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.

SPECT/CT imaging: quantifying 99mTc-MDP concentration in the spine and pelvis.

OBJECTIVE: This study aimed to identify a relatively robust SUV for guiding clinical practice through quantitative measurement and comparison of various normalization methods based on the SUV of 99mTc-MDP in the normal spine and pelvis using an integrated SPECT/CT scanner. METHODS: Between June 2017 and September 2019, a total of 500 oncology patients (mean age, 60.9; men, 66.0%) who underwent bone SPECT/CT scans with 99mTc-MDP were enrolled in this retrospective study. The mean SUV (SUVmean) of 4962 spinal and pelvic bones was calculated based on the patients' body weight (BW), lean body mass (LBM), bone mineral content (BMC), body surface area (BSA), and body mass index (BMI), defined as SUVbw, SUVlbm, SUVbmc, SUVbsa, and SUVbmi, respectively. The coefficients of variation (CoVs) of the aforementioned parameters were compared, and the correlation and multiple linear regression analyses were used to compare the extent to which these parameters were affected by sex, age, height, weight, BMI, and CT values. RESULTS: The average SUVs in the normal spine and pelvis displayed a relatively wide variability: 4.573 ± 1.972 for SUVbw, 3.555 ± 1.517 for SUVlbm, 0.163 ± 0.071 for SUVbmc, 0.124 ± 0.052 for SUVbsa, and 1.668 ± 0.732 for SUVbmi. In general, SUVbsa had relatively lowest CoV (42.1%) in all vertebrae and pelvis compared with other SUVs. For correlation analyses, all SUVs displayed weak but significant correlations with age and CT values. For regression analyses, SUVbsa was influenced only by age, BMI, and CT values independently. The effects of these variables on SUVbsa were all smaller than those on conventional SUVbw. CONCLUSIONS: The SUVs of 99mTc-MDP in normal bone derived from quantitative bone SPECT/CT could serve as a reference for evaluating tumor bone metastasis, but it should be assessed on a site-specific basis. SUVbsa exhibited superior robustness among all the SUV normalization variations, indicating potential clinical applications.

Comparison of the Accuracy of a Deep Learning Method for Lesion Detection in PET/CT and PET/MRI Images.

PURPOSE: Develop a universal lesion recognition algorithm for PET/CT and PET/MRI, validate it, and explore factors affecting performance. PROCEDURES: The 2022 AutoPet Challenge's 1014 PET/CT dataset was used to train the lesion detection model based on 2D and 3D fractional-residual (F-Res) models. To extend this to PET/MRI, a network for converting MR images to synthetic CT (sCT) was developed, using 41 sets of whole-body MR and corresponding CT data. 38 patients' PET/CT and PET/MRI data were used to verify the universal lesion recognition algorithm. Image quality was assessed using signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Total lesion glycolysis (TLG), metabolic tumor volume (MTV), and lesion count were calculated from the resultant lesion masks. Experienced physicians reviewed and corrected the model's outputs, establishing the ground truth. The performance of the lesion detection deep-learning model on different PET images was assessed by detection accuracy, precision, recall, and dice coefficients. Data with a detection accuracy score (DAS) less than 1 was used for analysis of outliers. RESULTS: Compared to PET/CT, PET/MRI scans had a significantly longer delay time (135 ± 45 min vs 61 ± 12 min) and lower SNR (6.17 ± 1.11 vs 9.27 ± 2.77). However, CNR values were similar (7.37 ± 5.40 vs 5.86 ± 6.69). PET/MRI detected more lesions (with a mean difference of -3.184). TLG and MTV showed no significant differences between PET/CT and PET/MRI (TLG: 119.18 ± 203.15 vs 123.57 ± 151.58, p = 0.41; MTV: 36.58 ± 57.00 vs 39.16 ± 48.34, p = 0.33). A total of 12 PET/CT and 14 PET/MRI datasets were included in the analysis of outliers. Outlier analysis revealed PET/CT anomalies in intestines, ureters, and muscles, while PET/MRI anomalies were in intestines, testicles, and low tracer uptake regions, with false positives in ureters (PET/CT) and intestines/testicles (PET/MRI). CONCLUSION: The deep learning lesion detection model performs well with both PET/CT and PET/MRI. SNR, CNR and reconstruction parameters minimally impact recognition accuracy, but delay time post-injection is significant.

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.

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.

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.

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.

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.

Multiparametric evaluation of mediastinal lymph node metastases in clinical T0-T1c stage non-small-cell lung cancers.

