inhibitory potency against CSF1R as the well-known CSF1R inhibitor PLX647. The radiosynthesis of [18F]17 was successfully performed by radiofluorination of aryltrimethyltin precursor with a yield of approximately 12% at the end of synthesis, maintaining a purity exceeding 98%. In vivo stability and biodistribution studies demonstrate that [18F]17 remains >90% intact at 30 min postinjection, with no defluorination observed even at 60 min postinjection. The PET/CT imaging study in lipopolysaccharide-induced pulmonary inflammation mice indicates that [18F]17 offers a more sensitive characterization of pulmonary inflammation compared to traditional [18F]FDG. Notably, [18F]17 shows a higher discrepancy in uptake ratio between mice with pulmonary inflammation and the sham group. Furthermore, the variations in [18F]17 uptake ratio observed on day 7 and day 14 correspond to lung density changes observed in CT imaging. Moreover, the expression levels of CSF1R on day 7 and day 14 follow a trend similar to the uptake pattern of [18F]17, indicating its potential for accurately characterizing CSF1R expression levels and effectively monitoring the pulmonary inflammation progression. These results strongly suggest that [18F]17 has promising prospects as a CSF1R PET tracer, providing diagnostic opportunities for pulmonary inflammatory diseases.

Low dose optimization for total-body 2-[18F]FDG PET/CT imaging: a single-center study on feasibility based on body mass index stratification.

OBJECTIVES: Implementing personalization protocol in clinical routine necessitates diverse low-dose PET/CT scan protocols. This study explores the clinical feasibility of one-third (1/3) dose regimen and evaluates the diagnostic image quality and lesion detectability of BMI-based 1/3-injection doses for 2-[18F]FDG PET/CT imaging. METHODS: Seventy-four cancer patients underwent total-body 2-[18F]FDG PET/CT examination, with 37 retrospectively enrolled as full-dose group (3.7 MBq/kg) and 37 prospectively enrolled as the 1/3-dose group (1.23 MBq/kg). The 1/3-dose group was stratified by BMI, with an acquisition time of 5 min (G5), 6 min (G6), and 8 min (G8) for BMI < 25, 25 ≤ BMI ≤ 29, and BMI > 29, respectively. Image quality was subjectively and objectively assessed, and lesion detectability was quantitatively analyzed. RESULTS: Subjective assessments of 1/3-dose and full-dose PET images showed strong agreement among readers (κ > 0.88). In the 1/3-dose group, the Likert scores were above 4. G5, G6, and G8 showed comparable image quality, with G5 demonstrating higher lesion conspicuity than G6 and G8 (p = 0.045). Objective evaluation showed no significant differences in SUVmax, liver SUVmean and TBR between 1/3- and full-dose groups (p > 0.05). No statistical differences were observed in the SUVmax of primary tumor, SUVmean of liver and TBR across all BMI categories between the 1/3-dose and full-dose groups. Lesion detection rates showed no significant difference between the 1/3-dose (93.24%, 193/207) and full-dose groups (94.73%, 198/209) (p = 0.520). CONCLUSION: A BMI-stratified 1/3-dose regimen is a feasible low-dose alternative with clinically acceptable lesion detectability equivalent to full-dose protocol, potentially expanding the applicability of personalized protocols. CLINICAL RELEVANCE STATEMENT: This study demonstrated that BMI-stratified 1/3-dose regimens for [18F]FDG total-body PET/CT yielded equivalent outputs compared to the full-dose regimen, which aligns with clinical needs for personalization in dose and BMI. KEY POINTS: Currently, limited personalized low-dose total-body PET/CT protocols are available, particularly for patients with varied BMI. Reducing the radiotracer dose to 1/3 the standard demonstrated comparable image quality and lesion detectability equivalent to full dose. BMI-stratified 1/3-dose regimen is a clinically feasible low-dose alternative.

The earliest optimal timing for total-body 68Ga-fibroblast activation protein inhibitor-04 PET scans: an evidence-based single-centre study.

