11C-β-CFT:多巴胺转运蛋白显像剂的合成及其在帕金森病诊断中的应用

目的 探讨脑多巴胺转运蛋白显像剂¹¹C-甲基-N-2β-甲基酯-3β-(4-F-苯基)托烷(¹¹C-β-CFT)的PET/CT显像在早期帕金森病诊断中的临床应用价值。方法 将第一步反应生成的¹¹C-CH3I在线转换成Triflate-¹¹CH后与前体2β-甲基酯-3β-(4-F-苯基)去甲基托烷进行室温反应,反应结束后加水转移反应液到C18柱上进行纯化,产品¹¹C-β-CFT用乙醇从C18柱上洗脱后加水混匀得到终产品。5例轻度帕金森病患者静脉注射¹¹C-β-CFT后约60min后对其进行脑部PET/CT显像。结果 ¹¹C-β-CFT的总合成时间约16 min,放化纯度>98%,比活度>2 GBq/μmol,未校正合成产率为(25.0±5.0)%。轻度帕金森病患者脑PET/CT显示双侧前壳核、后壳核¹¹C-β-CFT摄取明显减少,以患病侧壳核区域最为显著。结论 全自动化制备¹¹C-...     

不同侵袭转移特性肝癌模型的 18F-FDG和2- 18F-乙酸盐联合显像

目的:探讨¹⁸F-FDG和2-¹⁸F-乙酸盐联合显像在区分不同转移潜能的肝癌裸鼠模型中的意义。方法:以人肝癌细胞株Hep G2和QGY7701为研究对象进行体外侵袭实验,判断细胞侵袭转移能力的大小。通过体外核素摄取实验观察两株肝癌细胞¹⁸F-FDG和2-¹⁸F-乙酸盐的摄取差异性,并建立皮下荷瘤模型进一步观察两种示踪剂的活体显像特征,绘制感兴趣区（ROI）并计算瘤/非瘤比值。结果:Hep G2细胞体外侵袭能力大于QGY7701（P<0.05）。Hep G2细胞的¹⁸F-FDG和2-¹⁸F-乙酸盐摄取率均高于QGY7701,其摄取差异有统计学意义（P<0.05）。两株细胞¹⁸F-FDG摄取率与侵袭能力呈正相关（r=0.657,P<0.05）。活体显像中Hep G2肿瘤组织的¹⁸F-FDG和2-¹⁸F-乙酸盐的摄取值亦高于QGY7701,其中¹⁸F-FDG的摄取差异有统计学意义（P<0.05）。结论:¹⁸F-FDG摄取值能够反映肝癌细胞侵袭转移能力的大小;同时¹⁸F-FDG Micro-PET显像能够区分两种肝癌模型,提示¹⁸FFDG显像有助于预测肝癌的不同侵袭转移潜能力。     

18F-FDG PET/CT双时相显像结合高分辨率CT诊断孤立性肺结节的临床观察

目的分析¹⁸F-氟代脱氧葡萄糖正电子发射断层显像/计算机断层显像(¹⁸F-FDG PET/CT)双时相显像结合高分辨率CT(HRCT)对孤立性肺结节的诊断价值。方法对136例孤立性肺结节患者临床资料进行回顾分析,以术后病理活组织检查结果为金标准,收集2组患者的¹⁸F-FDG PET/CT双时相显像及HRCT诊断结果,比较¹⁸F-FDG PET/CT双时相显像中良性和恶性孤立性肺结节的早期标准摄取值(SUV_早期)、SUV_延期和滞留指数间的差异,分析单纯¹⁸F-FDG PET/CT双时相显像和¹⁸F-FDG PET/CT双时相显像结合HRCT对孤立性肺结节良恶性的诊断价值,对比2种方法对孤立性肺结节恶性典型征象的检出结果。结果 136例孤立性肺结节患者中,良性病变69例、恶性病变67例。¹⁸F-FDG PET/CT双时相显像中,恶性孤立性肺结节的SUV_早期、SUV_...     

