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Objective:To prepare specific molecular probe 18F-AlF-1, 4, 7-triazacylononane-1, 4, 7-triacetic acid-(polyethylene glycol) 4-ZD2 ( 18F-AlF-NOTA-PEG 4-ZD2) for targeting extradomain-B fibronectin (EDB-FN), and evaluate its properties in vitro and in vivo. Methods:18F-AlF-NOTA-PEG 4-ZD2 was prepared by one-step chelation labeling with Al 18F. The radiochemical purity and in vitro stability were determined by high performance liquid chromatography (HPLC). The partition coefficient (logP) of 18F-AlF-NOTA-PEG 4-ZD2 was evaluated, and the cell uptake experiment was carried out (triple-negative breast cancer (MDA-MB-231) cells (1×10 6/tube) were divided into 3 groups ( n=3 per group); positive group, inhibition group, control group). MicroPET imaging was performed on MDA-MB-231 bearing nude mice ( n=3) after 18F-AlF-NOTA-PEG 4-ZD2 injection (30, 60, 90, 120 min) and compared with blocking group ( n=3, NOTA-PEG 4-ZQ 2 was preinjected at 0.5 h before 18F-AIF-NOTA-PEG a-ZD2 injection). Independent-sample t test was used to analyze the data. Results:18F-AlF-NOTA-PEG 4-ZD2 was successfully prepared. The optimized radiochemical yield was (33.8±2.1)% (undecay corrected, n=8) and the radiochemical purity was >96%. After incubating 120 min at 37 ℃, the radiochemical purity of 18F-AlF-NOTA-PEG 4-ZD2 in human serum and PBS was >93%, indicating its good stability in vitro. The specific activity was (11.1±3.2) GBq/μmol, and logP was -1.43±0.05. The uptake value of tumor cells was (1.77±0.28) percentage applied activity (%AR)/10 6 cells at 120 min post-injection in positive group, and the total uptake value of the inhibition group was (0.76±0.07) %AR/10 6 cells ( t=4.30, P=0.032). MicroPET imaging in tumor bearing nude mice showed that 18F-AlF-NOTA-PEG 4-ZD2 was mainly metabolized by the liver and kidneys. The tumor uptake value was (1.94±0.21) percentage activity of injection dose per gram of tissue (%ID/g) at 60 min post-injection and the tumor/muscle ratio was 3.80±0.25 at 90 min post-injection in the experimental group, while the tumor uptake value of tumor bearing nude mice in the blocking group was (0.43±0.09) %ID/g at 60 min post-injection ( t=3.18, P=0.006). Conclusions:18F-AlF-NOTA-PEG 4-ZD2 can be prepared simply with high labeling rate and good stability in vitro, with high tumor uptake and tumor/muscle ratio in microPET imaging, and good specificity and long tumor residence time. The probe has good application prospect in breast cancer with high expression of fibronectin subtype EDB-FN.