OBJECTIVES: To investigate the earliest optimal timing for positron emission tomography (PET) scans after 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) injection. METHODS: This prospective study enrolled patients who underwent 60-min dynamic 68Ga-FAPI-04 total-body PET/CT scans; the images were reconstructed at 10-min intervals (G0-10, G10-20, G20-30, G30-40, G40-50, and G50-60), and the [68Ga]Ga-FAPI-04 uptake patterns were evaluated. The standardised uptake value (SUV), liver signal-to-noise ratio (SNR), and lesion-to-background ratios (LBRs) for different time windows were calculated to evaluate image quality and lesion detectability. The period from 30 to 40 min was then split into overlapping 5-min intervals starting 1 min apart for further evaluation. G50-60 was considered the reference. RESULTS: A total of 30 patients with suspected malignant tumours were analysed. In the images reconstructed over 10-min intervals, longer acquisition times were associated with lower background uptake and better image quality. Some lesions could not be detected until G30-40. The lesion detection rate, uptake, and LBRs did not differ significantly among G30-40, G40-50, and G50-60 (all p > 0.05). The SUVmean and LBRs of primary tumours in the reconstructed images did not differ significantly among the 5-min intervals between 30 and 40 min; for metastatic and benign lesions, G34-39 and G35-40 showed significantly better SUVmean and LBR values than the other images. The G34-39 and G50-60 scans showed no significant differences in uptake, LBRs, or detection rates (all p > 0.05). CONCLUSION: The earliest optimal time to start acquisition was 34 min after injection of half-dose [68Ga]Ga-FAPI-04. CLINICAL RELEVANCE STATEMENT: This study evaluated 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) uptake patterns by comparing the image quality and lesion detection rate with 60-min dynamic [68Ga]Ga-FAPI-04 total-body PET/CT scans and identified the earliest optimal scan time after [68Ga]Ga-FAPI-04 injection. KEY POINTS: • A prospective single-centre study showed that the earliest optimal time point to start acquisition was 34 min after injection of half-dose [68Ga-fibroblast activation protein inhibitor-04 (68Ga]Ga-FAPI-04). • There were statistically significant differences in standardised uptake value, lesion-to-background ratios, and lesion detectability between scans before and after 34 min from the injection of [68Ga]Ga-FAPI-04, but these values did not change further from 34 to 60 min after injection. • With a reasonable acquisition time, the image quality could still meet diagnostic requirements.

A comprehensive value-based method for new nuclear medical service pricing: with case study of radium [223Ra] bone metastases treatment.

IMPORTANCE: Innovative nuclear medicine services offer substantial clinical value to patients. However, these advancements often come with high costs. Traditional payment strategies do not incentivize medical institutes to provide new services nor determine the fair price for payers. A shift towards a value-based pricing strategy is imperative to address these challenges. Such a strategy would reconcile the cost of innovation with incentives, foster transparent allocation of healthcare resources, and expedite the accessibility of essential medical services. OBJECTIVE: This study aims to develop and present a comprehensive, value-based pricing model for new nuclear medicine services, illustrated explicitly through a case study of the radium [223Ra] treatment for bone metastases. In constructing the pricing model, we have considered three primary value determinants: the cost of the new service, associated service risk, and the difficulty of the service provision. Our research can help healthcare leaders design an evidence-based Fee-For-Service (FFS) payment reference pricing with nuclear medicine services and price adjustments. DESIGN, SETTING AND PARTICIPANTS: This multi-center study was conducted from March 2021 to February 2022 (including consultation meetings) and employed both qualitative and quantitative methodologies. We organized focus group consultations with physicians from nuclear medicine departments in Beijing, Chongqing, Guangzhou, and Shanghai to standardize the treatment process for radium [223Ra] bone metastases. We used a specially designed 'Radium Nuclide [223Ra] Bone Metastasis Data Collection Form' to gather nationwide resource consumption data to extract information from local databases. Four interviews with groups of experts were conducted to determine the add-up ratio, based on service risk and difficulty. The study organized consultation meeting with key stakeholders, including policymakers, service providers, clinical researchers, and health economists, to finalize the pricing equation and the pricing result of radium [223Ra] bone metastases service. MAIN OUTCOMES AND MEASURES: We developed and detailed a pricing equation tailored for innovative services in the nuclear medicine department, illustrating its application through a step-by-step guide. A standardized service process was established to ensure consistency and accuracy. Adhering to best practice guidelines for health cost data analysis, we emphasized the importance of cross-validation of data, where validated data demonstrated less variation. However, it required a more advanced health information system to manage and analyze the data inputs effectively. RESULTS: The standardized service of radium [223Ra] bone metastases includes: pre-injection assessment, treatment plan, administration, post-administration monitoring, waste disposal and monitoring. The average duration for each stage is 104 min, 39 min, 25 min, 72 min and 56 min. A standardized monetary value for medical consumables is 54.94 yuan ($7.6), and the standardised monetary value (medical consumables cost plus human input) is 763.68 yuan ($109.9). Applying an agreed value add-up ratio of 1.065, the standardized value is 810.19 yuan ($116.9). Feedback from a consultation meeting with policymakers and health economics researchers indicates a consensus that the pricing equation developed was reasonable and well-grounded. CONCLUSION: This research is the first study in the field of nuclear medicine department pricing methodology. We introduce a comprehensive value-based nuclear medical service pricing method and use radium[223Ra] bone metastases treatment pricing in China as a case study. This study establishes a novel pricing framework and provides practical instructions on its implementation in a real-world healthcare setting.

