Purpose: Radiolabeled heterodimeric peptide has emerged as a highly promising targeting strategy for PET imaging due to their superior properties. RGD and GE11 are two peptides binding to receptor integrin alpha(v)beta(3) and EGFR, respectively, which both overexpress in many different types of tumors. This study focuses on the synthesis and evaluation of a RGD and GE11-containing heterodimeric radiotracer [Cu-64]Cu-NOTA-RGD-GE11 for PET imaging of tumors that simultaneously overexpress integrin alpha(v)beta(3) and EGFR. Procedures: [Cu-64]Cu-NOTA-RGD-GE11 was prepared by the conjugation of RGD-PEG4-NOTA-N-3 and GE11PEG4-BCN via metal-free click chemistry, followed by radiolabeling with 64Cu. Cell uptake and efflux studies, saturation binding assay, the animal PET/CT and biodistribution studies were conducted to characterize the biological properties of [Cu-64]Cu-NOTA-RGD-GE11. Results: [Cu-64]Cu-NOTA-RGD-GE11 was synthesized with a radiochemical purity of >97 % and molar activity of 23 GBq/mu mol at the end of synthesis. [Cu-64]Cu-NOTA-RGD-GE11 showed moderate hydrophilicity, good stability in mouse serum and high specific uptake by the human pancreatic cancer cell line (BxPC3) in the in vitro studies. Compared to the two monomeric counterparts [Cu-64]Cu-NOTA-RGD and [Cu-64]Cu-NOTA-GE11, [Cu-64]CuNOTA-RGD-GE11 demonstrated significantly improved tumor uptakes (e.g. 4.63 +/- 0.25 %ID/g vs 1.24 +/- 0.18 % ID/g and 0.77 +/- 0.13 %ID/g, 2 h after injection, p < 0.05) in the subsequent in vivo evaluation in mice bearing BxPC3 xenograft. Tumor uptake could be blocked in the presence of both non-radioactive c(RGDyK) and GE11 peptides, indicating good tumor specificity of [Cu-64]Cu-NOTA-RGD-GE11 in vivo. Conclusion: The results suggested that the as-developed [Cu-64]Cu-NOTA-RGD-GE11 could serve as a potential PET tracer for the noninvasive imaging of integrin alpha(v)beta(3) and EGFR expression in tumors.

目的 探讨注射半剂量18F-氟代脱氧葡糖(18F-flurodeoxyglucose,18F-FDG)对恶性肿瘤患者全身正电子发射计算机断层显像(positron emission tomography/computed tomography,PET/CT)图像质量的影响,以确定注射半剂量18F-FDG对恶性肿瘤进行有效诊断的可行性.方法 回顾性分析2021年2月至2021年9月在河南省人民医院PET/CT中心18F-FDG全身显像40例确诊恶性肿瘤患者的PET/CT图像.患者分为全剂量组(3.70 MBq/kg,20例)和半剂量组(1.85 MBq/kg,20例).两组患者均采用联影全景动态PET/CT扫描仪采集图像,全剂量组患者PET采集时间3 min,半剂量组患者PET采集时间10 min.由2名从业核医学5年以上的医生采用5分制(5分-优;1分-差)对两组图像打分,并对比两组肿瘤部位最大标准摄取值(maximum of the stand-ard uptake value,SUVmax)值、肿瘤与肌肉摄取比值等指标,以评定图像质量,数据分析采用x2检验.结果 全剂量组和半剂量组图像在性别、年龄、体质量指数、注射和成像间隔时间、肿瘤病变性质和病理类型等方面两组之间差异无统计学意义(P＞0.05).全剂量组和半剂量组图像质量平均评分接近,分别为(4.6±0.3)分和(4.5±0.2)分.两组肿瘤SUVmax和肿瘤与肌肉摄取比值等指标之间没有显著差异(P＞0.05).结论 与全剂量组相比,半剂量组呈现了较好的信噪比.半剂量组获得的图像质量评分与全剂量组相比没有统计学意义上的差异.因此,患者在接受联影全景动态PET/CT检查时,如果18F-FDG的总剂量有限,患者可通过注射半剂量的18F-FDG并适当延长PET采集时间来满足临床诊断对图像的要求.

Objective:To prepare 68Ga-2-(4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)pentanedioic acid (NODAGA)-YHWYGYTPQNVI (GE11) and evaluate its feasibility of PET imaging for pancreatic cancer. Methods:GE11 peptide was conjugated with NODAGA and then labeled with 68Ga. The labeling yield, radiochemical purity, hydrophilicity, stability and specificity in vitro were determined. Human pancreatic cancer BxPC3 nude mice models ( n=9) were established. MicroPET imaging was then obtained after 30 and 90 min, and mice were sacrificed at 90 min to acquire the radioactivity distribution of main organs and tumors. Pair t test was used to analyze the data. Results:The labeling yield was (73.5±5.4)% and radiochemical purity was more than 98%. After incubation 120 min in mouse serum at 37 ℃, radiochemical purity was more than 92%. The uptake was specific in BxPC3 cell lines. MicroPET images showed that 68Ga-NODAGA-GE11 could accumulate quickly in tumor. Value of tumor uptake was significantly higher than that of normal pancreas at 90 min ((1.38±0.25) vs (0.49±0.07) %ID/g; t=12.67, P<0.05), and the radio-uptake of blood, muscle and bone was lower than that of tumor. Conclusions:68Ga-NODAGA-GE11 is easy to be prepared with high radiochemical purity and good stability, and can specifically target BxPC3 xenograft tumor. However, due to the high uptake in the kidneys and liver, the value of 68Ga-NODAGA-GE11 in PET imaging for pancreatic tumor needs further study.

A fully automated synthesis of 11C-labeled N-[2-[4-(2-methoxyphenyl)-l-piperazinyl] ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate (11C-WAY-100635) for imaging 5-HT1A receptors was performed on a module system.11C-WAY-100635 was obtained based on the methylation reaction of the precursor (O-demethyl)-WAY-100635,purification with HPLC and subsequent removal of organic solvents using a Sep-Pak Plus C18.The results revealed that fully automated synthesis of 11C-WAY-100635 was completed within the total synthesis time of about 40 min.The uncorrected radiochemical yield was between 10％ and 20％,and the radiochemical purity was over 97％.After the intravenous injection of11C-WAY-100635 (about 111 MBq),the uptake in the brain tissues of the white rabbit was significantly higher than the other tissues of head.This method provides simple synthesis of 11C-WAY-100635 with relatively short radiosynthesis time and a high radiochemical yield for clinical need.