Qianyun Wu, Yanfei Wu, You Zhang, Yihui Guan, Gang Huang, Fang Xie, Jianjun Liu, Wei Zhai, Weijun Wei
{"title":"用[18F]RCCB6对透明细胞肾细胞癌进行免疫PET/CT成像：首次人体研究。","authors":"Qianyun Wu, Yanfei Wu, You Zhang, Yihui Guan, Gang Huang, Fang Xie, Jianjun Liu, Wei Zhai, Weijun Wei","doi":"10.1007/s00259-024-06672-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The cluster of differentiation (CD70) is a potential biomarker of clear cell renal cell carcinoma (ccRCC). This study aims to develop CD70-targeted immuno-positron emission tomography/computed tomography (immunoPET/CT) imaging tracers and explore the diagnostic value in preclinical studies and the potential value in detecting metastases in ccRCC patients.</p><p><strong>Methods: </strong>Four novel CD70-specific single-domain antibodies (sdAbs) were produced and labelled with <sup>18</sup>F by the aluminium fluoride restrained complexing agent (AlF-RESCA) method to develop radiotracers. The visualisation properties of the tracers were evaluated in a subcutaneous ccRCC patient-derived xenograft (PDX) model. In a registered prospective clinical trial (NCT06148220), six patients with pathologically confirmed RCC were included and underwent immunoPET/CT examination exploiting one of the developed tracers (i.e., [<sup>18</sup>F]RCCB6).</p><p><strong>Results: </strong>We engineered four sdAbs (His-tagged RCCB3 and RCCB6, His-tag-free RB3 and RB6) specifically targeting recombinant human CD70 without cross-reactivity to murine CD70. ImmunoPET/CT imaging with [<sup>18</sup>F]RCCB3 and [<sup>18</sup>F]RCCB6 demonstrated a high tumour-to-background ratio in a subcutaneous ccRCC PDX model, with the latter showing better diagnostic potential supported by higher tumour uptake and lower bone accumulation. In comparison, [<sup>18</sup>F]RB6, developed by sequence optimisation, has significantly lower kidney accumulation than that of [<sup>18</sup>F]RCCB6. In a pilot translational study, [<sup>18</sup>F]RCCB6 immunoPET/CT displayed ccRCC metastases in multiple patients and demonstrated improved imaging contrast and diagnostic value than <sup>18</sup>F-FDG PET/CT in a patient with ccRCC.</p><p><strong>Conclusion: </strong>The work successfully developed a series of CD70-targeted immunoPET/CT imaging tracers. Of them, [<sup>18</sup>F]RCCB6 clearly and specifically identified inoculated ccRCCs in preclinical studies. Clinical translation of [<sup>18</sup>F]RCCB6 suggests potential for identifying recurrence and/or metastasis in ccRCC patients.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ImmunoPET/CT imaging of clear cell renal cell carcinoma with [<sup>18</sup>F]RCCB6: a first-in-human study.\",\"authors\":\"Qianyun Wu, Yanfei Wu, You Zhang, Yihui Guan, Gang Huang, Fang Xie, Jianjun Liu, Wei Zhai, Weijun Wei\",\"doi\":\"10.1007/s00259-024-06672-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The cluster of differentiation (CD70) is a potential biomarker of clear cell renal cell carcinoma (ccRCC). This study aims to develop CD70-targeted immuno-positron emission tomography/computed tomography (immunoPET/CT) imaging tracers and explore the diagnostic value in preclinical studies and the potential value in detecting metastases in ccRCC patients.</p><p><strong>Methods: </strong>Four novel CD70-specific single-domain antibodies (sdAbs) were produced and labelled with <sup>18</sup>F by the aluminium fluoride restrained complexing agent (AlF-RESCA) method to develop radiotracers. The visualisation properties of the tracers were evaluated in a subcutaneous ccRCC patient-derived xenograft (PDX) model. In a registered prospective clinical trial (NCT06148220), six patients with pathologically confirmed RCC were included and underwent immunoPET/CT examination exploiting one of the developed tracers (i.e., [<sup>18</sup>F]RCCB6).</p><p><strong>Results: </strong>We engineered four sdAbs (His-tagged RCCB3 and RCCB6, His-tag-free RB3 and RB6) specifically targeting recombinant human CD70 without cross-reactivity to murine CD70. ImmunoPET/CT imaging with [<sup>18</sup>F]RCCB3 and [<sup>18</sup>F]RCCB6 demonstrated a high tumour-to-background ratio in a subcutaneous ccRCC PDX model, with the latter showing better diagnostic potential supported by higher tumour uptake and lower bone accumulation. In comparison, [<sup>18</sup>F]RB6, developed by sequence optimisation, has significantly lower kidney accumulation than that of [<sup>18</sup>F]RCCB6. In a pilot translational study, [<sup>18</sup>F]RCCB6 immunoPET/CT displayed ccRCC metastases in multiple patients and demonstrated improved imaging contrast and diagnostic value than <sup>18</sup>F-FDG PET/CT in a patient with ccRCC.</p><p><strong>Conclusion: </strong>The work successfully developed a series of CD70-targeted immunoPET/CT imaging tracers. Of them, [<sup>18</sup>F]RCCB6 clearly and specifically identified inoculated ccRCCs in preclinical studies. Clinical translation of [<sup>18</sup>F]RCCB6 suggests potential for identifying recurrence and/or metastasis in ccRCC patients.</p>\",\"PeriodicalId\":11909,\"journal\":{\"name\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00259-024-06672-3\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nuclear Medicine and Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00259-024-06672-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/14 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
ImmunoPET/CT imaging of clear cell renal cell carcinoma with [18F]RCCB6: a first-in-human study.
Purpose: The cluster of differentiation (CD70) is a potential biomarker of clear cell renal cell carcinoma (ccRCC). This study aims to develop CD70-targeted immuno-positron emission tomography/computed tomography (immunoPET/CT) imaging tracers and explore the diagnostic value in preclinical studies and the potential value in detecting metastases in ccRCC patients.
Methods: Four novel CD70-specific single-domain antibodies (sdAbs) were produced and labelled with 18F by the aluminium fluoride restrained complexing agent (AlF-RESCA) method to develop radiotracers. The visualisation properties of the tracers were evaluated in a subcutaneous ccRCC patient-derived xenograft (PDX) model. In a registered prospective clinical trial (NCT06148220), six patients with pathologically confirmed RCC were included and underwent immunoPET/CT examination exploiting one of the developed tracers (i.e., [18F]RCCB6).
Results: We engineered four sdAbs (His-tagged RCCB3 and RCCB6, His-tag-free RB3 and RB6) specifically targeting recombinant human CD70 without cross-reactivity to murine CD70. ImmunoPET/CT imaging with [18F]RCCB3 and [18F]RCCB6 demonstrated a high tumour-to-background ratio in a subcutaneous ccRCC PDX model, with the latter showing better diagnostic potential supported by higher tumour uptake and lower bone accumulation. In comparison, [18F]RB6, developed by sequence optimisation, has significantly lower kidney accumulation than that of [18F]RCCB6. In a pilot translational study, [18F]RCCB6 immunoPET/CT displayed ccRCC metastases in multiple patients and demonstrated improved imaging contrast and diagnostic value than 18F-FDG PET/CT in a patient with ccRCC.
Conclusion: The work successfully developed a series of CD70-targeted immunoPET/CT imaging tracers. Of them, [18F]RCCB6 clearly and specifically identified inoculated ccRCCs in preclinical studies. Clinical translation of [18F]RCCB6 suggests potential for identifying recurrence and/or metastasis in ccRCC patients.
期刊介绍：
The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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