Development of natural perfume as potential fungicide candidates: construction and biological evaluation of vanillin analogs bearing the 1,3,4-oxadiazole/1,3-thiazolidin-4-one fragments.

Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds 6j (29.73 µg/ml) and 7a (38.15 µg/ml) displayed excellent inhibitory activity against the spore of Fusarium solani. The inhibitory activity of compound 7d (10.53 µg/ml) against the spore of Alternaria solani was more than 42-fold that of vanillin. Compound 7a (37.54 µg/ml) showed better antifungal activity against the spore of B. cinerea than positive controls. The cytotoxicity assay confirmed that compounds 6k, 7a, and 7d showed good selectivity and less toxicity to normal mammalian cells.

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.

A head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MR in patients with nasopharyngeal carcinoma under different disease settings.

OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) are complementary in staging of nasopharyngeal carcinoma (NPC). The combination of MRI and functional imaging from PET in PET/MR is promising in NPC management. Diagnostic performance of PET/CT and PET/MR was compared in 46 patients with histologically confirmed NPC under different disease scenarios, including primary non-metastatic cases, primary metastatic cases, recurrence and/or metastasis after treatment, and post-treatment follow-up cases. SUBJECTS AND METHODS: Forty-six patients underwent both PET/CT and PET/MR in the same day. Primary tumor extension into risk-stratified anatomic structures, retropharyngeal and cervical lymph node metastasis, distant metastasis and post-treatment follow-up results, were compared. RESULTS: For high-risk structures, PET/MR detected two more sides of tensor/levator veli palatine muscle involvement, one more case of clivus involvement, and ruled out 12 false-positive sides of prevertebral muscle involvement by PET/CT. For medium-risk structures, PET/MR detected four more sides of medial pterygoid muscle involvement. For low-risk structures, abnormal signal on massa lateralis atlantis was detected by PET/MR. PET/MR detected 14 more positive retropharyngeal lymph nodes and more liver micrometastases than PET/CT. Overall, PET/MR changed two patients' T staging. CONCLUSION: Positron emission tomography/MR outperforms PET/CT in delineating muscle, skull-base bone, and nodal involvement, and identifying liver micrometastases, may serve as a single-step staging modality for NPC.

An artificial-intelligence-based age-specific template construction framework for brain structural analysis using magnetic resonance images.