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Objective:To evaluate the value of 18F-FDG PET/CT in the diagnosis and treatment of primary breast lymphoma (PBL). Methods:Clinical data and 18F-FDG PET/CT imaging data of 6 patients (all females, age 46-79 years) with pathologically diagnosed primary breast diffuse large B cell lymphoma (PB-DLBCL) in Xishan People′s Hospital of Wuxi City and Affiliated Hospital of Jiangnan University from July 2015 to October 2021 were analyzed retrospectively. A total of 10 18F-FDG PET/CT scans were done for primary staging (6 scans of 6 patients), evaluation of treatment response (3 scans of 2 patients), and recurrence detection (1 scan of 1 patient). 18F-FDG PET/CT image analysis was performed qualitatively (visually) and semi-quantitatively (SUV max). Treatment response was evaluated by Deauville scores. Results:All 6 patients were diagnosed pathologically as PB-DLBCL (3 patients by core needle biopsy, 3 patients by biopsy after lumpectomy). All 6 patients were staged using baseline 18F-FDG PET/CT before chemotherapy. For 3 patients diagnosed by core needle biopsy, baseline 18F-FDG PET/CT showed unilateral breast lesion with high FDG uptake (SUV max: 23.0, 52.9, and 33.6). For 3 postoperative patients, baseline 18F-FDG PET/CT showed flocculent soft tissue density in the operative area with low FDG uptake (SUV max: 3.4, 2.2 and 2.0). Patient No.2 showed a large left breast mass with left axillary lymph node involvement by baseline PET/CT, and multiple nodular uptakes in bilateral breast (Deauville score of 4) after 4 courses of chemotherapy and negative result (Deauville score of 1) after 3 courses of new chemotherapy regimens by PET/CT. Patient No.4 showed right breast lesion and right axillary lymph nodes by routine preoperative imaging examination, but left breast lesion by postoperative PET/CT. According to the results of 18F-FDG PET/CT, patient No.4 was with complete response (Deauville score of 1) after treatment, but recurrence (Deauville score of 5) occurred after 7 months follow-up. Conclusion:18F-FDG PET/CT can play an important role in every step of management (diagnosis and staging, treatment response evaluation and detection of recurrence) in patients with PB-DLBCL.
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Objective:To prepare 18F-Alfatide Ⅱ automatically based on the improved CFN-100 fluorine multifunctional module and assess its PET/CT imaging in prostate cancer patients. Methods:A certain volume (200-500 μl) of fluoride ion was separated into the reaction tube by a fluoride ion separator and reacted with the labeled precursor l, 4, 7-triazacylononane-1, 4, 7-triacetic acid-E[(polyethylene glycol) 4-cyclo(Arg-Gly-Asp- D-Phe-Tyr)] 2(NOTA-E[PEG 4-c(RGDfk)] 2) (lyophilized kit). In the aqueous phase, 18F was chelated with aluminum. After being separated and purified by C18 column, 18F-Alfatide Ⅱ was prepared automatically. The radiochemical yield and its quality were analyzed. Quality control was carried out and 18F-Alfatide Ⅱ PET/CT imaging was performed in 2 patients (72 and 66 years old)with prostate cancer. Results:18F-Alfatide Ⅱ was prepared automatically by the improved CFN-100 fluorine multifunctional module combined with a double channel-fluorine ion separation device. 18F-Alfatide Ⅱ was synthetized in about 30 min, with radiochemical yield of (28±3)% (non-decay corrected, n=6). The radiochemical purity of the product was more than 98%, the specific activity was 2.8×10 7 MBq/mmol and the nuclear purity was >99%. PET/CT imaging of 2 patients showed that 18F-Alfatide Ⅱ were highly concentrated in prostate cancer lesions with the maximum standardized uptake value (SUV max) of 35.6 and 5.0, respectively. Conclusion:18F-Alfatide Ⅱ can be prepared successfully by improved CFN-100 fluorine multifunctional module with stable synthesis method, short synthesis time and high radiochemical yield, which can be highly concentrated in prostate cancer.
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Objective To evaluate the diagnostic efficiency and prognostic value of 18F-fluorodeoxyglucose (FDG) PET/CT for response assessment after treatment in patients with diffuse large B-cell lymphoma (DLBCL) when using the Deauville criteria and International Harmonization Project (IHP) criteria.Methods A total of 212 patients (119 males,93 males,average age:59.6(10-88) years) with DLBCL from February 2010 to June 2018 were analyzed.All subjects underwent restaging PET/CT after treatment.Images were evaluated with the IHP criteria,Deauville score of 3-5 (DC3) and Deauville score of 4-5 (DC4).The diagnostic efficiency of the 3 criteria for treatment effect was assessed and follow-up results were used as the gold standard.Spearman rank correlation analysis was used.Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier analysis and Cox proportional hazards model.Results The positive predictive value and accuracy of DC4 for treatment effect evaluation were 96.8％(61/63) and 94.3％(200/212),those of IHP criteria were 75.3％(67/89) and 87.7％(186/212)respectively,and those of DC3 were 82.9％ (68/82) and 92.0％ (195/212) respectively.IHP criteria results and Deauville scores were correlated(rs =0.926,P＜0.05).The 2-year PFS rates in IHP-,DC3-and CD4-positive groups were 78.7％,76.5％ and 69.8％,respectively,and those in IHP-,DC3-and CD4-negative groups were significantly higher (95.6％,94.7％,97.2％;x2=14.415,18.293 and 26.920,all P＜0.05).The similar results were found for OS rates (x2 =9.597,11.149 and 17.416,all P＜0.05).The 2-year PFS rates in Deauville score of 1,2,3,4,5 groups were 95.3％,91.7％,93.3％,88.9％ and 55.6％ respectively (x2 =48.199,P＜0.05).Cox-regression analysis showed significant correlation between Deauville criteria and 2-year PFS rate (P＜0.05).Conclusions PET/CT with DC4,DC3 and IHP criteria have high predictive values for treatment outcome,and DC4 is the best.Cox regression analysis shows significant risk of progression by Deauville criteria.
