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Automatic synthesis of N-succinimidyl 4-18F-fluorobenzoate and its utility for 18F labeled C2A donain of synaptotagmin I

Yan-jie, HOU ; Biao, LIU ; Zi-zheng, WANG ; Xu-dang, XU ; Shao-hua, LI ; Wei, TIAN ; Feng, WANG

Chinese Journal of Nuclear Medicine.2010;30(6):414-418. doi:10.3760/cma.j.issn.0253-9780.2010.06.015

Objective To develop and optimize a module for the automatic production of N-succinimidyl-4-[18F] fluorobenzoate (18F-SFB) that is used for further 18F labelling C2A domain of Synaptotagmin Ⅰ . The conjugated compound was applied for detecting the tumor apoptosis in rabbit model after chemotherapy. Methods GE TRACERlab and TRACERlab FXF-N modules were modified and programmed to automatically produce 18 F-SFB which was further analyzed by high performance liquid chromatography (HPLC).C2A-glutathione S transferase (GST) was conjugated with 18F-SFB (18F-FB-C2A-GST) and subsequently purified by HPLC. Two rabbits grafted with VX2 lung cancer were first treated with chemotherapy and then,37 MBq of 18F-FB-C2A-GST was administered via the auricular vein. Serial PET/CT imagings were performed at 0.5, 1 and 2 h post-injection respectively. Tumor apoptosis was examined by pathological study. Results The TRACERlab FXFoG and TRACERlab FXF-N modules were successfully adapted to synthesize18F-SFB, with the radiochenmical yield (76.41 ±4.00)% (n = 10), the corrected yield (45.43 ±5.90 ) % and the radiochemical purity about 95%. The whole procedure for labeling 18 F-SFB was about 87 min.From PET/CT imagings, significant uptake was found in the tumor after chemotherapy, but no obvious up-take was found in heart, lungs and liver. HE staining demonstrated large number of apoptotic bodies within the tumor tissues. Conclusions 18 F-SFB can be automatically synthesized. 18F-FB-C2A-GST might be useful for the detection of apoptosis in tumor after chemotherapy.

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Preparation of 131I-K237 and the experimental study on targeting therapy in nude mice bearing human lung cancer

Huo-qiang, WANG ; Jun-yong, XIA ; Zhi-yong, ZHANG ; Long, ZHAO ; Jin-xu, ZHENG

Chinese Journal of Nuclear Medicine.2010;30(6):390-394. doi:10.3760/cma.j.issn.0253-9780.2010.06.010

Objective To establish the radiolabeling method for peptide K237 with 131I and investigate the biodistribution and therapeutic efficacy of 131I-K237 on nude mice bearing human lung cancer.Methods Iodogen method was used for labeling K237. The bioactivity of 131I-K237 was tested by human umbilical vein endothelial cell ( HUVEC ) proliferation inhibitory assay and the affinity of 131I-K237 was examined by competition binding studies. Twenty-five mice were divided into five groups randomly, including physiologic saline (group 1), K237 (40 μg) (group 2), 131I ( 11. 1 MBq) (group 3), 131I-K237 (K237 40 μg, 11. 1 MBq) intravenously ( group 4), and 131I-K237 ( K237 40 μg, 11.1 MBq) intratumorally (group 5). Injections were repeated at 15 d after the first injection. The tumor growth inhibition rate was calculated. Student's t-test and analysis of variance (ANOVA) were used for testing significant differences of data. Results The inhibition rate of HUVEC proliferation had no significant difference between radiolabeled K237 and unlabeled K237 ( (73.69 ± 5.36) % vs ( 62.68 ± 3.83 ) %, t = 1.67, P ＞ 0.05 ). The growth of transplanted lung cancer was inhibited by 75. 01 % in group 4, 78.99% in group 5, 31.15% in group 2 and 12.61% in group 3, respectively. The average tumor volume of groups 4 and 5 were significantly smaller than that of groups 1,2, and 3 ( F = 15. 233 and 13.611, respectively, P ＜0. 01 ). Conclusion 131I-K237 can be readily radiolabeled and it can effectively inhibit the growth of tumor in nude mice bearing human lung cancer.

