ImmunoPET/CT imaging of clear cell renal cell carcinoma with [18F]RCCB6 : a first-in-human study
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
European journal of nuclear medicine and molecular imaging - (2024) vom: 14. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Qianyun [VerfasserIn] |
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| Links: |
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| Themen: |
CD70 |
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| Anmerkungen: |
Date Revised 14.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1007/s00259-024-06672-3 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369702530 |
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| 100 | 1 | |a Wu, Qianyun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ImmunoPET/CT imaging of clear cell renal cell carcinoma with [18F]RCCB6 |b a first-in-human study |
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| 520 | |a © 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CD70 | |
| 650 | 4 | |a ImmunoPET | |
| 650 | 4 | |a Molecular imaging | |
| 650 | 4 | |a Renal cell carcinoma | |
| 650 | 4 | |a Single-domain antibody | |
| 700 | 1 | |a Wu, Yanfei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, You |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Yihui |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jianjun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhai, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Weijun |e verfasserin |4 aut | |
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