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Objective:To investigate the effects of different labeling conditions on the yield of Al 18F-labeled 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA)-prostate specific membrane antigen (PSMA)-137, and to determine the experimental condition for obtaining Al 18F-PSMA-137 probe in high yield. Methods:The effects of different pH values, buffer systems (acetic acid-sodium acetate buffer system and potassium hydrogen phthalate (KHP) buffer system), AlCl 3-ligand ratios, ligand amounts, ethanol volumes and reaction temperatures on the labeling rate were investigated in detail. Results:The pH value of the reaction solution had a significant effect on the labeling rate, and the optimal range was 4.0-4.5. When the pH value was higher than 4.5, the labeling rate decreased significantly. Both the acetic acid-sodium acetate buffer system and the KHP buffer system could be used to label NOTA-PSMA-137 with Al 18F, and the KHP buffer system obtained higher labeling rate. The ratio of AlCl 3-ligand affected the labeling rate, and the highest labeling rate could be obtained when the ratio of AlCl 3-ligand was 0.54-0.62. When the ratio of AlCl 3-ligand was fixed, increasing the amount of ligand could improve the labeling yield. Adding hydrophilic organic solvent ethanol to the reaction system could significantly increase yield, with the highest labeling rate being achieved at a volume of 100 μl ethanol. The most suitable reaction temperature was 100 ℃, and when the temperature raised to 110 ℃, the labeling rate decreased significantly. The most suitable labeling conditions for NOTA-PSMA-137 were as following: 25 μl KHP buffer (0.50 mol/L, pH=4.0), 7.0 μl AlCl 3 solution (20 mmol/L), 200 μl Na 18F solution (74-80 MBq) and 230 μg ligand NOTA-PSMA-137 were mixed in a vial, then stood for 5 min and 100 μl ethanol was added, and all reagents were heated at 100 ℃ for 10 min. The yield of Al 18F-PSMA-137 under above conditions were 85.7%-88.5%. Conclusion:Optimization of labeling condition can improve the yield of Al 18F-PSMA-137 and the stability of the labeling.
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Objective:To prepare a novel targeted prostate specific membrane antigen (PSMA) molecular probe Al 18F-PSMA-136, and evaluate the effects of the change in linker on the biological behavior and tumor targeting ability. Methods:Al 18F-PSMA-136 was prepared by replacing the phenyl of Al 18F-PSMA-137 with cyclohexyl in 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA). The inhibition abilities of PSMA of NOTA-PSMA-136 and NOTA-PSMA-137 were determined by N-acetylated-α-linked acidic dipeptidase (NAALADase) method. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio-high-performance liquid chromatography. The PSMA specificity and tumor targeting capability of the probes were investigated in 22Rv1 (PSMA positive-expressing) cells and mouse models. Independent-sample t test was used to analyze the data. Results:The Ki values of NOTA-PSMA-136 and NOTA-PSMA-137 were 3.41 and 0.30 nmol/L, respectively. The labeling yield of Al 18F-PSMA-136 was (30.1±8.4)% and the specific activity was (18.7±5.3) GBq/μmol. The radiochemical purities of the two probes were both greater than 95% and the stabilities in vitro were both good. Both probes showed PSMA-specific in 22Rv1 cells, but the uptake of Al 18F-PSMA-137 was significantly higher than that of Al 18F-PSMA-136 (1 h: (1.67±0.24) vs (1.00±0.01) percentage injected activity per 1×10 5 cells (%IA/1×10 5 cells): t=4.78, P=0.003; 2 h: (2.11±0.06) vs (1.03±0.06) %IA/1×10 5 cells; t=19.90, P<0.001). MicroPET/CT imaging showed that Al 18F-PSMA-136 and Al 18F-PSMA-137 had similar distribution in vivo, mainly concentrated in kidneys, intestine, gallbladder, bladder and tumor. However, the uptake of Al 18F-PSMA-137 in tumor was significantly higher than that of Al 18F-PSMA-136 (1 h: 1.78±0.10 vs 0.54±0.08; t=13.29, P<0.001; 2 h: 1.95±0.01 vs 0.52±0.11; t=18.53, P<0.001). Conclusion:Changes in the NOTA-conjugated linker can significantly affect the PSMA inhibition ability and tumor targeting, and the imaging effect of Al 18F-PSMA-137 with strong lipophilicity is superior.