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The study of ictal brain SPECT during seizures induced by clonidine and sleep-deprivation in patients with epilepsy

Xiao-hui, WANG ; Xue-hong, CHEN ; Zheng-jiang, WANG ; Jiang-yan, LIU ; Jian-zhong, FENG ; Jiang, YE ; Li, ZHAO

Chinese Journal of Nuclear Medicine.2010;30(6):375-378. doi:10.3760/cma.j.issn.0253-9780.2010.06.006

Objective To evaluate the feasibility and clinical value of combined clonidine and sleep-deprivation induced seizures for ictal brain SPECT imaging in patients with epilepsy. Methods Fiftytwo epilepsy patients were given oral clonidine plus sleep-deprivation to induce seizures with video-electroencephalogram (VEEG) monitoring. Forty-seven patients were selected as control group, whose seizures were induced by sleep-deprivation only. 99Tcm-ethylcysteinate dimer (ECD) was injected within 30 s since a clinical sign and/or a typical EEG discharge of epilepsy was recognized. Brain SPECT was performed 30 min after 99TcmECD injection. X2-test was performed by using software SPSS 10. 0. Results One to two hrs after oral intake of clonidine plus sleep-deprivation, 75% (39/52) patients were induced seizures, including 92.3% (36/39) with subclinical seizures and 7.7% (3/39) with clinical seizures. Ictal brain SPECT localized the lesions with high uptake of 99Tcm-ECD in 37 (94.9%) patients. In control group, 38.3% ( 18/47) were induced epileptic seizures, including 77.8% (14/18) with subclinical seizures and 22.2% (4/18) with clinical seizures. The induction rate of epileptic seizures in clonidine plus sleep-deprivation group was significantly higher than that of control group (X2 = 13.614, P ＜ 0.01 ). However, there was no significant difference in clinical seizures between the two groups (X2 = 1.253, P ＞ 0.05 ). Conclusions The combination of oral intake of clonidine and sleep-deprivation could increase the induction rate of epileptic seizures and it is effective for epilepsy SPECT imaging.

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Comparative study of myocardial perfusion imaging and 64 multi-slice spiral CT for the diagnosis of coronary artery disease

Jun, ZHAO ; Long-bao, XU ; Ren-ming, WAN ; Guang-lei, FAN ; Jian-wen, LIU ; Shu-xing, HUANG

Chinese Journal of Nuclear Medicine.2010;30(6):367-371. doi:10.3760/cma.j.issn.0253-9780.2010.06.004

Objective To compare the diagnostic value of myocardial perfusion imaging (MPI) and 64 multi-slice spiral CT (64-MSCT) for coronary artery disease (CAD). Methods Fifty-two patients with suspected or known CAD were included in the study. Each patient underwent both stress and rest MPI,MSCT as well as conventional coronary angiography (CAG) within 1 month. The stress and rest MPI were scored by a 5-grade criteria (0 ～ 4) based on 17 coronary artery segments. The difference between summed stress and rest scores ＞ 1 was defined as myocardial ischemia. Stenosis in one main vessel or one main branch of the main vessel ≥50% was defined as myocardial ischemia by MSCT. CAG was used as the reference for comparison. Statistical analysis was performed using SPSS 13. 0 software. Kappa value was used to test the accordance of MPI and MSCT results. X2 test was used to evaluate the difference between MPI and MSCT results. Results The patient-based sensitivity, specificity, positive and negative predictive values and accuracy of MPI and MSCT for the diagnosis of CAD were 86.7% (26/30), 77.3% ( 17/22),83.9% (26/31), 81.0% ( 17/21), 82.7% (43/52) and 83.3% ( 25/30), 86.4% ( 19/22), 89.3%( 25/28), 79.2% ( 19/24), 84.6% (44/52), respectively. The vessel-based sensitivity, specificity, positive and negative predictive values and accuracy of MPI and MSCT were 74.5% (38/51), 81.0% (85/105 ), 65.5% (38/58), 86.7% ( 85/98), 78.8% ( 123/156 ) and 90.2% (46/51 ), 88.6% ( 93/105 ),79.3 % (46/58), 94.9% (93/98), 89.1% ( 139/156), respectively. There was no statistically significant difference between MPI and MSCT for either patient or lesion-based diagnosis (X2 =0.44, 0.21, both P ＞0.05 ). 96.0% (24/25) patients with both abnormal MPI and MSCT positive were valified by CAG while 83.3% (15/18) patients with both MPI and MSCT negative were excluded by CAG. Conclusions Both MPI and MSCT are reliable diagnostic modalities for CAD. They also provide complementary diagnostic value to each other.

