Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

Objective:To explore the effectiveness of 18F-deuterated-Florbetapir (D3FSP) PET/CT imaging in detecting β-amyloid (Aβ) deposition in the brain and its correlation with plasma biomarkers. Methods:A retrospective analysis was conducted on 79 patients (32 males, 47 females; age(66±7)years) who underwent 18F-D3FSP PET/CT imaging from June 2022 to November 2023 at the First Affiliated Hospital, Guangzhou Medical University, as a part of the Greater Bay Area Healthy Aging Brain Longitudinal Cohort Study (GHABS). Based on the Alzheimer′s Disease Neuroimaging Initiative cohort standard protocol, patients were categorized into cognitively unimpaired (CU) group, mild cognitive impairment (MCI) group, and Alzheimer′s disease (AD) group. Brain regions were segmented using the AW workstation and the SUV ratio (SUVR) was calculated with the cerebellum as the reference region. One-way analysis of variance, Bonferroni correction and Pearson correlation analysis were used to analyze data. The ROC curve analysis was used to analyze the cut-off value and the diagnostic efficacy of SUVR. Results:There were 48, 15 and 16 cases in CU, MCI and AD groups respectively. During the transition from CU to MCI and then to AD, there was a rising trend in SUVR ( F values: 11.15-22.38, all P<0.001) across the whole brain and various brain regions (bilateral frontal lobes, bilateral anterior cingulate gyrus, bilateral precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes). SUVRs of the right anterior cingulate gyrus and bilateral precuneus were different between the CU and MCI groups (all P<0.017), and those of bilateral frontal lobes, right precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes were different between the MCI and AD groups (all P<0.017). SUVRs of brain regions were negatively correlated with cognitive scale scores ( r values: from -0.57 to -0.37, all P<0.001), and were positively correlated with plasma phosphorylated tau181 (p-tau181, r values: 0.50-0.61, all P<0.001). The ROC curve analysis suggested that the cut-off value of SUVR in the precuneus for distinguishing CU from AD was 1.20, with the AUC, sensitivity, specificity and accuracy of 0.85, 12/16, 91.7%(44/48)and 87.5%(56/64), respectively. Conclusion:18F-D3FSP PET/CT imaging has good clinical application value in assessing the deposition sites and the extent of Aβ in the brain, which is related to clinical cognition and plasma p-tau181 level.

Objective:To evaluate the diagnostic efficacy of the novel prostate specific membrane antigen (PSMA)-targeted PET imaging agent 18F-AlF-P16-093 in combination with multiparametric MRI (mpMRI) for prostate cancer (PCa), and to explore its application in guiding transperineal puncture biopsy. Methods:A retrospective analysis was conducted on the clinical and pathological data of 36 patients diagnosed as PCa (age: 68-76 years) who underwent 18F-AlF-P16-093 PET/CT and mpMRI examinations at the First Affiliated Hospital of Guangzhou Medical University from August 2023 to March 2024. The entire prostate was divided into 12 regions based on biopsy localization. Imaging evaluations were performed using PET/CT and mpMRI at the lesion level, with biopsy pathology as the gold standard. The correlations between mpMRI scores, PET/CT scores and pathological diagnosis results were evaluated by Phi coefficient analysis. Diagnostic efficacy was assessed by ROC curve analysis. Logistic regression was used to determine the impact of bleeding on image interpretation. Results:18F-AlF-P16-093 PET/CT showed a moderate positive correlation with pathological diagnosis result ( Phi=0.415, P<0.001), which was superior to mpMRI ( Phi=0.338, P<0.001). The diagnostic efficacy of PET single-modality model was superior to mpMRI in all indicators. The combination of 18F-AlF-P16-093 PET/CT with mpMRI significantly improved diagnostic specificity and positive predictive value, with the diagnostic specificity of the PET+ T 2 weighted imaging (WI)+ diffusion WI (DWI) and PET+ T 2WI+ DWI+ apparent diffusion coefficient (ADC) combinations exceeding 90%, and the positive predictive value exceeding 80%. Bleeding did not significantly affect the diagnosis of PCa by mpMRI and PET/CT (odds ratio ( OR): 0.463-0.785, all P>0.05). Conclusion:18F-AlF-P16-093 PET/CT is superior to mpMRI in the detection and diagnostic efficacy of PCa lesions, and the combination of 18F-AlF-P16-093 PET with mpMRI can further improve diagnostic specificity and positive predictive value, which is of guiding significance for targeted prostate biopsy.