18F-FDG PET/CT对宫颈癌术后临床怀疑复发和转移病人中的应用价值

目的观察¹⁸F-氟代脱氧葡萄糖(¹⁸F-FDG)正电子发射断层显像技术/计算机体层扫描(PET/CT)对宫颈癌术后临床怀疑复发与转移患者的诊断价值。方法前瞻性纳入喀什地区第一人民医院2018年7月至2020年11月期间收治的118例宫颈癌术后怀疑复发与转移患者为研究对象,采用随机数字表法其分为观察组(n=59)与对照组(n=59)。对照组予给予以常规血清癌抗原19-9(CA19-9)检测,观察组行¹⁸F-FDG PET/CT检查。2组均以组织病理学结果为金标准,评估2组对宫颈癌怀疑复发与转移的诊断价值并对比组间差异。结果¹⁸F-FDG PET/CT检查诊断对宫颈癌复发及转移的特异度(76.92%)、灵敏度(93.48%)以及准确率(89.83%)均显著高于CA19-9检测(38.46%、60.87%、55.93%),2组比较差异有统计学意义(P<0.05),同时观察组诊断结果与组织病理学结果吻合度较高(Kappa=0.766,P<0.05)。结论¹⁸F-FDG PET/CT检查应用于宫颈癌术后临床怀疑复发与转移的诊断,可清晰显示其状况,灵敏度、准确率等均明显高于血清CA19-9检测。     

21例肺黏膜相关淋巴组织淋巴瘤的CT和18F-氟代脱氧葡萄糖正电子发射计算机断层显像的影像学表现

目的 探讨肺黏膜相关淋巴组织(MALT)淋巴瘤的CT和¹⁸F-氟代脱氧葡萄糖(¹⁸F-FDG)正电子发射计算机断层显像(PET)-CT的影像学表现。方法 回顾性分析经病理结果证实的21例肺MALT淋巴瘤患者的CT及PET-CT影像学资料,并通过Logistic回归分析探讨¹⁸F-FDG亲和力与影像学表现的相关性。结果 21例患者中,共发现60个肺部病灶,其中22个实变样病灶,28个结节或肿块样病灶和10个磨玻璃样病灶。12例为单发病灶,9例为多发病灶,多发病灶患者中,双侧病灶7例,单侧病灶2例。¹⁸F-FDG PET-CT显示,60个病灶中45个为高代谢病灶,15个为低代谢病灶。Logistic回归分析发现,¹⁸F-FDG亲和力与病灶形态及病灶直径相关(P<0.01)。结论 肺MALT淋巴瘤影像学表现多样,可为结节或肿块型、肺炎型及磨玻璃型,多为亲和¹⁸F-FDG的肿瘤,且¹⁸F-FDG亲和力与肿瘤直径及形态相关。     

18F-脱氧葡萄糖正电子发射断层扫描技术诊断乳腺癌及淋巴结转移的效能分析

目的 探讨¹⁸F-脱氧葡萄糖(¹⁸F-FDG)正电子发射断层扫描(PET/CT)技术用于诊断乳腺癌及淋巴结转移的效能,为临床提供参考。方法 选取2021年1月至2022年12月邹平市中心医院收治的120例疑似乳腺癌患者进行回顾性分析,均于术前对其实施¹⁸F-FDG PET/CT检查,以手术病理活检为“金标准”,评估¹⁸F-FDG PET/CT检查诊断乳腺癌及淋巴结转移的效能。结果 120例疑似乳腺癌患者手术病理活检显示,阳性病例80例(66.67%),阴性病例40例(33.33%);80例乳腺癌患者中有腋窝淋巴结转移39例(48.75%),无腋窝淋巴结转移41例(51.25%)。¹⁸F-FDG PET/CT诊断疑似肿瘤病灶阳性病例82例(68.33%),疑似肿瘤病灶阴性病例38例(31.67%):¹⁸F-FDG PET/CT诊断乳腺癌的准确率为80.00%、敏感度为86.25%、特异度为67.50%、阳性预测值为84.15%、阴性预测值为71.05%、Ka...     

成纤维细胞激活蛋白抑制剂PET显像诊断非恶性疾病研究进展

成纤维细胞激活蛋白(FAP)可在活化的成纤维细胞中过度表达。近年来,放射性核素标记的FAP抑制剂(FAPI)已继¹⁸F-FDG之后成为核医学领域中的重要新型正电子显像剂,越来越多地用于非恶性疾病。本文就FAPI PET显像用于诊断非恶性疾病研究进展进行综述。     