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Evaluation of myocardial blood supply using adenosine stress myocardial perfusion imaging

Qian, WANG ; Ji-min, YANG ; Hong-zhi, MI ; Fang, GUO ; Jian, JIAO ; Jing-jing, MENG ; Jian, DING ; Yao, LU

Chinese Journal of Nuclear Medicine.2010;30(6):363-366. doi:10.3760/cma.j.issn.0253-9780.2010.06.003

Objective To retrospectively evalute the value and accuracy of adenosine stress and rest SPECT myocardial perfusion imaging. Methods A total of 1858 patients who were suspected or known for coronary artery disease (CAD) underwent 99Tcm-methoxyisobutylisonitrile ( MIBI ) myocardial perfusionSPECT with adenosine infusion using the standard 2-day protocol. Images were interpreted by two or more experienced nuclear medicine physicians . Coronary angiography was carried out in all patients within one month. Kappa test was used to analyze the correlation between the two imaging studies. Results By coronary angiography, there were 957 patients diagnosed of CAD (one-, two-, three-vessel disease: 506,256,195, respectively) and 901 normal. Stenosis was found in 1603 vessels, including left anterior descending coronary artery (LAD): 765, left circumflex coronary artery (LCX): 399 and right coronary artery (RCA): 439. By adenosine induced stress myocardial perfusion imaging, 876 patients were diagnosed of myocardial ischemia ( sensitivity: 876/957, 91.54% ) and 651 patients had negative findings ( specificity:651/901,72.25 % ). The positive and negative predictive values were 77.80% ( 876/1126 ) and 88.93% (651/732), respectively. The correlation coefficient between the two imaging studies was 0.641. The vessel-based sensitivity was 81.31% (622/765) for LAD, 56.64% (226/399) for LCX and 70.62% (310/439) for RCA, respectively. The sensitivity for detection of one-, two-, three-vessel stenosis was 87.55% (443/506), 94.92% (243/256) and 97.44% (190/195), respectively. The side-effects was mild and transient with an incidence rate of 84.12% ( 1563/1858), without major cardiac events. Conclusion Stress myocardial perfusion imaging induced by adenosine is reliable for the evaluation of myocardial blood supply in CAD patients.

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A phantom study of tumor contouring on PET imaging

Song, CHEN ; Xue-na, LI ; Ya-ming, LI ; Ya-fu, YIN ; Na, LI ; Chun-qi, HAN

Chinese Journal of Nuclear Medicine.2010;30(6):419-423. doi:10.3760/cma.j.issn.0253-9780.2010.06.016

Objective To explore an algorithm to define the threshold value for tumor contouring on 18F-fluorodexyglucose (FDG) PET imaging. Methods A National Electrical Manufacturing Association (NEMA)NU 2 1994 PET phantom with 5 spheres of different diameters were filled with 18F-FDG. Seven different sphere-to-background ratios were obtained and the phantom was scanned by Discovery LS 4. For each sphere-to-background ratio, the maximum standardized uptake value ( SUVmax ) of each sphere, the SUV of the border of each sphere ( SUVborder ), the mean SUV of a 1 cm region of background (SUVbg) and the diameter (D) of each sphere were measured. SPSS 13.0 software was used for curve fitting and regression analysis to obtain the threshold algorithm. The calculated thresholds were applied to delineate 29 pathologically confirmed lung cancer lesions on PET images and the obtained volumes were compared with the volumes contoured on CT images in lung window. Results The algorithm for defining contour threshold is TH% = 33.1% + 46.8% SUVbg/SUVmax + 13.9%/D ( r = 0.994) by phantom studies. For 29 lung cancer lesions, the average gross tumor volumes ( GTV ) delineated on PET and CT are ( 7.36 ± 1.62 ) ml and (8.31 ±2.05) ml, respectively (t = -1.26, P＞0.05). Conclusion The proposed threshold algorithm for tumor contouring on PET image could provide comparable GTV with CT.