It is an essential task to construct brain templates and analyze their anatomical structures in neurological and cognitive science. Generally, templates constructed from magnetic resonance imaging (MRI) of a group of subjects can provide a standard reference space for analyzing the structural and functional characteristics of the group. With recent development of artificial intelligence (AI) techniques, it is desirable to explore AI registration methods for quantifying age-specific brain variations and tendencies across different ages. In this article, we present an AI-based age-specific template construction (called ASTC) framework for longitudinal structural brain analysis using T1-weighted MRIs of 646 subjects from 18 to 82 years old collected from four medical centers. Altogether, 13 longitudinal templates were constructed at a 5-year age interval using ASTC, and tissue segmentation and substructure parcellation were performed for analysis across different age groups. The results indicated consistent changes in brain structures along with aging and demonstrated the capability of ASTC for longitudinal neuroimaging study.

PET vascular activity score for predicting new angiographic lesions in patients with Takayasu arteritis: a Chinese cohort study.

OBJECTIVE: To investigate the ability of 18F-fluorodeoxyglucose PET/CT to predict new lesions in Takayasu arteritis. METHODS: Eighty-two Chinese patients with newly diagnosed Takayasu arteritis were recruited. Their clinical characteristics, serum biomarkers and imaging results were recorded at baseline and every visit. They were followed up for at least 2 years. New angiographic lesions were evaluated by magnetic resonance angiography. Baseline PET vascular activity scores (PETVAS) for predicting new lesions were evaluated. RESULTS: At baseline, a moderate correlation was observed between PETVAS and ESR (r = 0.74, P < 0.01) and CRP level (r = 0.69, P < 0.01). Overall, 18 (22%) patients showed new lesions on imaging during a median follow-up time of 36 months. The median time to the first occurrence of new lesions was 18 months. Compared with patients without new lesions, the patients with new lesions included more female patients (67.2% vs 94.4%, P = 0.03), patients with higher ESR values (20 vs 49, P = 0.02) and patients with active disease (62.5% vs 94.4%, P < 0.01). Multivariate Cox regression analysis revealed PETVAS was an independent risk factor for new angiographic lesions (PETVAS ≥8, hazard ratio = 7.56; 95% CI 2.20, 26.01, P < 0.01) with adjustment of age, sex, chest pain, ESR and Physician Global Assessment. Furthermore, patients with PETVAS ≥8 at baseline were more likely to experience adverse events including arterial ischaemic events during the follow-up. CONCLUSION: PETVAS showed good performance in predicting new lesions in Takayasu arteritis.

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.

An artificial intelligence-driven image quality assessment system for whole-body [18F]FDG PET/CT.

PURPOSE: Image quality control is a prerequisite for applying PET/CT. This study aimed to develop an artificial intelligence-driven real-time and accurate whole-body [18F]FDG PET/CT image quality assessment system. METHODS: This study included 173 patients (age, 59 ± 12 years; 66.3% males) with whole-body [18F]FDG PET/CT imaging. Images of ten patients were used as an educational set. Images of the rest 163 patients were reconstructed to 952 images by simulating several scanning times and randomly split into training (60%, 98 patients, 578 images), validation (20%, 33 patients, 192 images), and test (20%, 32 patients,182 images) sets. Two experienced physicians (R1 and R2) independently assessed the image quality of thorax, abdomen, and pelvis region twice (R1a and b; R2a and b), 1 month apart, using a 5-point Likert scale. Objective image quality metrics were extracted from the mediastinal blood pool, three liver levels, and the bilateral gluteus maximus. The developed convolutional neural networks for image quality assessment (IQA-CNNs) generated the subjective quality scores and objective image metrics. The IQA-CNNs and physicians' performances were compared for localization accuracy, score agreement, and process time. RESULTS: The physicians demonstrated good inter- and intra-rater subjective assessment agreement, with kappa coefficients (R1a vs. R2a, R1a vs. R1b, R2a vs. R2b, and R1a vs. R2b) of 0.78, 0.77, 0.76, and 0.80. The IQA-CNNs and R1 or R2 agreed in the subjective assessments, with kappa coefficients of 0.79 and 0.78. IQA-CNNs and R1 or R2 also agreed in their objective image quality assessment (ICC > 0.60). The IQA-CNNs evaluation speed was 200 times faster than the manual assessment. CONCLUSION: An automated system for rapid assessment of [18F]FDG PET/CT image quality was developed, showing comparable performance to senior physicians. The system generates a comprehensive and detailed image quality assessment report, including subjective visual scores and objective image metrics for various anatomical regions.