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Objective To investigate the characteristics of 18F-Alfatide II PET/CT imaging in normal breasts and breast cancer lesions.Methods From March 2016 to August 2017,22 female patients(age:(52±10)years)with suspected breast malignant nodules or masses were prospectively enrolled.All patients underwent 18F-Alfatide II PET/CT imaging prior to biopsy or surgery.The imaging characteristics of normal breasts were assessed visually and the difference of maximum standardized uptake value(SUVmax)in normal breasts and uterus between patients with and without menopause was compared,SUVmax of cancer lesions and normal breasts was also compared.Breast cancer lesions were classified according to the distribution characteristics of radioactive uptake,and molecular subtypes ware determined by immunohistochemistry and fluorescence in situ hybridization.The SUVmax of different morphological and molecular subtypes were analyzed.Two-sample t test and Pearson or Spearman correlation analysis were used to analyze the data.Results There were 23 breast cancer lesions(one patient had bilateral breast cancer lesions and one had a history of one-side breast resection),20 normal breasts and 21 normal uteruses.Those normal breasts and uteruses didn't show any malignant change after being followed up for more than 1 year(one patient had uterine fibroids resection).There was a slight increase of radioactivity uptake in the cord-like connective tissue region at the margin of the gland in 11 mammary glands,and the SUVmax was higher than that of glandular tissue in the central region(1_81±0.67 vs 0.79±0.37;t = 6.771,P<0.00l).Of the 11 cases,except for one patient whose uterus was removed,the other 10 patients were accompanied by increased diffuse radioactivity of the uterus.SUVmax of 19 normal breast connective tissues(1.31±0.80)and uterus(3.80+1.79)were positively correlated(r = 0.785,P<0.05).For patients with/without menopause(n= 11 each group),the SUVmax of normal breast connective tissues(0.72±0.39 vs 1.81±0.67)and uterus(2.04±0.39 vs 5.11 + 1.06)were significantly different(t values:4.42 and 8.66,both P<0.01).Different levels of radioactive uptake were observed in all 23 breast cancer lesions,with SUVmax of 6.93±3.97,which was significantly higher than the nipple,connective tissue and glandular tissue of normal breasts(t values:6.784-7.559,all P<0.05).According to the characteristics of the radioactivity uptake distribution of the lesion,among the 23 breast cancer lesions,5 were mass type,3 were nodular type,4 were diffuse type,and 11 were multi-focal/multi-center type,and the SUVmax of multi-focal/multi-center type was the highest(F=3.55,P<0.05).The SUVmax of basal-like breast cancer lesions(2.49±1.67)was lower than the other three molecular subtypes.Lesions with high level human epidermal growth factor receptor 2(HER2)positive expression had higher SUVmax.Conclusions 18F-Alfatide II PET/CT imaging shows that normal breasts have a slight radioactive distribution,mainly concentrate in the nipple and connective tissues around the glandular,and the uptake have a positive correlation with the radioactive uptake of the uterus.The degree of radioactive uptake of breast cancer lesions is significantly higher than that of normal breasts.Breast cancer lesions with different moqjhological features all have obvious radioactive uptake,especially the multi-focal/multi-center type.Different molecular subtypes have different radioactive uptake levels.SUVmax is lower in basal-like breast cancer lesions,and higher in HER2 positive expression lesions.