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The application of isotope exchange can realize radiolabeling in partially aqueous media, proceed under mild reaction conditions, and exclude complex purification procedure. It is suitable for one-step labeling of sensitive biomolecules with clinical application potential. This review systematically introduces the 18F/ 19F isotope exchange reactions based on carbon and those non-carbon-based reaction centers including silicon, boron, phosphorus, sulfur, gallium and iron. Discussions of the effects on isotope exchange radiochemical yields and molar activities by different reaction types, and labeling conditions and substitute groups on classic labeled substrate are held where possible, as well as recent applications in using these methodologies to develop PET probes.
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Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.
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Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.
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Objective:To explore the automatic synthesis method of 18F-AlF-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-octreotide and the imaging in neuroendocrine tumor (NET). Methods:Using the Trasis AllinOne synthesis module, 18F-AlF-NOTA-octreotide was automatically synthesized by chelating 18F-AlF and NOTA-octreotide at 100 ℃, and the quality of the product was analyzed. 18F-AlF-NOTA-octreotide and 18F-FDG PET/CT imaging were performed and compared in one patient with NET (male, 35 years old). Results:The total synthesis time of 18F-AlF-NOTA-octreotide was 35 min with a radiochemical yield of (55.8±1.8%)% (non-decay corrected, n=6), radiochemical purity more than 95% and good stability. The sterility and pyrogen-free of the product met the requirements. Compared with 18F-FDG (the lesion SUV max=3.8, target-to-background (T/B) ratio=1.03), 18F-AlF-NOTA-octreotide could be clearly imaged in the patient with NET with SUV max of 21.7 and T/B ratio of 4.09. Conclusions:The preparation of 18F-AlF-NOTA-octreotide with Trasis Allinone synthesis module is simple, rapid and stable. The product has high radiochemical purity and can meet the needs of clinical application. In vivo18F-ALF-NOTA-octreotide PET/CT imaging in the patient with NET shows higher T/B ratio, which has obvious advantages compared with 18F-FDG.
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Objective:To optimize the preparation conditions and methods of Al 18F-prostate specific membrane antigen (PSMA)-11 and evaluate the feasibility of clinical transformation. Methods:PSMA- N, N′-bis(2-hydroxy-5-(carboxyethy)benzyl)ethylenediamine- N, N′-diacetic acid (HBED-CC) dissolved in CH 3COONH 4 buffer (pH=4.8) was reacted with AlCl 3·3H 2O dissolved in pure water at a molar ratio of 1∶1 (60 ℃, 10 min), and then purified by tC18 column and freeze-dried to obtain [Al]-PSMA-11. [Al]-PSMA-11 was labeled by 18F - and the effects of reaction temperature and pH value on the labeling rate were investigated. The labeled products were purified by tC18 column and filtered through sterile filter to obtain Al 18F-PSMA-11. The comparison of biodistribution between Al 18F-PSMA-11 and 68Ga-PSMA-11 was analyzed on 5 healthy volunteers (age (56±8) years). The differences of SUV max between two groups were analyzed by independent-sample t test. Besides, the early and delayed imaging of Al 18F-PSMA-11 PET/CT were performed on a patient (70 years old) with recurrent prostate cancer for assessment of its potential for prostate cancer recurrence monitoring. Results:The labeling rate was (42.3±3.2)% reacting in aqueous phase (60 ℃, pH=4.8) for 15 min. After being purified with tC18 cartridge, the radiochemical purity of the product was still more than 95% after placement at room temperature for 3 h. Preliminary application demonstrated that there was no significant difference in the biodistribution of Al 18F-PSMA-11 and 68Ga-PSMA-11 among lacrimal gland, parotid gland, submandibular gland, liver, spleen, kidney, bladder and part of intestine and SUV max of targeted organs were also not different ( t values: 0.19-1.95, all P>0.05) between two groups. Multiple bone metastases were observed by Al 18F-PSMA-11 PET/CT delayed imaging (3 h) in a patient with recurrent prostate cancer. Conclusion:Al 18F-PSMA-11 produced with pre-conjugated [Al]-PSMA-11 meets the requirement of the PET imaging application, and it has good potential of localization and imaging for prostate cancer metastatic lesions.