OBJECTIVES: This study aimed to determine the predictive factors of lymph node metastases in clinical T0-T1c stage non-small-cell lung cancers, so as to help making surgical strategy. METHODS: From January 2016 to December 2017, patients with clinical T0-T1c stage non-small-cell lung cancers were retrospectively reviewed. We elucidated the lymph node metastatic incidence and distribution according to the primary tumour radiographic findings and maximal standard uptake values, and extracted the associated clinicopathological factors. Univariable and multivariable logistic regressions were used to identify independent predictive parameters for lymph node metastases. The performance of predictive model was evaluated using receiver operating characteristic analysis. RESULTS: A total of 517 patients were included. Seventy-two patients had lymph node metastases. Among patients with pure ground-glass nodule and solid component size ≤10 mm, none had any lymph node metastasis. Multivariable logistic regression analysis demonstrated that age, carcinoembryonic antigen level, solid component size, consolidation-tumour ratio and tumour maximal standard uptake values were independent predictors of lymph nodal metastases. Receiver operating characteristic analyses indicated that the area under the curve of predictive model in evaluating lymph node metastases was 0.838 (95% CI 0.791-0.886). CONCLUSIONS: Younger age, elevated carcinoembryonic antigen level, larger solid component size, higher consolidation-tumour ratio and tumour maximal standard uptake values were associated with lymph node involvement. Employing such a predictive model in the future may affect the surgical option of lymph node excision for patients in cT1 stage non-small-cell lung cancer.

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.

Phantom study and clinical application of total-body 18F-FDG PET/CT imaging: How to use small voxel imaging better?

BACKGROUND: Conventional PET/CT imaging reconstruction is typically performed using voxel size of 3.0-4.0 mm in three axes. It is hypothesized that a smaller voxel sizes could improve the accuracy of small lesion detection. This study aims to explore the advantages and conditions of small voxel imaging on clinical application. METHODS: Both NEMA IQ phantom and 30 patients with an injected dose of 3.7 MBq/kg were scanned using a total-body PET/CT (uEXPLORER). Images were reconstructed using matrices of 192 × 192, 512 × 512, and 1024 × 1024 with scanning duration of 3 min, 5 min, 8 min, and 10 min, respectively. RESULTS: In the phantom study, the contrast recovery coefficient reached the maximum in matrix group of 512 × 512, and background variability increased as voxel size decreased. In the clinical study, SUVmax, SD, and TLR increased, while SNR decreased as the voxel size decreased. When the scanning duration increased, SNR increased, while SUVmax, SD, and TLR decreased. The SUVmean was more reluctant to the changes in imaging matrix and scanning duration. The mean subjective scores for all 512 × 512 groups and 1024 × 1024 groups (scanning duration ≥ 8 min) were over three points. One false-positive lesion was found in groups of 512 × 512 with scanning duration of 3 min, 1024 × 1024 with 3 min and 5 min, respectively. Meanwhile, the false-negative lesions found in group of 192 × 192 with duration of 3 min and 5 min, 512 × 512 with 3 min and 1024 × 1024 with 3 min and 5 min were 5, 4, 1, 4, and 1, respectively. The reconstruction time and storage space occupation were significantly increased as the imaging matrix increased. CONCLUSIONS: PET/CT imaging with smaller voxel can improve SUVmax and TLR of lesions, which is advantageous for the diagnosis of small or hypometabolic lesions if with sufficient counts. With an 18F-FDG injection dose of 3.7 MBq/kg, uEXPLORER PET/CT imaging using matrix of 512 × 512 with 5 min or 1024 × 1024 with 8 min can meet the image requirements for clinical use.

Sex Differences in Coronary Inflammation and Atherosclerosis Phenotypes in Response to Imaging Marker of Stress-Related Neural Activity.

BACKGROUND: Sex-specific differences in coronary phenotypes in response to stress have not been elucidated. This study investigated the sex-specific differences in the coronary computed tomography angiography-assessed coronary response to mental stress. METHODS: This retrospective study included patients with coronary artery disease and without cancer who underwent resting 18F-fluorodexoyglucose positron emission tomography/computed tomography and coronary computed tomography angiography within 3 months. 18F-flourodeoxyglucose resting amygdalar uptake, an imaging biomarker of stress-related neural activity, coronary inflammation (fat attenuation index), and high-risk plaque characteristics were assessed by coronary computed tomography angiography. Their correlation and prognostic values were assessed according to sex. RESULTS: A total of 364 participants (27.7% women and 72.3% men) were enrolled. Among those with heightened stress-related neural activity, women were more likely to have a higher fat attenuation index (43.0% versus 24.0%; P=0.004), while men had a higher frequency of high-risk plaques (53.7% versus 39.3%; P=0.036). High amygdalar 18F-flourodeoxyglucose uptake (B-coefficient [SE], 3.62 [0.21]; P<0.001) was selected as the strongest predictor of fat attenuation index in a fully adjusted linear regression model in women, and the first-order interaction term consisting of sex and stress-related neural activity was significant (P<0.001). Those with enhanced imaging biomarkers of stress-related neural activity showed increased risk of major adverse cardiovascular event both in women (24.5% versus 5.1%; adjusted hazard ratio, 3.62 [95% CI, 1.14-17.14]; P=0.039) and men (17.2% versus 6.9%; adjusted hazard ratio, 2.72 [95% CI, 1.10-6.69]; P=0.030). CONCLUSIONS: Imaging-assessed stress-related neural activity carried prognostic values irrespective of sex; however, a sex-specific mechanism linking psychological stress to coronary plaque phenotypes existed in the current hypothesis-generating study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05545618.

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 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.

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.

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.