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Objective To analyze the image characteristics and clinical value of 18F-FDG PET/CT in patients with extranodal nasal type natural killer/T-cell lymphoma (ENKTL).Methods From January 2012 to March 2016,20 ENKTL patients (12 males,8 females;median age 53 years) who underwent whole-body 18F-FDG PET/CT were enrolled in this retrospective study.Eleven patients were newly diagnosed,and 9 were previously treated.Clinical data were collected for histopathology and bone marrow biopsy,laboratory results,PET/CT and radiological findings such as CT or MRI.The final diagnosis was based on histopathology and immunohistochemistry.Mann-Whitney u test was used to compare the SUVmax of newly diagnosed patients and patients with recurrence or disease progression after therapy.Spearman correlation analysis was used to explore the relation between diameter of tumor-invaded lymph nodes and SUVmax.Results ENKTL could be found in all parts of the body,but more frequently in the nasal cavity,nasopharynx and skin.All lesions showed high uptake of FDG on PET/CT.The SUVmax of newly diagnosed patients was significantly higher than that of patients (n=7) with recurrence or disease progression:6.5(4.3,10.4) vs 5.4(3.4,8.9);u=6 853.500,z=-2.039,P＜0.05).The diameter of tumor-invaded lymph nodes showed weakly positive correlation with SUVmax(rs =0.290,P＜0.01),suggesting that invasion of ENKTL might not be accurately evaluated by the size of lymph nodes.The staging by PET/CT was concordant with clinical final staging in 11 newly diagnosed patients,while the staging by CT or MRI was only correct in 6 patients.Conclusions PET/CT is superior to conventional imaging modalities in diagnosis and staging for patients with ENKTL.Since some lesions might be found in the limbs,limbs should be included in the scan field.
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Objective To analyze the relevant factors influencing 18F-FDG uptake in the primary lesion of breast invasive ductal carcinoma (BIDC).Methods A total of 160 female patients underwent 18 F-FDG PET/CT examination from 2010 to 2015 and breast lesions were revealed.Lesions were divided into benign group (n =118) and malignant group (n =49,BIDC) according to pathological results.KruskalWallis H test and Mann-Whitney u test were performed to compare SUVmax of the two groups,and to investigate the relationship between the SUVmax of breast malignant lesion and patients' age as well as clinical pathological parameters including T stage,lymphatic vessel invasion,nuclear grade,route of metastasis,ER,PR,HER2 and Ki-67 expression,and subtype of breast cancer.The diagnostic efficiency of 18F-FDG PET/ CT in differentiating benign and malignant breast lesions was analyzed using ROC curve analysis.Results The SUVmax of BIDC was 6.09(3.88,9.26),higher than that of breast benign lesion (1.35 (0.95,2.35);u=341.0,P＜0.05).The SUVmax of BIDC showed statistically significant difference between groups with different T stage,with or without lymphatic vessel invasion,with different nuclear grade,different routes of metastasis and different Ki-67 expression (u:117.5-209.5,H=7.70,P＜0.01 or 0.05).For all breast lesions,lesions with the maximum diameter ≤ 2.0 cm and lesions with the maximum diameter ＞2.0 cm,the optimum cutoff values of SUVmax were ＞2.60,＞ 1.71 and ＞3.97,respectively.When the optimum cutoff values of SUVmax for breast lesions with the maximum diameter ≤2.0 cm were selected as ＞ 1.71 and ＞2.60,the Youden indexes were 0.66 and 0.61(z=0.566,P＞0.05).When the optimum cutoff values of SUVmax for breast lesions with the maximum diamter ＞2.0 cm were selected as ＞3.97 and ＞2.60,the Youden indexes were 0.89 and 0.81(z=0.748,P＞0.05).Conclusions T stage,lymphatic vessel invasion,nuclear grade,route of metastasis and Ki-67 expression of BIDC influence the uptake of 18F-FDG by tumor tissues.The SUVmax of the primary lesion of BIDC is related to the size of lesion,and thus the diagnostic threshold of SUVmax should be decreased appropriately for small lesions.