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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 compare the clinical utility of 18F-fibroblast activating protein inhibitor (FAPI)-42 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging in newly diagnosed lung cancer patients. Methods:From May 2020 to September 2021, the images of 43 lung cancer patients (32 males, 11 females, age: 37-80 years) who pathologically confirmed and received 18F-FDG and 18F-FAPI-42 PET/CT within 2 weeks in the First Affiliated Hospital of Guangzhou Medical University were prospectively analyzed. The maximum standardized uptake value (SUV max) of 18F-FDG and 18F-FAPI-42 and the number of lesions detected by 2 imaging methods were compared by using paired t test and Wilcoxon rank sum test. Results:The 43 newly diagnosed lung cancer patients included 35 adenocarcinoma, 2 squamous cell carcinoma, 4 small cell lung cancer, and 2 high-grade neuroendocrine tumors. 18F-FAPI-42 had a very high tumor uptake (SUV max: 12.24±3.97) and lesion detection rate (positive rate: 100%(37/37)) in primary lung adenocarcinoma and squamous cell carcinoma. The uptake of 18F-FAPI-42 in lymph node (10.13±5.43), pleura (6.75(4.96, 8.58)) and bone lesion (7.18(4.33, 9.66)) were significantly higher than those of 18F-FDG (6.35±3.30, 2.69(1.81, 5.00), 4.38(2.96, 6.36); t=12.19, z values: 5.47, 5.79, all P<0.001). In lung adenocarcinoma and squamous cell carcinoma, although the uptake of 18F-FAPI-42 in brain metastases was significantly lower than that of 18F-FDG (0.72(0.15, 1.82) vs 6.53(4.65, 9.34); z=6.42, P<0.001), the tumor/background (T/B) ratio was significantly higher than that of 18F-FDG (3.54(1.15, 14.88) vs 0.96(0.77, 1.04); z=6.05, P<0.001). In lung adenocarcinoma and squamous cell carcinoma, the number of lesions detected by 18F-FAPI-42 PET/CT was significantly more than that of 18F-FDG (lymph node: 6.0(2.3, 11.5) vs 4.5(2.0, 10.8); brain: 2.0(1.0, 3.0) vs 0.0(0.0, 0.0); pleura: 6.0(2.8, 10.0) vs 4.0(0.8, 5.5); z values: 2.16, 3.10, 2.04, all P<0.05). However, in high-grade neuroendocrine tumors and small cell lung cancer, the SUV max of 18F-FAPI-42 in primary lesions (8.05±2.60), lymph node lesions (5.98±2.21) and brain lesions (0.44(0.13, 0.82)) were lower than those of 18F-FDG (16.28±5.17, 12.30±5.47, 4.94(4.84, 6.25); t values: 3.58, 7.52, z=3.06, all P<0.05). Conclusions:In lung adenocarcinoma and squamous cell carcinoma, 18F-FAPI-42 has a very high tumor uptake and lesion detection rate in primary tumor. In addition, compared with 18F-FDG PET/CT, 18F-FAPI-42 PET/CT shows clearer tumor contours and more lesions. Therefore, 18F-FAPI-42 is more suitable for preliminary staging of lung adenocarcinoma and squamous cell carcinoma than 18F-FDG, while the opposite is true in small cell lung cancer and high-grade neuroendocrine tumors.