Purpose To investigate the effect of shortening the acquisition time of 18F-D6-AV133 PET/CT on image quality and diagnostic efficacy in Parkinson's disease.Materials and Methods A total of 51 participants(27 of Parkinson's disease,24 of healthy-controls)from the First Affiliated Hospital of Guangzhou Medical University from October 2021 to June 2022 were retrospectively selected.Images were obtained after the injection of the tracer 18F-D6-AV133(371.04±16.30)MBq for 60 min,with collection times of 10 min.Four sets of images were reconstructed using CT attenuation correction with acquisition times of 3,5,7 and 10 min.Semi-quantitative analysis was performed on the PET images,calculating the striatum-to-occipital lobe standardized uptake value ratio(SUVR).Two physicians independently conducted qualitative evaluations for each image group.The differences of SUVR and visual score results among four sets of images were performed.The optimal critical value of SUVR was obtained by analyzing the receiver operating characteristic curve of the subjects.Results The visual analysis of image quality had a strong consistency between the two doctors(ICC=0.853,P<0.001).The images with acquisition time of 5 min could reach the common quality level in clinical work,accounting for 78.4%(40/51).The semi-quantitative results of image quality showed that there was no significant difference between SUVR and diagnostic efficiency obtained by acquisition time 5 min and 10 min(Z=1.821,P=0.069),and the best critical value of the two groups was equal to 3.Therefore,properly shortening the acquisition time had no effect on the diagnosis of Parkinson's disease.Conclusion With the development and advancement of technical equipment,PET image quality is gradually improving and the scanning time is also gradually shortening.The acquisition time for 18F-D6-AV133 can be shortened from the conventional 10 min to 5 min.

Purpose To investigate the diagnosis and staging performance of 18F-FAPI-42 PET/CT compared to 18F-FDG PET/CT in primary hepatic tumours. Materials and Methods We performed a retrospective study including all primary hepatic tumours patients who underwent both 18F-FAPI-42 and 18F-FDG PET/CT scans within two weeks at the First Affiliated Hospital of Guangzhou Medical University from October 2020 to May 2023. With histopathologic proof (surgical resection and/or percutaneous biopsies) or multimodality radiographic follow-up (CT/MRI-enhanced) as the final diagnostic reference standard. The maximum standard uptake value,tumor-to-background ratio and diagnostic rates (positive lesion/total lesion) between 18F-FAPI-42 and 18F-FDG were compared. Results Thirty-four primary hepatic tumours patients were enrolled in this study,including 27 hepatocellular carcinoma,5 intrahepatic cholangiocarcinoma and 2 combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma. It was found that 18F-FAPI-42 PET/CT significantly outperformed 18F-FDG in diagnosing intrahepatic lesions and lymph node metastases (intrahepatic lesions:93.33％ vs. 52.22％,P<0.001;lymph node metastases:100％ vs. 87.50％,P=0.021). The detection rates for distant metastases were comparable between the two radioactive tracers (100％ vs. 96.20％,P>0.05). 18F-FAPI-42 showed higher maximum standard uptake value and tumor-to-background ratio in intrahepatic lesions,regional lymph node metastases,bone and peritoneal metastases compared to 18F-FDG (Z=-5.261--1.183,all P<0.05). For primary hepatic tumours initial staging,18F-FAPI-42 PET/CT upstaged the T stage in 20.8％ (5/24) of patients,the N stage in 8.3％ (2/24) and the M stage in 8.3％ (2/24) of patients,consistent with multimodal imaging diagnostic results. The evaluation of post-treatment patient outcomes showed that 18F-FAPI-42 had a detection rate of 92.86％ (13/14) for hepatic tumours recurrence,higher than 18F-FDG (64.28％,9/14). 18F-FAPI-42 identified more recurrent primary lesions and intrahepatic metastatic foci,demonstrating greater sensitivity than 18F-FDG. Conclusion The diagnostic efficacy of 18F-FAPI-42 PET/CT for primary hepatic tumours is significantly better than 18F-FDG,showing excellent performance in the staging and restaging of primary hepatic tumours,which suggesting that the application of 18F-FAPI-42 is helpful to improve the clinical management of primary hepatic tumours patients.

