{"title":"简化和高可靠的自动化生产[18F]FSPG用于临床研究","authors":"Mai Lin, Robert T. Ta, H. Charles Manning","doi":"10.1186/s41181-023-00200-8","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>(S)-4-(3-<sup>18</sup>F-Fluoropropyl)-L-Glutamic Acid ([<sup>18</sup>F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc<sup>−</sup>), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of [<sup>18</sup>F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [<sup>18</sup>F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [<sup>18</sup>F]FSPG production are still lacking to further increase the utility and clinical adoption of this radiotracer. Herein, we report the optimized automated approaches to produce [<sup>18</sup>F]FSPG through two commercially available radiosynthesizers capable of supporting centralized and large-scale production for clinical use.</p><h3>Results</h3><p>Starting with activity levels of 60–85 GBq, the fully-automated process to produce [<sup>18</sup>F]FSPG took less than 45 min with average radiochemical yields of 22.56 ± 0.97% and 30.82 ± 1.60% (non-decay corrected) using TRACERlab™ FXFN and FASTlab™, respectively. The radiochemical purities were > 95% and the formulated [<sup>18</sup>F]FSPG solution was determined to be sterile and colorless with the pH of 6.5–7.5. No radiolysis of the product was observed up to 8 h after final batch formulation.</p><h3>Conclusions</h3><p>In summary, cGMP-compliant radiosyntheses and quality control of [<sup>18</sup>F]FSPG have been established on two commercially available synthesizers leveraging high activity concentration and radiochemical purity. While the clinical trials using [<sup>18</sup>F]FSPG PET are currently underway, the automated approaches reported herein will accelerate the clinical adoption of this radiotracer and warrant centralized and large-scale production of [<sup>18</sup>F]FSPG.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"8 1","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366059/pdf/","citationCount":"0","resultStr":"{\"title\":\"Simplified and highly-reliable automated production of [18F]FSPG for clinical studies\",\"authors\":\"Mai Lin, Robert T. Ta, H. Charles Manning\",\"doi\":\"10.1186/s41181-023-00200-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>(S)-4-(3-<sup>18</sup>F-Fluoropropyl)-L-Glutamic Acid ([<sup>18</sup>F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc<sup>−</sup>), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of [<sup>18</sup>F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [<sup>18</sup>F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [<sup>18</sup>F]FSPG production are still lacking to further increase the utility and clinical adoption of this radiotracer. Herein, we report the optimized automated approaches to produce [<sup>18</sup>F]FSPG through two commercially available radiosynthesizers capable of supporting centralized and large-scale production for clinical use.</p><h3>Results</h3><p>Starting with activity levels of 60–85 GBq, the fully-automated process to produce [<sup>18</sup>F]FSPG took less than 45 min with average radiochemical yields of 22.56 ± 0.97% and 30.82 ± 1.60% (non-decay corrected) using TRACERlab™ FXFN and FASTlab™, respectively. The radiochemical purities were > 95% and the formulated [<sup>18</sup>F]FSPG solution was determined to be sterile and colorless with the pH of 6.5–7.5. No radiolysis of the product was observed up to 8 h after final batch formulation.</p><h3>Conclusions</h3><p>In summary, cGMP-compliant radiosyntheses and quality control of [<sup>18</sup>F]FSPG have been established on two commercially available synthesizers leveraging high activity concentration and radiochemical purity. While the clinical trials using [<sup>18</sup>F]FSPG PET are currently underway, the automated approaches reported herein will accelerate the clinical adoption of this radiotracer and warrant centralized and large-scale production of [<sup>18</sup>F]FSPG.</p></div>\",\"PeriodicalId\":534,\"journal\":{\"name\":\"EJNMMI Radiopharmacy and Chemistry\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2023-07-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366059/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJNMMI Radiopharmacy and Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://link.springer.com/article/10.1186/s41181-023-00200-8\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJNMMI Radiopharmacy and Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1186/s41181-023-00200-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
引用次数: 0
摘要
(S)-4-(3-18F-氟丙基)- l -谷氨酸([18F]FSPG)是一种正电子发射断层扫描(PET)示踪剂，特异性靶向胱氨酸/谷氨酸反转运蛋白(xc−)，该蛋白在癌症和几种神经系统疾病中经常过表达。[18F]FSPG在健康志愿者中的剂量学和生物分布以及在非小细胞肺癌、肝细胞癌和脑肿瘤患者中的肿瘤检测的初步研究显示了令人鼓舞的结果。特别是，观察到脑、肺、肝和肠的低背景摄取，进一步导致[18F]FSPG PET具有良好的成像对比度。然而，对于[18F]FSPG的生产，仍然缺乏可靠的符合cgmp的自动化生产程序，以进一步提高该放射性示踪剂的实用性和临床应用。在此，我们报告了通过两种商用放射性合成器生产[18F]FSPG的优化自动化方法，这些合成器能够支持临床使用的集中和大规模生产。结果在活性水平为60-85 GBq时，使用TRACERlab™FXFN和FASTlab™生产[18F]FSPG的全自动过程耗时不到45分钟，平均放射化学产率分别为22.56±0.97%和30.82±1.60%(未校正衰变)。放射化学纯度为95%，经测定配制的[18F]FSPG溶液无菌无色，pH为6.5-7.5。在最终批制剂后8小时内未观察到产品的放射性溶解。综上所述，[18F]FSPG符合cgmp的放射性合成和质量控制已经在两种具有高活性浓度和放射化学纯度的市售合成器上建立起来。虽然使用[18F]FSPG PET的临床试验目前正在进行中，但本文报道的自动化方法将加速该放射性示踪剂的临床应用，并保证[18F]FSPG的集中和大规模生产。
Simplified and highly-reliable automated production of [18F]FSPG for clinical studies
Background
(S)-4-(3-18F-Fluoropropyl)-L-Glutamic Acid ([18F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc−), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of [18F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [18F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [18F]FSPG production are still lacking to further increase the utility and clinical adoption of this radiotracer. Herein, we report the optimized automated approaches to produce [18F]FSPG through two commercially available radiosynthesizers capable of supporting centralized and large-scale production for clinical use.
Results
Starting with activity levels of 60–85 GBq, the fully-automated process to produce [18F]FSPG took less than 45 min with average radiochemical yields of 22.56 ± 0.97% and 30.82 ± 1.60% (non-decay corrected) using TRACERlab™ FXFN and FASTlab™, respectively. The radiochemical purities were > 95% and the formulated [18F]FSPG solution was determined to be sterile and colorless with the pH of 6.5–7.5. No radiolysis of the product was observed up to 8 h after final batch formulation.
Conclusions
In summary, cGMP-compliant radiosyntheses and quality control of [18F]FSPG have been established on two commercially available synthesizers leveraging high activity concentration and radiochemical purity. While the clinical trials using [18F]FSPG PET are currently underway, the automated approaches reported herein will accelerate the clinical adoption of this radiotracer and warrant centralized and large-scale production of [18F]FSPG.
![Simplified and highly-reliable automated production of [18F]FSPG for clinical studies](https://img.booksci.cn/booksciimg/2023-7/202311057823523018658525857933.jpg)
![Simplified and highly-reliable automated production of [18F]FSPG for clinical studies](https://img.booksci.cn/booksciimg/2023-7/2023110578261912332065104991360.jpg)
![Simplified and highly-reliable automated production of [18F]FSPG for clinical studies](https://img.booksci.cn/booksciimg/2023-7/2023110578269937506005329183080.jpg)
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