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Objective@#To explore the biodistribution and quantitative value of 18F-Flurpiridaz in mini-swine, and compare with 13N-NH3·H2O.@*Methods@#Ten Bama mini-swine were divided into normal group and myocardial infarction group (n=5 in each group). Normal group was not treated and myocardial infarction group was modeled by thoracotomy and coronary artery ligation. Both groups were preceded by 13N-NH3·H2O imaging, followed by 18F-Flurpiridaz imaging (time interval >40 min). Injection dosage of 2 tracers was the same (185-370 MBq). 18F-Flurpiridaz whole-body PET/CT imaging was also performed in normal group. Biological distribution of 18F-Flurpiridaz was observed, and the ratio of radioactive uptake of 18F-Flurpiridaz between myocardium and adjacent tissues or organs was calculated. Image quality score and rest myocardial blood flow (rMBF) of 2 imaging tracers in normal group were measured and compared. MPI image quality score, cardiac function parameters such as summed rest score (SRS), myocardial infarction area percentage, total perfusion defect (TPD), and left ventricular ejection fraction (LVEF) of 2 imaging tracers were compared in myocardial infarction group. Data was analyzed by paired t test.@*Results@#In normal group, 18F-Flurpiridaz in the myocardium was clearly observed, with high radioactive uptake maintaining within 2 h postinjection. The radioactivity count ratios of left ventricular myocardium to cardiac pool, the lungs and liver were high (5.19-12.87, 4.17-50.51, 2.08-6.92). The quality of 18F-Flurpiridaz MPI images in both groups was excellent (10/10). The rMBF (ml·g-1·min-1) in different regions of left ventricle measured by 18F-Flurpiridaz and 13N-NH3·H2O imaging were not significantly different (left anterior descending: 0.98±0.06 vs 0.92±0.13; left circumflex: 0.98±0.05 vs 0.88±0.12; right coronary artery: 0.95±0.07 vs 0.88±0.15; left ventricle: 0.96±0.07 vs 0.90±0.13; t values: from -1.70 to -0.90, all P>0.05). There was no significant difference in SRS, myocardial infarction area percentage, TPD, rMBF or LVEF between 18F-Flurpiridaz and 13N-NH3·H2O (SRS: 10.6±4.1 vs 9.2±4.6; myocardial infarction area percentage: (15.2±9.0)% vs (12.6±6.6)%; TPD: (11.6±6.3)% vs (9.6±3.9)%; LVEF: (68.6±11.1)% vs (71.4±11.3)%; t values: -2.33-2.75, all P>0.05).@*Conclusions@#Comparing with 13N-NH3·H2O, 18F-Flurpiridaz has the advantages of good MPI image quality, accurate measurement of cardiac function parameters and quantitative potential of myocardial blood flow, which make it as a promising positron myocardial perfusion imaging agent.
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Objective@#To investigate the biodistribution of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[2-18F-fluroethoxy]ethoxymethyl]-1H-1, 2, 3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone (18F-MyoZone) and evaluate its clinical potential as a PET myocardial perfusion imaging (MPI) tracer in mini-swine.@*Methods@#18F-MyoZone was prepared. Twelve Bama mini-swine were intravenously injected with approximately 111 MBq of 18F-MyoZone to evaluate PET imaging characteristics. Whole-body PET scans were performed at the timing of 5, 20, 40, 60 and 120 min postinjection to measure time-dependent mean standardized uptake value (SUVmean) in multiple organs of health animals (n=6). SUVmean ratios of myocardium/liver and myocardium/lung over time were then calculated. Mini-swine with induced acute myocardial infarction (n=3) and chronic myocardial ischemia (n=3) accompanying with health mini-swine (n=3) were utilized to evaluate the diagnostic capability of 18F-MyoZone PET MPI.@*Results@#The typical decay-corrected radiochemical yield of 18F-MyoZone reached (52.0±4.3)%(n=3) with a high radiochemical purity (>98%). In the biodistribution study, high initial myocardial uptake (SUVmean=10.40±2.40 at 5 min postinjection) and remarkable myocardial retention (SUVmean=9.30±2.00 at 120 min postinjection) were observed. The adjacent organs (like the liver and lungs) indicated low tracer uptake and rapid clearance. The heart/liver and heart/lung SUVmean ratios were 4.77±0.91 and 17.14±5.84 respectively at 5 min postinjection, with an increase to 11.16±1.38 and 21.69±7.09 at 120 min postinjection. In the MPI study of mini-swine, normal myocardium demonstrated uniform tracer distribution with clearly visualizable myocardial boundary, infarct myocardium and severe ischemia myocardium performed intense resting perfusion defect, and ischemia myocardium revealed reversible perfusion defect by stress/rest MPI. The myocardial image quality remained stable within 120 min postinjection.@*Conclusions@#MPI with 18F-MyoZone exhibits high initial myocardial uptake and low extracardiac activities in adjacent organs. Advantages in early imaging and wide diagnostic time window make it a promising PET MPI tracer.
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6-[18F]fluoro-L-dopa (18F-DOPA) is a levodopa analogue. 18F-DOPA PET/CT imaging is considered as an ideal tool in the diagnosis and evaluation of Parkinson′s disease, brain tumors, pheochromocytoma/paraganglioma, neuroblastoma, gastrointestinal carcinoid, medullary thyroid cancer and congenital hyperinsulinemia. This paper reviews the synthesis, mechanism of localization, imaging procedures, clinical indications and research advances of 18F-DOPA.