An exploration of the feasibility and clinical value of half-dose 5-h total-body 18F-FDG PET/CT scan in patients with Takayasu arteritis.

PURPOSE: To explore the feasibility and clinical value of 5-h delayed 18F-fluorodeoxyglucose (18F-FDG) total-body (TB) positron emission tomography/computed tomography (PET/CT) in patients with Takayasu arteritis (TA). METHODS: This study included nine healthy volunteers who underwent 1-, 2.5-, and 5-h triple-time TB PET/CT scans and 55 patients with TA who underwent 2- and 5-h dual-time TB PET/CT scans with 1.85 MBq/kg 18F-FDG. The liver, blood pool, and gluteus maximus muscle signal-to-noise ratios (SNRs) were calculated by dividing the SUVmean by its standard deviation to evaluate imaging quality. TA lesions' 18F-FDG uptake was graded on a three-point scale (I, II, III), with grades II and III considered positive lesions. Lesion-to-blood maximum standardised uptake value (SUVmax) ratio (LBR) was calculated by dividing the lesion SUVmax by the blood pool SUVmax. RESULTS: The liver, blood pool, and muscle SNR of the healthy volunteers at 2.5- and 5-h were similar (0.117 and 0.115, respectively, p = 0.095). We detected 415 TA lesions in 39 patients with active TA. The average 2- and 5-h scan LBRs were 3.67 and 7.59, respectively (p < 0.001). Similar TA lesion detection rates were noted in the 2-h (92.0%; 382/415) and 5-h (94.2%; 391/415) scans (p = 0.140). We detected 143 TA lesions in 19 patients with inactive TA. The 2- and 5-h scan LBRs were 2.99 and 5.71, respectively (p < 0.001). Similar positive detection rates in inactive TA were noted in the 2-h (97.9%; 140/143) and 5-h (98.6%; 141/143) scans (p = 0.500). CONCLUSION: The 2- and 5-h 18F-FDG TB PET/CT scans had similar positive detection rates, but both combined could better detect inflammatory lesions in patients with TA.

124I-Labeled Immuno-PET Targeting hTREM2 for the Diagnosis of Gastric Carcinoma.

Low ß-2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake in gastric mucinous adenocarcinoma may cause false-negative diagnosis and erroneous staging. Thus, there is an urgent need for developing tumor-specific imaging agents in gastric cancer diagnostics. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein expressed on the surface of tumor-associated macrophages (TAMs) and is considerably overexpressed in tumor tissues. This study aimed to develop new human TREM2 (hTREM2)-targeting imaging agents to diagnose and monitor gastric cancer. We established a cell line, MGC803, with upregulated expression of hTREM2, at the cell surface. We produced a monoclonal antibody (5-mAb) against hTREM2 by immunizing mice with the hTREM2 antigen to obtain the antibody fragment 5-F(ab')2 using an immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS). Another anti-TREM2-mAb (clone 237920) and its fragment anti-TREM2-F(ab')2 were employed for the comparative study in vitro and in vivo. After 124I labeling, we constructed the probes: 124I-5-mAb, 124I-5-F(ab')2, 124I-anti-TREM2-mAb, and 124I-anti-TREM2-F(ab')2. We found that 5-mAb exhibited higher hTREM2 affinity and slower blood clearance than anti-TREM2-mAb, whose corresponding F(ab')2 fragments demonstrated the same trend. The micro-PET/CT revealed that 124I-5-F(ab')2 exhibited advantages of tumor enrichment and fast metabolism. The biodistribution study results were consistent with those of micro-PET/CT. Among the four tracers, 124I-5-F(ab')2 was the most suitable specific radiotracer for targeting hTREM2 and displayed potential utility as a tumor-imaging tracer for diagnosing gastric carcinoma.