18F-前列腺特异性膜抗原-1007 PET/CT显像、11C-胆碱PET/CT显像及单光子发射计算机断层成像术骨显像对前列腺癌骨转移的诊断价值比较

目的探讨¹⁸F-前列腺特异性膜抗原(PSMA)-1007标记的正电子发射体层显像融合计算机体层显像技术(PET/CT)显像、11C-胆碱(11C-CHO)PET/CT显像及单光子发射计算机断层成像术(SPECT)骨显像在前列腺癌骨转移诊断上的差异。方法回顾性分析2018年9月至2020年7月北部战区总医院核医学科收治的43例男性前列腺癌患者的临床资料,年龄(77.47±11.87)岁,年龄范围为55~89岁。所有患者行¹⁸F-PSMA-1007 PET/CT显像、11C-CHO PET/CT显像及SPECT骨显像检查。分别统计¹⁸F-PSMA-1007 PET/CT显像、11C-CHO PET/CT及SPECT骨显像诊断骨转移的阳性例数和阴性例数,计算三种方法各自的灵敏度、特异度、准确性、阳性预测值、阴性预测值,绘制受试者工作特征(ROC)曲线,计算并比较各自曲线下面积(AUC),评价三种检查方法对前列腺癌骨转移的诊断效能。结果 43例前列腺癌患者中,27例患者出现骨转移。¹⁸F-PSMA-1007 PET/CT显像示26例患者发生骨转移,漏诊1例;11C-CHO PET/CT显像示24例患者发生骨转移,误诊1例,漏诊4例;SPECT骨显像示23例患者发生骨转移,误诊3例,漏诊7例,三者诊断前列腺癌骨转移的灵敏度、特异度、准确性分别为96.3%(26/27)、100%(16/16)、97.7%(42/43);85.2%(23/27)、93.8%(15/16)、88.4%(38/43);74.1%(20/27)、81.3%(13/16)、76.7%(33/43)。¹⁸F-PSMA-1007 PET/CT显像、11C-CHO PET/CT和SPECT骨显像ROC曲线的AUC和95%CI分别为0.981(0.885~1.000)、0.913(0.763~0.967)、0.777(0.624~0.889)。三种检查的AUC曲线下面积进行两两比较,差异均有统计学意义(P<0.05)。采用Wilcoxon秩和检验对27例患者三种方法检出的骨转移灶的数量进行两两比较发现,¹⁸F-PSMA-1007 PET/CT显像与SPECT骨显像比较,差异有统计学意义(Z=-2.484,P=0.013),¹⁸F-PSMA-1007 PET/CT显像与11C-CHO PET/CT显像比较,差异无统计学意义(Z=-0.160,P=0.873);11C-CHO PET/CT显像与SPECT骨显像比较,差异有统计学意义(Z=-2.085,P=0.037)。结论 PET/CT显像较SPECT骨显像能发现更多的骨转移灶。¹⁸F-PSMA-1007 PET/CT显像对前列腺癌骨转移诊断的灵敏度、特异度及准确性高于其他两种检查方式。在低前列腺特异性抗原(PSA)的情况下,能够精确地对前列腺癌骨转移做出诊断。     

18F-Fallypride标记前体的反相HPLC测定

18F-Fallypride化学名为(s)-(-)-N-(1-烯丙基吡咯烷-2-氨基甲基)-5-氟[18F]-2, 3-二甲氧基苯甲酰胺(结构式见图1), 是一种安全有效的新型多巴胺D2 受体PET显像剂[1], 与脑内D2受体具有高亲和力和适宜的亲脂性,且所携带的正电子核素18F半衰期短(约110 min), 对人体安全无毒.利用该显像剂结合PET(正电子发射计算机断层显像)、microPET(小动物专用正电子发射计算机断层显像)等可活体、无创、动态地显像以观察脑内多巴胺D2受体变化,为脑神经疾病研究提供了新型的有效手段,为精神分裂症、癫痫、兴奋剂成瘾等的发病机制及防治研究提供了真实、客观的依据[2-5].本实验室在国内首次制备了18F-Fallypride的标记前体,化学名为(s)-(-)-N-(1-烯丙基吡咯烷基-2-氨基甲基)-5-(3-苯-磺酰氧丙基)- 2, 3-二甲氧基苯甲胺(结构式见图2), 可方便临床医师制备18F-Fallypride, 用于多种D2受体相关疾病的即时、早期诊断.18F-Fallypride标记前体的质量控制对于提高18F-Fallypride的合成效率和放射化学纯度、保证18F-Fallypride的显像质量是非常重要的.作者利用高效液相色谱法(HPLC)高效、高灵敏度的分离特点,建立了反相HPLC测定标记前体含量的方法,简便可靠,为标记前体的质控提供了有效手段.现报告如下.     