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Objective To explore the biodistribution and quantitative value of 18F-Flurpiridaz in mini-swine,and compare with 13N-NH3 · H2O.Methods Ten Bama mini-swine were divided into normal group and myocardial infarction group (n=5 in each group).Normal group was not treated and myocardial infarction group was modeled by thoracotomy and coronary artery ligation.Both groups were preceded by 13N-NH3 · H2O imaging,followed by 18F-Flurpiridaz imaging (time interval ＞40 min).Injection dosage of 2 tracers was the same (185-370 MBq).18F-Flurpiridaz whole-body PET/CT imaging was also performed in normal group.Biological distribution of 18F-Flurpiridaz was observed,and the ratio of radioactive uptake of 18F-Flurpiridaz between myocardium and adjacent tissues or organs was calculated.Image quality score and rest myocardial blood flow (rMBF) of 2 imaging tracers in normal group were measured and compared.MPI image quality score,cardiac function parameters such as summed rest score (SRS),myocardial infarction area percentage,total perfusion defect (TPD),and left ventricular ejection fraction (LVEF) of 2 imaging tracers were compared in myocardial infarction group.Data was analyzed by paired t test.Results In normal group,18F-Flurpiridaz in the myocardium was clearly observed,with high radioactive uptake maintaining within 2 h postinjection.The radioactivity count ratios of left ventricular myocardium to cardiac pool,the lungs and liver were high (5.19-12.87,4.17-50.51,2.08-6.92).The quality of 18F-Flurpiridaz MPI images in both groups was excellent (10/10).The rMBF (ml · g-1 · min-1) in different regions of left ventricle measured by 18F-Flurpiridaz and 13N-NH3 · H2O imaging were not significantly different (left anterior descending:0.98±0.06 vs 0.92±0.13;left circumflex:0.98±0.05 vs 0.88±0.12;right coronary artery:0.95±0.07 vs 0.88±0.15;left ventricle:0.96±0.07 vs 0.90±0.13;t values:from-1.70 to-0.90,all P＞0.05).There was no significant difference in SRS,myocardial infarction area percentage,TPD,rMBF or LVEF between 18F-Flurpiridaz and 13N-NH3 · H2O (SRS:10.6±4.1 vs 9.2±4.6;myocardial infarction area percentage:(15.2±9.0)％ vs (12.6±6.6)％;TPD:(11.6±6.3)％ vs (9.6±3.9)％;LVEF:(68.6±11.1)％ vs (71.4±11.3)％;t values:-2.33-2.75,all P＞0.05).Conclusions Comparing with 13N-NH3 · H2O,18F-Flurpiridaz has the advantages of good MPI image quality,accurate measurement of cardiac function parameters and quantitative potential of myocardial blood flow,which make it as a promising positron myocardial perfusion imaging agent.
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Objective To investigate the biodistribution of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[2-18 F-fluroethoxy] ethoxymethyl]-1H-1,2,3-triazol-4-yl] methyl] phenylmethoxy]-3(2H)-pyridazinone (18F-MyoZone) and evaluate its clinical potential as a PET myocardial perfusion imaging (MPI) tracer in miniswine.Methods 18F-MyoZone was prepared.Twelve Bama mini-swine were intravenously injected with approximately 111 MBq of 18F-MyoZone to evaluate PET imaging characteristics.Whole-body PET scans were performed at the timing of 5,20,40,60 and 120 min postinjection to measure time-dependent mean stand-ardized uptake value (SUVmean) in multiple organs of health animals (n =6).SUVmean ratios of myocardium/liver and myocardium/lung over time were then calculated.Mini-swine with induced acute myocardial infarction (n =3) and chronic myocardial ischemia (n =3) accompanying with health mini-swine (n =3) were utilized to evaluate the diagnostic capability of 18F-MyoZone PET MPI.Results The typical decay-corrected radiochemical yield of 18 F-MyoZone reached (52.0±4.3)％ (n =3) with a high radiochemical purity (＞98％).In the biodistribution study,high initial myocardial uptake (SUVmean =10.40±2.40 at 5 min postinjection) and remarkable myocardial retention (SUVmean =9.30±2.00 at 120 min postinjection) were observed.The adjacent organs (like the liver and lungs) indicated low tracer uptake and rapid clearance.The heart/liver and heart/lung SUVmean ratios were 4.77±0.91 and 17.14±5.84 respectively at 5 min postinjection,with an increase to 11.16± 1.38 and 21.69±7.09 at 120 min postinjection.In the MPI study of miniswine,normal myocardium demonstrated uniform tracer distribution with clearly visualizable myocardial boundary,infarct myocardium and severe ischemia myocardium performed intense resting perfusion defect,and ischemia myocardium revealed reversible perfusion defect by stress/rest MPI.The myocardial image quality remained stable within 120 min postinjection.Conclusions MPI with 18F-MyoZone exhibits high initial myocardial uptake and low extracardiac activities in adjacent organs.Advantages in early imaging and wide diagnostic time window make it a promising PET MPI tracer.
