{"title":"作为 HER2 肿瘤成像的新型分子探针,[18F]AlF-RESCA-5F7 的放射合成和临床前评估。","authors":"Ruhua Tian, Jinping Kong, Yingfang He, Guoqiang Xu, Tengxiang Chen, Junbin Han","doi":"10.62347/BVPK1360","DOIUrl":null,"url":null,"abstract":"<p><p>HER2 overexpression is associated with various tumor types and prompted the development of targeted therapies. Previously, <i>iso</i>-[<sup>211</sup>At]SGMAB-5F7 was developed as a HER2-targeted alpha therapy agent, demonstrating promising therapeutic efficacy in the preclinical stage. Aiming for an <sup>18</sup>F-labeled tracer for companion diagnostics in clinical translation, we employed the Al<sup>18</sup>F-RESCA strategy in our current work and investigated whether [<sup>18</sup>F]AlF-RESCA-5F7 could visualize HER2 expression <i>in vivo</i>. [<sup>18</sup>F]AlF-RESCA-5F7 was attained with high radiochemical purity (> 99%) and molar activity in the range of 16.5 ± 8.8 GBq/μmol (n = 8). Compared to previously reported radiotracers that contained 5F7 as the HER2-targeting carrier and fluorine-18 as the positron-emitting isotope, the radiosynthesis was simplified to one single step within 30 min. The dissociation constant of [<sup>18</sup>F]AlF-RESCA-5F7 was determined as 3.3 nM <i>via</i> saturation binding assay using SKOV3 ovarian carcinoma cells. Tumor uptake of the novel tracer in Balb/c nude mice bearing SKOV3 xenografts was 4.69 ± 1.51, 3.34 ± 0.82 and 3.77 ± 0.99 %ID/g at 1, 2, and 4 h post-injection. Even though high retention of radioactivity was seen in the kidneys, micro-PET/CT imaging of [<sup>18</sup>F]AlF-RESCA-5F7 delineated the tumor up to 4 h post-injection with minimal activity in the gallbladder, intestines, and bone. This study suggests that [<sup>18</sup>F]AlF-RESCA-5F7 is a promising HER2 PET radiotracer with an eased radiolabeling method. Whether [<sup>18</sup>F]AlF-RESCA-5F7 could work as a companion diagnostic agent to assist in patient stratification and treatment monitoring of <i>iso</i>-[<sup>211</sup>At]SGMAB-5F7 warrants further investigation.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253080/pdf/","citationCount":"0","resultStr":"{\"title\":\"Radiosynthesis and preclinical evaluations of [<sup>18</sup>F]AlF-RESCA-5F7 as a novel molecular probe for HER2 tumor imaging.\",\"authors\":\"Ruhua Tian, Jinping Kong, Yingfang He, Guoqiang Xu, Tengxiang Chen, Junbin Han\",\"doi\":\"10.62347/BVPK1360\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>HER2 overexpression is associated with various tumor types and prompted the development of targeted therapies. Previously, <i>iso</i>-[<sup>211</sup>At]SGMAB-5F7 was developed as a HER2-targeted alpha therapy agent, demonstrating promising therapeutic efficacy in the preclinical stage. Aiming for an <sup>18</sup>F-labeled tracer for companion diagnostics in clinical translation, we employed the Al<sup>18</sup>F-RESCA strategy in our current work and investigated whether [<sup>18</sup>F]AlF-RESCA-5F7 could visualize HER2 expression <i>in vivo</i>. [<sup>18</sup>F]AlF-RESCA-5F7 was attained with high radiochemical purity (> 99%) and molar activity in the range of 16.5 ± 8.8 GBq/μmol (n = 8). Compared to previously reported radiotracers that contained 5F7 as the HER2-targeting carrier and fluorine-18 as the positron-emitting isotope, the radiosynthesis was simplified to one single step within 30 min. The dissociation constant of [<sup>18</sup>F]AlF-RESCA-5F7 was determined as 3.3 nM <i>via</i> saturation binding assay using SKOV3 ovarian carcinoma cells. Tumor uptake of the novel tracer in Balb/c nude mice bearing SKOV3 xenografts was 4.69 ± 1.51, 3.34 ± 0.82 and 3.77 ± 0.99 %ID/g at 1, 2, and 4 h post-injection. Even though high retention of radioactivity was seen in the kidneys, micro-PET/CT imaging of [<sup>18</sup>F]AlF-RESCA-5F7 delineated the tumor up to 4 h post-injection with minimal activity in the gallbladder, intestines, and bone. This study suggests that [<sup>18</sup>F]AlF-RESCA-5F7 is a promising HER2 PET radiotracer with an eased radiolabeling method. Whether [<sup>18</sup>F]AlF-RESCA-5F7 could work as a companion diagnostic agent to assist in patient stratification and treatment monitoring of <i>iso</i>-[<sup>211</sup>At]SGMAB-5F7 warrants further investigation.</p>\",\"PeriodicalId\":7572,\"journal\":{\"name\":\"American journal of nuclear medicine and molecular imaging\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-06-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253080/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of nuclear medicine and molecular imaging\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.62347/BVPK1360\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of nuclear medicine and molecular imaging","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.62347/BVPK1360","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Radiosynthesis and preclinical evaluations of [18F]AlF-RESCA-5F7 as a novel molecular probe for HER2 tumor imaging.
HER2 overexpression is associated with various tumor types and prompted the development of targeted therapies. Previously, iso-[211At]SGMAB-5F7 was developed as a HER2-targeted alpha therapy agent, demonstrating promising therapeutic efficacy in the preclinical stage. Aiming for an 18F-labeled tracer for companion diagnostics in clinical translation, we employed the Al18F-RESCA strategy in our current work and investigated whether [18F]AlF-RESCA-5F7 could visualize HER2 expression in vivo. [18F]AlF-RESCA-5F7 was attained with high radiochemical purity (> 99%) and molar activity in the range of 16.5 ± 8.8 GBq/μmol (n = 8). Compared to previously reported radiotracers that contained 5F7 as the HER2-targeting carrier and fluorine-18 as the positron-emitting isotope, the radiosynthesis was simplified to one single step within 30 min. The dissociation constant of [18F]AlF-RESCA-5F7 was determined as 3.3 nM via saturation binding assay using SKOV3 ovarian carcinoma cells. Tumor uptake of the novel tracer in Balb/c nude mice bearing SKOV3 xenografts was 4.69 ± 1.51, 3.34 ± 0.82 and 3.77 ± 0.99 %ID/g at 1, 2, and 4 h post-injection. Even though high retention of radioactivity was seen in the kidneys, micro-PET/CT imaging of [18F]AlF-RESCA-5F7 delineated the tumor up to 4 h post-injection with minimal activity in the gallbladder, intestines, and bone. This study suggests that [18F]AlF-RESCA-5F7 is a promising HER2 PET radiotracer with an eased radiolabeling method. Whether [18F]AlF-RESCA-5F7 could work as a companion diagnostic agent to assist in patient stratification and treatment monitoring of iso-[211At]SGMAB-5F7 warrants further investigation.
期刊介绍:
The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.