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ImmunoPET/CT imaging of clear cell renal cell carcinoma with [18F]RCCB6: a first-in-human study

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Abstract

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.

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Data availability

All the relevant data are available from Prof. W. Wei on rational request.

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Funding

This work was supported in part by the National Key Research and Development Program of China (Grant No. 2020YFA0909000), the National Natural Science Foundation of China (Grant No. 82372014), and the Shen Kang-United Imaging Joint Research and Development Plan (Grant No. SKLY2022CRT301).

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Author notes

  1. Qianyun Wu and Yanfei Wu contributed equally to the work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Qianyun Wu, You Zhang, Gang Huang, Jianjun Liu & Weijun Wei

  2. Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Yanfei Wu, Yihui Guan & Fang Xie

  3. Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Wei Zhai

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Contributions

W. Wei, W. Zhai and J. Liu conceptualised and designed the study methodology. Q. Wu, Y. Zhang, and Y. Wu conducted experiments and performed visualisation work. J. Liu, G. Huang, and Y. Guan were responsible for project administration and supervised the study. W. Wei, Q. Wu, and Y. Wu wrote the original manuscript draft, while others contributed to the writing. W. Wei and W. Zhai reviewed, edited, and finalised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jianjun Liu, Wei Zhai or Weijun Wei.

Ethics declarations

Ethics approval

All animal imaging studies were approved by the Institutional Committee for the Care and Use of Animals (Renji Hospital, Shanghai Jiao Tong University School of Medicine). The clinical study was approved by the Institutional Ethical Reviewing Board of Huashan Hospital and registered as a prospective clinical trial (ClinicalTrials.gov ID NCT06148220).

Consent to participate

Written informed consents were obtained from all the included patients.

Consent to publish

All the participants agreed to the publication of the imaging data.

Competing interests

W. Wei is a consultant of Alpha Nuclide (Ningbo) Medical Technology Co., Ltd. W. Wei, Q. Wu, and J. Liu are co-inventors of three pending patents describing the disclosed imaging technologies.

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Wu, Q., Wu, Y., Zhang, Y. et al. ImmunoPET/CT imaging of clear cell renal cell carcinoma with [18F]RCCB6: a first-in-human study. Eur J Nucl Med Mol Imaging 51, 2444–2457 (2024). https://doi.org/10.1007/s00259-024-06672-3

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