{"title":"用于 PET 成像的新型叶酸受体靶向示踪剂 [18F]AlF-NOTA-Asp2-PEG2-Folate 的合成与临床前评估。","authors":"Haoran Liang, Zihao Chen, Chunwei Mo, Ganghua Tang","doi":"10.1002/jlcr.4118","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Recently, the folate receptor (FR) has become an exciting target for the diagnosis of FR-positive malignancies. Nevertheless, suboptimal in vivo pharmacokinetic properties, particularly high uptake in the renal and hepatobiliary systems, are important limiting factors for the clinical translation of most FR-based radiotracers. In this study, we developed a novel <sup>18</sup>F-labeled FR-targeted positron emission tomography (PET) tracer [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate modified with a hydrophilic linker (−Asp<sub>2</sub>-PEG<sub>2</sub>) to optimize its pharmacokinetic properties and conducted a comprehensive preclinical assessment. The [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate was manually synthesized within 30 min with a non-decay-corrected radiochemical yield of 16.3 ± 2.0% (<i>n</i> = 5). Among KB cells, [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate exhibited high specificity and affinity for FR. PET/CT imaging and biodistribution experiments in KB tumor-bearing mice showed decent tumor uptake (1.7 ± 0.3% ID/g) and significantly decreased uptake in kidneys and liver (22.2 ± 2.1 and 0.3 ± 0.1% ID/g at 60 min p.i., respectively) of [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate, compared to the known tracer [<sup>18</sup>F]AlF-NOTA-Folate (78.6 ± 5.1 and 5.3 ± 0.5 % ID/g at 90 min p.i., respectively). The favorable properties of [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate, including its efficient synthesis, decent tumor uptake, relatively low renal uptake, and rapid clearance from most normal organs, portray it as a promising PET tracer for FR-positive tumors.</p>\n </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 10","pages":"334-340"},"PeriodicalIF":0.9000,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and Preclinical Evaluation of [18F]AlF-NOTA-Asp2-PEG2-Folate as a Novel Folate-Receptor-Targeted Tracer for PET Imaging\",\"authors\":\"Haoran Liang, Zihao Chen, Chunwei Mo, Ganghua Tang\",\"doi\":\"10.1002/jlcr.4118\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Recently, the folate receptor (FR) has become an exciting target for the diagnosis of FR-positive malignancies. Nevertheless, suboptimal in vivo pharmacokinetic properties, particularly high uptake in the renal and hepatobiliary systems, are important limiting factors for the clinical translation of most FR-based radiotracers. In this study, we developed a novel <sup>18</sup>F-labeled FR-targeted positron emission tomography (PET) tracer [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate modified with a hydrophilic linker (−Asp<sub>2</sub>-PEG<sub>2</sub>) to optimize its pharmacokinetic properties and conducted a comprehensive preclinical assessment. The [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate was manually synthesized within 30 min with a non-decay-corrected radiochemical yield of 16.3 ± 2.0% (<i>n</i> = 5). Among KB cells, [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate exhibited high specificity and affinity for FR. PET/CT imaging and biodistribution experiments in KB tumor-bearing mice showed decent tumor uptake (1.7 ± 0.3% ID/g) and significantly decreased uptake in kidneys and liver (22.2 ± 2.1 and 0.3 ± 0.1% ID/g at 60 min p.i., respectively) of [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate, compared to the known tracer [<sup>18</sup>F]AlF-NOTA-Folate (78.6 ± 5.1 and 5.3 ± 0.5 % ID/g at 90 min p.i., respectively). The favorable properties of [<sup>18</sup>F]AlF-NOTA-Asp<sub>2</sub>-PEG<sub>2</sub>-Folate, including its efficient synthesis, decent tumor uptake, relatively low renal uptake, and rapid clearance from most normal organs, portray it as a promising PET tracer for FR-positive tumors.</p>\\n </div>\",\"PeriodicalId\":16288,\"journal\":{\"name\":\"Journal of labelled compounds & radiopharmaceuticals\",\"volume\":\"67 10\",\"pages\":\"334-340\"},\"PeriodicalIF\":0.9000,\"publicationDate\":\"2024-07-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of labelled compounds & radiopharmaceuticals\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jlcr.4118\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of labelled compounds & radiopharmaceuticals","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jlcr.4118","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Synthesis and Preclinical Evaluation of [18F]AlF-NOTA-Asp2-PEG2-Folate as a Novel Folate-Receptor-Targeted Tracer for PET Imaging
Recently, the folate receptor (FR) has become an exciting target for the diagnosis of FR-positive malignancies. Nevertheless, suboptimal in vivo pharmacokinetic properties, particularly high uptake in the renal and hepatobiliary systems, are important limiting factors for the clinical translation of most FR-based radiotracers. In this study, we developed a novel 18F-labeled FR-targeted positron emission tomography (PET) tracer [18F]AlF-NOTA-Asp2-PEG2-Folate modified with a hydrophilic linker (−Asp2-PEG2) to optimize its pharmacokinetic properties and conducted a comprehensive preclinical assessment. The [18F]AlF-NOTA-Asp2-PEG2-Folate was manually synthesized within 30 min with a non-decay-corrected radiochemical yield of 16.3 ± 2.0% (n = 5). Among KB cells, [18F]AlF-NOTA-Asp2-PEG2-Folate exhibited high specificity and affinity for FR. PET/CT imaging and biodistribution experiments in KB tumor-bearing mice showed decent tumor uptake (1.7 ± 0.3% ID/g) and significantly decreased uptake in kidneys and liver (22.2 ± 2.1 and 0.3 ± 0.1% ID/g at 60 min p.i., respectively) of [18F]AlF-NOTA-Asp2-PEG2-Folate, compared to the known tracer [18F]AlF-NOTA-Folate (78.6 ± 5.1 and 5.3 ± 0.5 % ID/g at 90 min p.i., respectively). The favorable properties of [18F]AlF-NOTA-Asp2-PEG2-Folate, including its efficient synthesis, decent tumor uptake, relatively low renal uptake, and rapid clearance from most normal organs, portray it as a promising PET tracer for FR-positive tumors.
期刊介绍：
The Journal of Labelled Compounds and Radiopharmaceuticals publishes all aspects of research dealing with labeled compound preparation and applications of these compounds. This includes tracer methods used in medical, pharmacological, biological, biochemical and chemical research in vitro and in vivo.
The Journal of Labelled Compounds and Radiopharmaceuticals devotes particular attention to biomedical research, diagnostic and therapeutic applications of radiopharmaceuticals, covering all stages of development from basic metabolic research and technological development to preclinical and clinical studies based on physically and chemically well characterized molecular structures, coordination compounds and nano-particles.
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