^18F—Fallypride标记前体的反相HPLC测定

^18F-Fallypride化学名为（s）-（-）-N-（1-烯丙基吡咯烷-2-氨基甲基）-5-氟[墙F]-2，3-二甲氧基苯甲酰胺（结构式见图1），是一种安全有效的新型多巴胺D2受体PET显像剂，与脑内D2受体具有高亲和力和适宜的亲脂性，且所携带的正电子核素坞F半衰期短（约110min），对人体安全无毒。利用该显像剂结合PET（正电子发射计算机断层显像）、micrOPET（小动物专用正电子发射计算机断层显像）等可活体、无创、     

Feasibility of 2–deoxy–2–[18F]fluoro–D–glucose– A85380–PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo

Summary  Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (α₄β₂) nicotinic acetylcholine receptor PET ligand (2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinson's disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2–deoxy–2–[¹⁸F]fluoro–D–glucose–A85380 PET–imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 whole body PET–scans were performed on a Siemens PET/CT biograph^TM 75.4 min±6.7 after i.v. injection of 371.2±58.1 MBq. Average count rate density of left ventricle ROI's and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart–to–lung ratios were calculated in each volunteer and patient. Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart–to–lung ratios in the volunteer group were not different from patients suffering from Parkinson's disease or MSA (3.2 ± 0.5 vs 3.2 ± 0.8 and 2.96±0.7, mean ± SD), respectively. Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 PET scans both in cardiac–healthy subjects and patients suffering from Parkinson's disease or multiple system atrophy. The heart– as well as the lung–tracer uptake was almost constant throughout all subjects leading to a good target–to–background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors. The Article “Feasibility of 2-deoxy-2-[¹⁸F]fluoro-D-glucose-A85380-PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo” by J. Bucerius et al. (the online version can be found at has been published in issue 95 (2006):105–109. Unfortunately a wrong notation for the tracer was given. Instead of 2-deoxy-2-[¹⁸F]fluoro-D-glucose-A85380 it should be 2-[¹⁸F]-A85380. The publisher apologies for any inconvenience caused by this mistake.     

Pharmacological and toxicological evaluation of 2-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-F-A-85380), a ligand for imaging cerebral nicotinic acetylcholine receptors with positron emission tomography

2-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]F-A-85380), a positron emission tomography (PET) radioligand for neuronal alpha4beta2(*) nicotinic acetylcholine receptors, was evaluated for its pharmacology and safety. In the Ames test for mutagenicity, 2-F-A-85380 was without effect in five bacterial strains. No evidence of gross pathology or histopathological changes occurred in either 2-day acute (0.4-4000 nmol/kg i.v.) or 14-day expanded acute (40-4000 nmol/kg i.v.) toxicity studies in mice. Similarly, hematology and serum chemistry values in rhesus monkeys administered 60 nmol/kg i.v. were not affected over 14 days. Like nicotine, 2-F-A-85380 produced convulsions in mice at very high doses. The ED(50) value of 2-F-A-85380 for eliciting tonic-clonic convulsions (5.0 micromol/kg i.v.) was nearly 4 times greater than that of nicotine (ED(50) = 1.4 micromol/kg i.v.). Lower doses of 2-F-A-85380 (30-300 nmol/kg i.v.) and nicotine (20-400 nmol/kg i.v.) increased systolic and diastolic blood pressure, heart rate, and cardiac contractility in rats. Notably, the PR, QRS, or QTc intervals of the rat electrocardiogram were unaffected by either drug. Dosimetry studies indicated that the urinary bladder wall was the critical organ and total radiation exposure was within acceptable limits. Estimated doses of 2-F-A-85380 required to elevate blood pressure and heart rate by 10% ranged from 40 to 58 nmol/kg i.v. Nevertheless, the estimated radiopharmaceutically relevant dose of [(18)F]2-F-A-8380 required for initial PET imaging studies, 10 pmol/kg, is less than 1/4000th of the doses calculated (40-58 nmol/kg i.v.) to elevate blood pressure and heart rate by 10% in humans and should elicit no clinically significant effects and have acceptable dosimetry.     