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Research on multifunctional 18F synthesis module with two vessels

Jin-ming, ZHANG ; Xiao-jun, ZHANG ; Yun-gang, LI ; Jian, LIU ; Sheng-min, YU ; Jia-he, TIAN

Chinese Journal of Nuclear Medicine.2010;30(6):410-413. doi:10.3760/cma.j.issn.0253-9780.2010.06.014

Objective To explore a new 18F multifunctional synthesis module with two vessels to synthesize various kinds of 18F labeled radiopharmaceuticals for clinical utilities. Methods The module with two vessels contained five systems, capture of F ion, the first reaction vessel, the second reaction vessel, high performance liquid chromatography (HPLC) purification, and solid extraction. The two vessels were made of transparent glass and were used to prepare complex products by nucleophilic reaction or hydrolyzation. Results The complex compounds of 18F-ethyl-choline, 18F-N-succinimidyl-4-18 F-fluorobenzoate (SFB), and common compounds of 18F-fluorodeoxyglucose (FDG), 18F-3'-deoxy-3'-18 F-fluorothymidine (FLT) were synthesized by the new module. The uncorrected synthesis yield (EOS) of 18F-SFB, 18F-ethylcholine, and 18F-FDG were (28.2±1.9)% (n=5), (22.5±3.8)%(n=6), and (58.2±5.4)% (n=32), respectively. The corrected synthesis yield of 18F-FLT was (30.1 ±6.2)% ( n = 10). In addition,11C-N-methyl-N-( 1-methylpropyl )-1-( 2-corophenyl )-isoquinoline-3 -carboxamide ( PK11195 ) was also prepared by the module with the yield of (31.2 ± 2.5) % ( n = 3 ). Conclusions The new module with two vessels has been used for synthesis of many 18F compounds and it may have the potential to be used for other more 18F radiopharmaceuticals.

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125I uptake in U251 glioma cell co-transfected with the human sodium/iodide symporter and the human thyroperoxidase

Bei, WU ; Jian, TAN ; Lei, LONG ; Wei, LI

Chinese Journal of Nuclear Medicine.2010;30(6):395-399. doi:10.3760/cma.j.issn.0253-9780.2010.06.011

Objective To investigate the iodide uptake by U251 glioma cell lines which were transfered with both human sodium/iodide symporter (hNIS) and human thyroperoxidase (hTPO) genes. Methods Recombinant adenosine virus AdTPO was constructed through cloning, recombination, packaging and amplifying. The viral titers were calculated after purification. The protein expression of AdTPO was tested by Western-Blotting and the recombinant plasmids PcDNA3. 1/hNIS were constructed. After hNIS gene was transfected into human glioma cell lines U251 through liposome, the cell lines with stable hNIS expression (hNIS-U251) selected by G418 antibiotics were defined as hNIS-U251 group. Then, hTPO was transducted into hNIS-U251 with adenosine virus (AdTPO-hNIS-U251 group). U251 cells with no plasmid were used as the control group (U251). Cultured cells from each group were studied for 125I uptake as well as 125I efflux rate. Student-Newman-Keuls in multiple range test was used. Results AdTPO-hNIS-U2.51 with stable expression was successfully established by transfecting hNIS and hTPO genes into human glioma cell lines. The 125I uptake by AdTPO-hNIS-U251, hNIS-U251 and U251 cell lines was (74 647.53 ±3605.88), (55 769.96 ±4353.26) and ( 507.67 ± 57.69 ) counts/min, respectively ( F = 836. 17, P ＜ 0.05 ). The uptake compacity by AdTPO-hNIS-U251 was 147 fold higher than that by U251 (q =55.64, P＜0.01 ) and 1.3 fold higher that by hNIS-U251 (q = 14. 17, P ＜0.01 ). 125I efflux rate was prolonged in AdTPO-hNIS-U251 group and its effective half time was 13 min. Conclusion Enhanced 125I uptake by the human glioma cell lines can be achieved with combined transfection of hNIS and hTPO genes.