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6-[18F]fluoro-L-dopa (18F-DOPA) is a levodopa analogue.18F-DOPA PET/CT imaging is considered as an ideal tool in the diagnosis and evaluation of Parkinson's disease,brain tumors,pheochromocytoma/paraganglioma,neuroblastoma,gastrointestinal carcinoid,medullary thyroid cancer and congenital hyperinsulinemia.This paper reviews the synthesis,mechanism of localization,imaging procedures,clinical indications and research advances of 18F-DOPA.
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Objective To explore the relationship between the maximum standardized uptake value ( SUVmax ) of 18 F-fluoromisonidazole ( FMISO) PET/CT and the pathological classification, differentiation, T stage and primary tumor volume of nasopharyngeal carcinoma ( NPC) . Methods A retrospective analysis was performed on 41 patients with NPC (31 males, age 18-74 years;10 females, age 35-67 years) who underwent head and neck 18 F-FMISO PET/CT from 2012 to 2015. The relationship between the clinicopath-ological parameters (pathological classification, differentiation, T stage, tumor volume) of primary lesion and SUVmax were analyzed. Mann-Whitney u test, approximate t test and Spearman correlation were used for data analysis. Results There was no significant difference in SUVmax between non-keratinizing carcinoma and squamous cell carcinoma ( u=183.5, P>0.05) , nor between the differentiated carcinoma and undiffer-entiated carcinoma( t'=-1.23, P>0.05) . SUVmax of T1-T2 primary tumor was significantly lower than that of T3-T4 tumor (1.52±0.43 vs 2.05±0.85; t'=-2.60, P<0.05), and SUVmax was correlated with primary tumor volume ( rs=0.488, P<0.05) . Conclusions The hypoxic degree is related with T stage and primary tumor volume in NPC. The combination analysis of T stage and tumor size will contribute to the assessment of oxygen level and prognosis of primary NPC.
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Objective To synthesize a novel 18 F labeled probe targeting translocator protein ( TSPO) ligand 2-( 5, 7-diethyl-2-( 4-( 2-fluoroethoxy ) phenyl ) pyrazolo [ 1, 5-a ] pyrimidin-3-yl )-N, N-diethylacet-amide (VUIIS1008), and evaluate its biodistribution and imaging in rheumatoid arthritis (RA) model. Methods The tosylate substrate was labeled with 18 F using a tosyloxy for fluorine nucleophilic aliphatic substitution to obtain 18 F-VUIIS1008. The labeling efficiency, radiochemical purity, and stability in vitro were determined. In vitro cellular uptake and competitive binding assay were performed on RAW264.7 mac-rophage cells. Biodistribution and microPET/CT imaging were investigated on RA mice established by Com-plete Freund's Adjuvant. Two-sample t test was used to analyze the data. Results 18 F-VUIIS1008 was syn-thesized with the labeling yield up to (41.00±5.00)％, the radiochemical purity>98.00％, and the specific radioactivity >1. 52 × 108 MBq/mmol. 18 F-VUIIS1008 was highly stable with the radiochemical purity >98. 00％ at 4 h after incubation in mouse serum. In vitro, it also exhibited high specific TSPO binding in RAW264.7 macrophage cells. The uptake ratio was (14.00±0.30)％ at 1 h after incubation, and decreased significantly ((4.00±0.70)％;t=12.894, P<0.05) after adding excessive unlabeled VUIIS1008. The half maximal inhibitory concentration (IC50) of 18F-VUIIS1008 binding to TSPO was 0.05 nmol/L in RAW264.7 macrophage cells. In vivo distribution results showed that the uptake of 18 F-VUIIS1008 in the left arthritic ankles reached the peak value of (1.33±0.02) percentage activity of injection dose per gram of tissue (％ID/g) at 1 h after injection. The radioactivity ratio of left ankle arthritic tissue to blood ( A/B) and to normal muscle ( A/M) was 4.40±0.22 and 1.65±0.07 respectively. MicroPET/CT imaging demonstrated that 18F-VUIIS1008 could specifically target and retained in the inflammation site. Conclusion 18 F-VUIIS1008 can be easily synthe-sized with high radiochemical purity and can clearly visualized in RA imaging with low background, suggesting its potential as a novel promising molecular probe targeting TSPO for RA PET imaging.