Evaluation of drug penetration into the brain: a double study by in vivo imaging with positron emission tomography and using an in vitro model of the human blood-brain barrier

The blood-brain barrier (BBB) permeabilities of 11 compounds were measured both in vitro with a newly developed coculture-based model of human BBB and in vivo with positron emission tomography (PET). The 11 compounds were fluoropyridinyl derivatives labeled with the positron-emitter fluorine-18, [(18)F]F-A-85380 [2-[(18)F]fluoro-3-[2(S)-2 azetidinylmethoxy]pyridine], and 10 selected N-substituted-azetidinyl and pyrrolidinyl closely related [(18)F]fluoropyridinyl derivatives (including [N'-aromatic/aliphatic]-thioureas, -ureas, and -amides). The in vitro BBB model, a new coculture system of primary human brain endothelial cells and astrocytes, was used to measure the permeability coefficient for each compound. Dynamic PET studies were performed in rats with the same compounds, and a two-compartment model analysis was used to calculate their in vivo permeability coefficients. The 11 derivatives differed in their degree of BBB passage and transport mechanism. The analysis of PET data showed a significant cerebral uptake for six derivatives, for which the in vitro evaluation indicated active influx or free diffusion. Five derivatives displayed low in vivo cerebral uptake, in agreement with the observation of an in vitro active efflux. Overall, there was a remarkable correlation between the in vitro and in vivo permeability coefficients (r = 0.99). This double study proves a close correlationship between the assessment of the BBB passage in vitro and in vivo. The in vitro model of human BBB offers the possibility of subtle discrimination of various BBB permeability degrees and transport mechanisms. Conversely, small animal PET imaging appears suitable to screen directly in vivo brain targeting of drugs or radiopharmaceutical candidates.     

Preclinical In Vitro and In Vivo Characterization of Synaptic Vesicle 2A–Targeting Compounds Amenable to F-18 Labeling as Potential PET Radioligands for Imaging of Synapse Integrity

Molecular Imaging and Biology - Current synaptic vesicle 2A (SV2A) positron emission tomography (PET) imaging agents include the nanomolar affinity probes [11C]UCB-J and [18F]UCB-H derived from the...     

Nicotinic alpha4beta2 receptor binding in dementia with Lewy bodies using 123I-5IA-85380 SPECT demonstrates a link between occipital changes and visual hallucinations

INTRODUCTION: To investigate in vivo differences in the distribution of alpha4beta2 subtypes of nAChR using the ligand (123)I-5-Iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) and single photon emission computed tomography (SPECT) in DLB and similarly aged controls. METHODS: Thirty-one subjects (15 DLB and 16 controls) underwent (123)I-5IA-85380 and perfusion ((99m)Tc-exametazime) SPECT scanning. Patient scans were compared to scans of control subjects on a voxel-by-voxel basis using SPM2. RESULTS: Compared to controls, significant reductions in relative (123)I-5IA-85380 uptake were identified in frontal, striatal, temporal and cingulate regions in DLB. Elevation of scaled (123)I-5IA-85380 uptake in occipital cortex was observed in DLB relative to controls, as well as being associated with DLB subjects with a recent history of visual hallucinations. Changes in (123)I-5IA-85380 SPECT in DLB were different from perfusion. CONCLUSION: Reductions in normalised (123)I-5IA-85380 uptake in DLB were distinct from their perfusion deficits. Significant increase in occipital lobe uptake was present in DLB, a change most pronounced in subjects with a recent history of visual hallucinations. The findings directly link cholinergic changes in occipital lobe to visual hallucinations in DLB.     

Declines in different beta2* nicotinic receptor populations in monkey striatum after nigrostriatal damage

In the present study we used the nicotinic ligand 5-iodo-A-85380 [5-iodo-3(2(S)-azetidinylmethoxy)pyridine], which selectively binds to beta2-containing nicotinic acetylcholine receptors, to elucidate the nicotinic receptor subtypes affected by nigrostriatal damage in the monkey. Autoradiographic studies in control monkeys showed that 5-[(125)I]A-85380 ([(125)I]A-85380) binds throughout the brain with the characteristics of a nicotinic receptor ligand. Competition experiments with cytisine and nicotine yielded K(i) values of approximately 1 and 10 nM, respectively, with complete inhibition of [(125)I]A-85380 binding at a 10(-6) M concentration of these ligands. In contrast, alpha-conotoxin MII blocked radioligand binding in the striatum by 30% at the highest concentrations, suggesting that a subset of striatal [(125)I]A-85380 sites are alpha-conotoxin MII-sensitive. Monkeys treated with the nigrostriatal neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine showed a selective decrease in striatal [(125)I]A-85380 sites, with a 42% reduction in the caudate and putamen of animals with moderate nigrostriatal lesioning and a 53% decline in the striatum of severely lesioned animals. Our previous work had demonstrated that there were two populations of nicotinic receptors eliminated after nigrostriatal damage, an alpha-conotoxin MII-sensitive and an alpha-conotoxin MII- resistant subtype. Analysis of both striatal [(125)I]A-85380 and [(125)I]epibatidine competition studies extend our earlier studies by demonstrating that the alpha-conotoxin MII-sensitive sites eliminated after moderate nigrostriatal lesioning appear to be composed of two nicotinic receptor subtypes. The data may be important for potential therapeutic approaches because they suggest that there are at least three populations of nicotinic receptors in monkey striatum, of which two are selectively vulnerable to nigrostriatal damage, while the third is more resistant.     