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Predictive value of ventilation and perfusion scintigraphy for the postoperative pulmonary function in patients with lung cancer

Xiao-hua, ZHU ; Ming, ZHAO ; Chuan, LIU ; Jian, ZHOU ; Dan, ZHU

Chinese Journal of Nuclear Medicine.2010;30(6):387-389. doi:10.3760/cma.j.issn.0253-9780.2010.06.009

Objective To evaluate the value of ventilation and perfusion scintigraphy for predicting the postoperative pulmonary function in patients with lung cancer. Methods Twenty-six patients with lung cancer, male 21 and female 5, aged from 44 to 86 ys, were recruited into the study. Before surgery, 21 patients underwent 99Tcm-DTPA aerosol ventilation and 99Tcm-macroaggregated albumin ( MAA ) perfusion scintigraphic imaging. The other five patients were studied with perfusion imaging only. Pulmonary function was measured as forced expiratory volume in the first second ( FEV1 ) at about one week before surgery for all patients, and at two months after surgery. The predicted postoperative FEV1 ( ppoFEVt ) was calculated by Neuhaus' formula based on the ventilation or perfusion function obtained from scintigraphy studies, and compared with the measured post surgery FEV1. Eighteen patients underwent the surgical resection successfully. The t-test and correlation analysis were used. Results The ppoFEV1 values of ventilation and perfusion were (1.347±0.539) Land (1.410±0.543) L, respectively (n=21, t =0.062, P＞0. 05). Both the ppoFEV1 values of ventilation and perfusion showed no significant difference with the respective post-surgeryFEV1(n=13, (1.545 ±0.588) Lvs (1.45 ±0.521) L, t=0.092, P＞0.05; n=18, (1.697±0. 546) L vs ( 1.457±0.488) L, t =0. 017, P ＞0.05, respectively). Both the ventilation ppoFEV1 (n =13) and perfusion ppoFEV1 (n = 13, n = 18) correlated well with the post-surgery FEV1 respectively (r =0. 950, 0. 937, 0. 922, all P ＜ 0. 01 ). Conclusion Ventilation and perfusion imaging can predict the postoperative pulmonary function for patients with lung cancer, especially for those with borderline pulmonary function, thus useful for selection of suitable candidates for surgical resection.

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Comparison of 18F-FLT and 18F-FDG PET/CT for lymph node staging in thoracic esophageal carcinoma

Da-li, HAN ; Xiao-jun, ZHONG ; Jin-ming, YU ; Dian-bin, MU ; Zheng, FU ; Bai-jiang, ZHANG ; Li-min, ZHANG ; Wei-di, ZHANG ; Shu-guang, LIU ; Shu-qiang, ZHAO ; Xiao-hui, WANG ; Fang, YUAN ; Hong-ai, WANG

Chinese Journal of Nuclear Medicine.2010;30(6):383-386. doi:10.3760/cma.j.issn.0253-9780.2010.06.008

Objective To compare the diagnostic value 18F-fluorothymidine (FLT) and 18F-fluorodeoxyglucose (FDG) PET/CT in detecting lymph node metastases of untreated thoracic esophageal carcinoma. Methods Twenty-two patients with thoracic esophageal squamous cell carcinoma underwent both 18F-FLT and 18F-FDG PET/CT before surgery. The imaging results of the two modalities in detecting regional lymph node metastases were compared prospectively with the pathologic findings. The X2-test was used with SPS S 13.0. Results All patients underwent esophagectomy and lymphadenectomy. The metastatic lymph nodes were found in 16 patients, from which 47 of 424 excised nodes were positive by pathologic examination. False positive results were 14 while false negative 8 on 18F-FDG PET/CT. In contrast, false positive results were only 3 but false negative were 12 on 18 F-FLT PET/CT. The sensitivity, specificity, accuracy,negative predictive value, and positive predictive value were 74.47% ( 35/47 ), 99.20% ( 374/377 ),96.46% (409/424), 96.89% ( 374/386 ) and 92.11% ( 35/38 ) respectively for 18 F-FLT PET/CT, whereas the corresponding values were 82.98% (39/47), 96.29% (363/377), 94.81% (402/424), 97.84%(363/371 ) and 73.58% (39/53) respectively for 18 F-FDG PET/CT (X2 = 0.572, 6.018, 1.017, 0.348,3.852, P＞0. 05, ＜0.05, ＞0.05, ＞0.05 and ＞0.05). Conclusions Compared with 18F-FDG PET/CT, 18F-FLT PET/CT may be less sensitive but more specific for the detection of lymph node metastases of thoracic esophageal carcinoma.

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