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Objective To explore the efficiency of 6-18 F-fluoro-L-3,4-dihydroxyphenylalanine (18 F-FDOPA) PET/CT imaging in the diagnosis of pheochromocytoma/paraganglioma (PPGLs). Methods Twenty-six patients (15 males, 11 females;age:13-76 years) who were suspected of PPGLs with adrenal or retro-peritoneal mass were enrolled into this prospective study. All patients underwent 18 F-FDOPA PET/CT ima-ging. The clinical data, laboratory data and imaging results were collected. Region of interest ( ROI) was drawn on the liver and lesions, and the mean standardized uptake value ( SUVmean ) of the liver and the max-imum standardized uptake value ( SUVmax ) of lesions were calculated, as well as the ratio of tumor/lesion ratio ( T/L) . Based on the pathological results considered as the gold standard, the diagnostic efficiency of 18 F-FDOPA PET/CT imaging in PPGLs was calculated and compared with that of CT/MR. Besides, receiv-er operating characteristic ( ROC) curve analysis of T/L was used. Results Twenty-five patients were path-ologically confirmed, including 12 patients with PPGLs and 13 patients with non-PPGLs. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 18 F-FDOPA PET/CT ima-ging was 11/12, 12/13, 92.00％(23/25), 11/12 and 12/13, respectively. The area under the ROC curve of T/L was 0.978, with the cut-off value of 1.55. 18 F-FDOPA PET/CT imaging totally detected 29 positive foci, including 12 of pheochromocytoma (PCC) and 17 of paraganglioma (PGL). Among those 18F-FDOPA positive PGL foci, 11 were detected by CT/MR, while 6 with diameter less than 1 cm were missed. Conclu-sion 18 F-FDOPA PET/CT imaging can detect more small PGL lesions than CT/MR, suggesting that it may be a proper imaging modality of PPGLs.
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PET serves as one of the most advanced imaging modalities,and its development depends on the improvement of radiotracers.Among numerous positron isotopes,18 F appears to be the best radionuclide candidate for PET radiotracers by virtue of its favorable physical characteristics.18 F-labeled aromatic radiotracers have been widely investigated by researchers due to its special metabolic stability.However, the development and application of 18 F-labeled aromatic radiotracers have been limited due to lacking of radiochemical methods to obtain products with high selectivity,high radioactivity and high purity.This review focuses on the new labeling methods of 18 F-labeled aromatic radiotracers from the aspects of electrophilic and nucleophilic substitution reactions.
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PET myocardial perfusion imaging ( MPI) is increasingly used in non-invasive detection and evaluation of coronary artery disease ( CAD) . However, the wide application of common PET MPI a-gents ( 15 O-H2 O, 13 N-NH3 ·H2 O, 82 Rb) in clinic is limited by their inherent shortcomings. The develop-ment of 18 F-Flurpiridaz has opened up a new field of positron blood flow imaging agents. Preliminary results of pre-clinical and clinical trials showed that 18 F-Flurpiridaz has important properties ( high myocardial up-take, high resolution of perfusion defect, slow myocardial clearance, stable target/non-target ratio, and the ability of quantitative myocardial flow analysis) as an ideal PET MPI agent, so it has a good clinical appli-cation prospect. In this paper, the present application and progress of 18 F-Flurpiridaz PET MPI are re-viewed.