Feasibility of 2–deoxy–2–[18F]fluoro–D–glucose– A85380–PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo

Summary Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (α₄β₂) nicotinic acetylcholine receptor PET ligand (2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinson's disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2–deoxy–2–[¹⁸F]fluoro–D–glucose–A85380 PET–imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 whole body PET–scans were performed on a Siemens PET/CT biograph^TM 75.4 min±6.7 after i.v. injection of 371.2±58.1 MBq. Average count rate density of left ventricle ROI's and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart–to–lung ratios were calculated in each volunteer and patient. Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart–to–lung ratios in the volunteer group were not different from patients suffering from Parkinson's disease or MSA (3.2 ± 0.5 vs 3.2 ± 0.8 and 2.96±0.7, mean ± SD), respectively. Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 PET scans both in cardiac–healthy subjects and patients suffering from Parkinson's disease or multiple system atrophy. The heart– as well as the lung–tracer uptake was almost constant throughout all subjects leading to a good targetto– background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors. An erratum to this article is available at .     

Preparation,in vitro and in vivo evaluation,and molecular dynamics (MD) simulation studies of novel F-18 labeled tumor imaging agents targeting focal adhesion kinase (FAK)

Focal adhesion kinase (FAK) has been identified as a promising target in the early diagnosis and therapy of tumor. In this work, we obtained and evaluated another two novel pyrimidine-based F-18 labeled tumor imaging agents targeting FAK. Among them, the corresponding F-19 standards [¹⁹F]2, displayed inhibition of FAK with IC₅₀ values of 57.1 nM (better than the results in our published work) and showed an good selectivity profile against some other kinds of cancer-related kinases. [¹⁸F]2 also had relatively good results in the in vivo biodistribution in S180-tumor-bearing mice, with tumor uptake of 5.40 ± 0.12 and 5.96 ± 0.09 % ID per g at 15 and 30 min post-injection, respectively. What''s more, [¹⁸F]2 could be accumulated in tumor at 30 min post-injection, which could be observed from the coronal micro-PET images of mice bearing S180 tumor. In addition, the blocking study for the [¹⁸F]2 with PF-562271 (one of the well-known best selective FAK inhibitor), displayed distinct reduction in the uptake of the radiotracer in tumor at 30 min post-injection in mice, suggesting that the uptake of [¹⁸F]2 in tumor was due to FAK over-expression or high expression in tumor. And the results of the molecular dynamics (MD) simulations and the docking studies were in consistent with the changing trends of the interaction between the F-19 standards and the FAK. Finally, in order to further increase the uptake of the F-18 labeled tracer in tumor, the following points should arouse attention, which could also be considered as the new findings and contributions of this study to the field of the tumor imaging agents: (1) the F-18 labeled tumor radiotracers which have closer interaction with the FAK, should be further designed, via building of models such as 3D-QSAR model to make reasonable guidance to our drug design and consideration of some functional groups which have hydrogen-bonding or salt-bridge interactions with key residues in the kinase domain of FAK; (2) the F-18 radiotracers with better pharmacokinetic properties should be designed, via building of dynamic drug absorption and distribution model in different tissues, to predict whether the molecules have ideal absorption in tumor and low uptake in non-target tissues. The relevant study is being undertaken.

Coronal micro-PET images of mice bearing S180 tumor at 30 min post-injection of [¹⁸F]2.     

[11C]-DPA-713 and [18F]-DPA-714 as New PET Tracers for TSPO: A Comparison with [11C]-(R)-PK11195 in a Rat Model of Herpes Encephalitis

Background  

Activation of microglia cells plays an important role in neurological diseases. Positron emission tomography (PET) with [¹¹C]-(R)-PK11195 has already been used to visualize activated microglia cells in neurological diseases. However, [¹¹C]-(R)-PK11195 may not possess the required sensitivity to visualize mild neuroinflammation. In this study, we evaluated the PET tracers [¹¹C]-DPA-713 and [¹⁸F]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis.