Androgen Receptor Imaging in the Management of Hormone-Dependent Cancers with Emphasis on Prostate Cancer.

Prostate cancer is dependent on the action of steroid hormones on the receptors. Endocrine therapy inhibits hormone production or blocks the receptors, thus providing clinical benefit to many, but not all, oncological patients. It is difficult to predict which patient will benefit from endocrine therapy and which will not. Positron Emission Tomography (PET) imaging of androgen receptors (AR) may provide functional information on the likelihood of endocrine therapy response in individual patients. In this article, we review the utility of [18F]FDHT-PET imaging in prostate, breast, and other hormone-dependent cancers expressing AR. The methodologies, development, and new possibilities are discussed as well.

Optimization of labeling methods for a novel prostate cancer PET probe Al 18F-PSMA-137 / 中华核医学与分子影像杂志

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.

Evaluation of the effect of linker on novel targeted PSMA PET probe / 中华核医学与分子影像杂志

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.

Research progress on isotope-exchange-based 18F-labeling methods / 中华核医学与分子影像杂志

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.

Automatic radiolabeling of the norepinephrine transporter targeted tracer 18F-mFBG and evaluation of 18F-mFBG PET/CT imaging in pheochromocytoma / 中华核医学与分子影像杂志

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.

Automatic synthesis of 18F-AlF-NOTA-octreotide and PET/CT imaging in neuroendocrine tumor / 中华核医学与分子影像杂志

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.

Preparation of Al 18F-PSMA-11 and its preliminary PET/CT imaging / 中华核医学与分子影像杂志

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.

Preparation and microPET imaging of extradomain-B fibronectin specific probe 18F-AlF-NOTA-PEG 4-ZD2 / 中华核医学与分子影像杂志

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.

Automatic synthesis and in vivo imaging of Al 18F-NOTA-FAPI-04 / 中华核医学与分子影像杂志

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.

Comparison of clinical utility of 18F-FAPI-42 and 18F-FDG PET/CT imaging in the diagnosis of newly diagnosed lung cancer / 中华核医学与分子影像杂志

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.

Comparison of 18F-Flurpiridaz and 13N-NH3·H2O PET/CT myocardial perfusion imaging in animal experiments / 中华核医学与分子影像杂志

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.

Experimental research of PET imaging with novel 18F-labeled myocardial perfusion imaging tracer: 18F-MyoZone / 中华核医学与分子影像杂志

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.

Research progress of 6-18Ffluoro-L-dopa PET/CT imaging / 中华核医学与分子影像杂志

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.

Comparison of 18F-Flurpiridaz and 13N-NH3 · H2O PET/CT myocardial perfusion imaging in animal experiments / 中华核医学与分子影像杂志

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.

Experimental research of PET imaging with novel 18F-labeled myocardial perfusion imaging tracer: 18F-MyoZone / 中华核医学与分子影像杂志

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.

Research progress of 6-18F fluoro-L-dopa PET/CT imaging / 中华核医学与分子影像杂志

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.

Improvement of Al18 F-PSMA-BCH preparation and its preliminary imaging study / 中华核医学与分子影像杂志

Objective To optimize the radiolabeling of prostate specific membrane antigen (PSMA)-targeted probe Al18 F-PSMA-BCH (Beijing Cancer Hospital) and to evaluate its potential for clinical trial and translation. Methods The mixture of PSMA-BCH, AlCl3 , potassium biphthalate and no-carrier loaded 18F- was reacted at 110 ℃ for 15 min, then purified by Sep-Pak Light C18 column and filtered through 0.22 μm sterile filter to obtain Al18 F-PSMA-BCH. The radiolabeled yield and radiochemical purity were determined. Al18 F-PSMA-BCH PET/ CT imaging was performed on 5 healthy volunteers (age: (68±7) years) for bio-distribution and radiation dosimetry estimate and on 1 patient (65 years) with recurrent prostate cancer. Re-sults The non-decay-corrected radiochemical yield of Al18F-PSMA-BCH was (38. 0±3.5)％ with the radiochem-ical purity >99％ and the specific activity of (16.4±4.4) MBq/ nmol. Al18 F-PSMA-BCH was stable in saline at room temperature. In healthy volunteers, radioactivity was mainly accumulated in the bladder, kidneys, lacrimal glands, parotid glands and submandibular glands, of which kidneys were the most critical organs with the dosim-etry of (152.89±33.43) μGy/ MBq, while bones showed lower uptake ((11.10±1.23) μGy/ MBq) than most or-gans. The effective dose of whole body was (0.0135 ±0.0025) mSv/ MBq. Multiple bone metastases were ob-served by Al18F-PSMA-BCH PET/ CT imaging in a patient with recurrent prostate cancer. Conclusions Al18 F-PSMA-BCH prepared with the pH controller of potassium biphthalate holds the potential for the diagnosis, staging and monitoring recurrence of prostate cancer.

18F-Alfatide n automated preparation based on 18 F-minireactor and microPET/CT imaging in tumor / 中华核医学与分子影像杂志

Objective To develop the automated preparation of 18F-Alfatide II using newly-designed 18F-minireactor and perform 18F-Alfatide D microPET/CT imaging in tumor.Methods The automated preparation of 18F-Alfatide H was developed by using 18F-microreactor and water phase Al18F-chelating method,and the radiochemical yield and quality analysis were measured.The nude mice bearing breast tumor ZR-75-1 and nasopharyngeal tumor CNE1 were established(n = 3 respectively).MicroPET/CT imaging was performed at 0.5,1.0 and 2.0 h after the injection of 18F-Alfatide II.The region of interest(ROI)was depicted and the tumor/muscle(T/M)ratio was calculated.Results 18F-Alfatide II was automatically prepared with the total synthesis time of 40 min,the radiochemical yield of(28±6)%(no decay corrected,n=11),and the radiochemical purity >97%.All quality analysis indexes accorded with the radiopharmaceutical requirements.18F-Alfatide II microPET/CT images of ZR-75-1 and CNE1 tumors were clear due to the high radioactivity uptake of tumor lesions(T/M ratio was greater than 4.0 at 1.0 h after injection).Conclusion Based on the 18F-minireactor,the,8F-Alfatide II can be prepared successfully with short synthesis time and high radiochemical yield,which can help the application studies in 18F-Alfatide II microPET/CT imaging.

Preclinical microPET imaging in tumor-bearing nude mice and pharmacokinetic studies of 18F-Alfatide II / 中华核医学与分子影像杂志

Objective To assess the imaging characteristics of 18F-Alfalide II in different tumorbearing mice and pharmacokinetics in Beagle dogs.Methods BALB/c nude mice(n-24)were used for subcutaneous tumor models(A549 and U87MG),orthotopic lung cancer models(A549)and orthotopic breast cancer models(MDA-MB-231)(n=6 in each group).18F-Alfatide II and 18F-fluorodeoxyglucose(FDG)microPET/CT images were compared in the 4 types of tumor-bearing nude mice models.18F-Alfatide II blocking experiment,biodistribution experiment and imaging studies in tumors of different growth cycles were performed in A549 subcutaneous tumor-bearing nude mice models.Pharmacokinetic experiments were carried out in Beagle dogs(n = 6)and CD-1 mice(n = 9).Two-sample t test was used to analyze the data.Results Compared with 18F-FDG,18F-Alfatide II microPET/CT images showed better imaging quality and contrast in subcutaneous A549,U87MG tumors and orthotopic A549(tumor/heart:4.50±1.17 vs 0.95±0.31;t = 4.125,P<0.01),orthotopic MDA-MB-231(tumor/muscle:6.60±1.53 vs 0.92±0.43;t = 3.984,P<0.01)transplantation nude mice models.18F-Alfatide II could specifically target A549 tumors,and the tumor uptake of 18F-Alfatide II was reduced by about 75% after pre-injection with cyclo(Arg-Gly-Asp-D-Tyr-Lys)(c(RGDyk)).18F-Alfatide II was rapidly cleared from the blood of Beagle dogs(T1/2 was(57.34±11.69)min).It was cleared in the form of prototype drug and(69.24±6.82)% of cumulative dose was excreted through the urine within 4 h after administration.Conclusions 18F-Alfatide II shows a higher target/non-target ratio than,18F-FDG in the imaging of A549,MDA-MB-231 and U87MG tumor-bearing nude mice models,which is more conducive to the diagnosis of tumor.18F-Alfatide II has excellent pharmacokinetic properties.

Diagnostic value of a novel RGD-peptide based tracer 18F-Alfatide II for breast cancer / 中华核医学与分子影像杂志

Objective To investigate the biodistribution of 18F-Alfatide II in patients with breast diseases and to compare its uptake with 18F-fluorodeoxyglucose(FDG)uptake.Methods A total of 44 female patients(age:(50.7±8.0)years)with clinically suspected breast cancer from December 2015 to May 2017 were prospectively enrolled and underwent 18 F-Alfatide II and 18F-FDG PET/CT prior to treatment.By drawing regions of interest in normal organs and breast lesions,differences between 18F-Alfatide II uptake and l8F-FDG uptake were evaluated in all patients.Paired t test,two-sample t test and Wilcoxon rank sum test were used for data analysis.Results There were 53 breast lesions confirmed by histopathology in 44 patients.Among them,42 lesions were malignant and the others were benign.The uptake of 18F-Alfatide II was very low in the brain,vocal cords,lungs,blood pool and muscle.But the renal cortex and bladder had high 18F-Alfatide II accumulation.Different levels of 18F-Alfatide II uptake were found in other normal organs including normal breast tissue.There were differences(t values:2.04-41.65,all P<0.05)between 18F-Alfatide II and 18F-FDG maximum standardized uptake value(SUVmax)and mean standardized uptake value(SUVmean)in many normal organs except for the choroid plexus,salivary glands,liver,colon and normal breast tissue.The uptake of 18F-Alfatide II was significantly lower than 18F-FDG in breast cancer lesions(SUVmax:3.77±1.78 vs 7.37±4.48,SUVmean:2.25±0.98 vs 4.54±2,82;t values:4.89,4.82,both P< 0.05),but it was still higher in benign breast lesions(SUVmax:2.37±1.62,SUVmean:1.50±0.92;t val-ues:2.35,2.29,both P<0.05).Also,target/non-target(T/NT)of 18F-Alfatide II in breast cancer lesions was higher than that in benign breast lesions(5.32±3.08 vs 2.60±2.37;t = 2.72,P<0.05).Condusion The biodistribution of 18F-Alfatide II in patients is favorable and 18F-Alfatide II can be clinically used for breast cancer imaging.