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Objective To evaluate the relationship between 18F-FDG uptake and P-gp expression in Bcap37 or Bcap37/MDR1 tumor-bearing BALB/c nude mice.Methods Bcap37 or Bcap37/MDR1 cells were injected into BALB/c nude mice (1× 107cells/ml,0.2 ml/mouse) to construct mice models.Bcap37 (n=5) or Bcap37/MDR1 (n=5) tumor-bearing mice fasted for 6 h before imaging.After anesthesia,the mice were injected with 7.4 MBq of 18F-FDG via tail vein.The dynamic microPET scans were carried out for 90 min.On the microPET images,the ROI was drawn and the TAC was obtained.The next day,those 10 mice underwent dynamic microPET scans after injected with elacridar (GF120918) and 18F-FDG.Another 10 mice,5 with Bcap37 tumors and 5 with Bcap37/MDR1 tumors,were used.After 7.4 MBq 18F-FDG with or without 2.0 mg/kg GF120918 was administered via tail vein,microPET images were acquired at 60 min.ROI was drawn over the tumors and SUV was obtained.Two-sample t test was used to analyze the data.Results GF120918 did not significantly alter the 18F-FDG accumulation curve in Bcap37 tumors,but significantly enhanced the 18F-FDG accumulation in Bcap37/MDR1 tumors.GF120918 did not influence 18F-FDG uptake (SUV) in Bcap37 tumors (1.052±0.028,1.028±0.045,t =1.792,P＞0.05),but significantly increased the SUV in Bcap37/MDR1 tumors (1.015±0.043,0.712±0.031,t=3.365,P＜0.05);The SUV of 18 F-FDG in Bcap37 tumors was significantly higher than that in Bcap37/MDR1 tumors without injection of GF120918 (t =3.952,P＜0.05).The SUV was not significantly different when GF120118 was injected (t=1.835,P＞0.05).Conclusions 18F-FDG is a substrate of P-gp.18F-FDG imaging combined with GF120918 injection may be an effective noninvasive method for the detection of tumor's MDR.
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Objective To evaluate the value of whole body 18F-FDG PET/CT in the detection of recurrence/metastasis of cervical cancer.Methods A retrospective study was performed on 95 patients with cervical cancer who underwent 18F-FDG PET/CT after treatment.The lesion characteristics on 18F-FDG PET/CT were assessed visually and semi-quantitatively.A final diagnosis was confirmed by histopathology,diagnostic treatment and clinical follow-up imaging.The data were analyzed by Kappa test.Results 18 F-FDG PET/CT was positive in 54 patients,including 24 with local recurrence and 30 with distant metastases.The sensitivity,specificity and accuracy of 18F-FDG PET/CT for the detection of recurrence/metastasis of cervical cancer were 98.1％ (52/53),95.2％ (40/42) and 96.8％ (92/95),respectively.The positive predictive and negative predictive value were 96.3％ (52/54) and 97.6％ (40/41),respectively.18F-FDG PET/CT showed concordant results with pathological/clinical follow-up findings (Kappa =0.936,P＜0.05).Conclusion 18F-FDG PET/CT is a sensitive and specific modality for the detection of recurrence/metastasis of cervical cancer and might be useful for further treatment plan.
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Objective To investigate the value of gastrointestinal tract preparation with oral racean?isodamine tablets and isotonic mannitol in 18 F?FDG PET/CT imaging. Methods From July to September 2013, 129 patients with confirmed or suspected tumors who were referred for 18 F?FDG PET/CT imaging were divided into 2 groups. In the study group (30 males, 37 females, age (53.4±13.9) years), raceanisodam?ine tablets (10 mg) and 1 000-1 200 ml isotonic mannitol solution (2.5%) were orally taken at 10 min after in?jection of 18F?FDG;while in the control group (37 males, 25 females, age (60.0±12.8) years), 1 000-1 200 ml water was given. Mann?Whitney u test was used to compare the difference between the 2 groups in the filling degree of gastrointestinal lumen, delineation of tube wall, physiological uptake, matching degree of PET and CT images, delineation of mesentery, and the influence of gastrointestinal uptake on the identification of ab?dominal and pelvic lesions. χ2 test was used to compare the difference between the 2 groups in the uptake pattern of gastrointestinal tract and the incidence of side effects. Spearman correlation analysis was used to study the correlation between gastrointestinal lumen filling and PET/CT image matching. Results The gas?trointestinal lumen filling, delineation of tube wall, PET/CT image matching in the stomach, small intestine and colon (z: -5.096 to -2.665, all P0.05). There was statistically significant difference in the uptake pattern of small intestine between the two groups(χ2=12.884, P0.05). The incidence of transient diarrhea (20?9%, 14/67) was higher in the study group than that in the control group (4.8%, 3/62;χ2=7.256,P<0.01). Conclusions The abdominal PET/CT image quality is improved by gastrointestinal preparation with oral raceanisodamine tablets (10 mg) and 1 000-1 200 ml isoton?ic mannitol solution (2.5%).
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Objective To evaluate the effect of P-gp inhibitors of verapamil (VER) and GF120918 on 18F-FDG uptake in Bcap37 and Bcap37/multidrug resistancce (MDR)1 cell lines in vitro,and to explore the relationship between 18F-FDG uptake and P-gp expression at cellular level.Methods Bcap37 and Bcap37/MDR1 cells were seeded into 6-well plates at a density of 1 × 106 per well.Three days later,37 kBq/ml 18F-FDG,or 37 kBq/ml 18F-FDG + 100 μmoL/L VER,or 37 kBq/ml 18F-FDG + 50 μmol/L GF120918 were added into each well.Mter incubated for 10,30,60 and 120 min at 37 ℃ and in 5％ CO2,the medium was removed and the cells were washed three times with 1 ml ice-cold PBS immediately.The radioactivity of 18 F-FDG was measured using a gamma counter.The uptake of 18F-FDG was expressed as the ratio of 18F-FDG radioactivity in Bcap37 or Bcap37/MDR1 cells and the overall radioactivity added to the cells in each well.The t test was used for statistical analysis.Results 18F-FDG uptake was higher in Bcap37/MDR1 cells than that in Bcap37 cells after incubated for 10 min.The uptake rate was (1.88 ±0.19) ％ in Bcap37/MDR1 cells and (1.37 ± 0.18) ％ in Bcap37 cells (t =7.832,P ＜ 0.05).On the contrary,18 F-FDG uptake was significantly higher in Bcap37 cells than that in Bcap37/MDR1 cells after incubated for 60 and 120 min.The uptake rates were (2.29 ±0.23)％ and (2.34 ±0.15)％ in Bcap37 cells,(1.47 ±0.14)％ and (1.53 ±0.22)％ in Bcap37/MDR1 cells (t =8.437,8.283,both P ＜ 0.05).18 F-FDG uptake was significantly higher with VER or GF120918 in Bcap37/MDR1 cells than that without VER or GF120918 after the incubation of 60 and 120 min (t =9.032,9.243 and 8.765,8.803,all P ＜ 0.05).The uptake rates with VER or GF120918 were (2.45 ±0.21)％ and (2.46 ±0.25)％,(2.50 ±0.24)％ and (2.48 ±0.27)％.There was no significant difference of 18F-FDG uptake in Bcap37 cells with or without VER or GF120918.Conclusions 18F-FDG is a substrate of P-gp at cellular level.P-gp may act as an efflux pump to reduce 18F-FDG uptake in Bcap37/MDR1 cells.The uptake of 18F-FDG can be used to evaluate the function of P-gp in tumor cells.