Purpose To investigate the diagnosis and staging performance of 18F-FAPI-42 PET/CT compared to 18F-FDG PET/CT in primary hepatic tumours. Materials and Methods We performed a retrospective study including all primary hepatic tumours patients who underwent both 18F-FAPI-42 and 18F-FDG PET/CT scans within two weeks at the First Affiliated Hospital of Guangzhou Medical University from October 2020 to May 2023. With histopathologic proof (surgical resection and/or percutaneous biopsies) or multimodality radiographic follow-up (CT/MRI-enhanced) as the final diagnostic reference standard. The maximum standard uptake value,tumor-to-background ratio and diagnostic rates (positive lesion/total lesion) between 18F-FAPI-42 and 18F-FDG were compared. Results Thirty-four primary hepatic tumours patients were enrolled in this study,including 27 hepatocellular carcinoma,5 intrahepatic cholangiocarcinoma and 2 combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma. It was found that 18F-FAPI-42 PET/CT significantly outperformed 18F-FDG in diagnosing intrahepatic lesions and lymph node metastases (intrahepatic lesions:93.33％ vs. 52.22％,P<0.001;lymph node metastases:100％ vs. 87.50％,P=0.021). The detection rates for distant metastases were comparable between the two radioactive tracers (100％ vs. 96.20％,P>0.05). 18F-FAPI-42 showed higher maximum standard uptake value and tumor-to-background ratio in intrahepatic lesions,regional lymph node metastases,bone and peritoneal metastases compared to 18F-FDG (Z=-5.261--1.183,all P<0.05). For primary hepatic tumours initial staging,18F-FAPI-42 PET/CT upstaged the T stage in 20.8％ (5/24) of patients,the N stage in 8.3％ (2/24) and the M stage in 8.3％ (2/24) of patients,consistent with multimodal imaging diagnostic results. The evaluation of post-treatment patient outcomes showed that 18F-FAPI-42 had a detection rate of 92.86％ (13/14) for hepatic tumours recurrence,higher than 18F-FDG (64.28％,9/14). 18F-FAPI-42 identified more recurrent primary lesions and intrahepatic metastatic foci,demonstrating greater sensitivity than 18F-FDG. Conclusion The diagnostic efficacy of 18F-FAPI-42 PET/CT for primary hepatic tumours is significantly better than 18F-FDG,showing excellent performance in the staging and restaging of primary hepatic tumours,which suggesting that the application of 18F-FAPI-42 is helpful to improve the clinical management of primary hepatic tumours patients.

Objective:A high performance liquid chromatography (HPLC) method was developed to determine the enzymatic activity of CD38 in blood, which was the major enzyme responsible for consuming nicotinamide adenine dinucleotide (NAD). Additionally, the study aimed to detect the differences in CD38 enzymatic activity among individuals of varying ages and health statuses.Methods:A 50 μl whole blood matrix and enzyme reaction substrate of 150 μl β-NAD at a concentration of 500 μmol/L were selected for the analysis. To eliminate the impact of endogenous β-NAD, the whole blood sample was pre-incubated at 37 ℃ for 20 minutes before adding the substrate. The reaction was terminated by perchloric acid (PCA) after incubation at 37 ℃ for 40 min. The change in product nicotinamide (NAM) before and after the enzymatic reaction was measured by HPLC to calculate the CD38 activity. The linearity, limit of detection, limit of quantification, precision, and stability of the method were evaluated. The CD38 enzymatic activities in 60 healthy volunteers and 30 colorectal cancer patients in blood were determined by the developed method.Results:Pre-incubation at 37 ℃ for 20 minutes eliminated the effect of endogenous β-NAD. The correlation coefficient of NAM was 0.999 in the concentration range of 0.1-3.2 μmol/L, with limit of detection of 0.5 nmol/L and limit of quantification of 2.1 nmol/L. The average within-run imprecision ( CV) and total CV were 3.22%-4.03% and 2.91%-4.70%, respectively. The recovery rate ranged from 94.82% to 96.81%. The CD38 activity of whole blood was stable by storage at 4 ℃ for 48 hours, storage at room temperature for 8 hours, thawing of frozen whole blood at room temperature for 2 hours, or repeated freeze-thawing three times. NAM, NAD standards, and pre-treatment samples were stable after 48 hours at 4 ℃ and 8 hours at room temperature. CD38 activity gradually decreased with increasing concentration of the added CD38 inhibitor 4-aminoquinoline derivative (78c). Measurement of 60 healthy physical examination population samples showed significantly higher CD38 enzyme activity in the elderly group than that in the young group ( t=-2.776, P=0.007) and measurement of 30 colorectal cancer patients showed significantly higher CD38 enzyme activity than that in healthy people ( t=-2.572, P=0.012). Conclusion:The established HPLC method for determining CD38 enzymatic activity is characterized by its simplicity, efficiency, accuracy, and reproducibility. This technique serves as a valuable tool for investigating aging and aging-related diseases.