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. 2024 Jul;51(8):2444-2457.
doi: 10.1007/s00259-024-06672-3. Epub 2024 Mar 14.

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

Qianyun Wu #  1 , Yanfei Wu #  2 , You Zhang  1 , Yihui Guan  2 , Gang Huang  1 , Fang Xie  2 , Jianjun Liu  3 , Wei Zhai  4 , Weijun Wei  5
Affiliations

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

Qianyun Wu et al. Eur J Nucl Med Mol Imaging. 2024 Jul.

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.

Keywords: CD70; ImmunoPET; Molecular imaging; Renal cell carcinoma; Single-domain antibody.

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References

    1. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of tumours of the urinary system and male genital organs—part a: renal, penile, and testicular tumours. European Urol. 2016;70:93–105. https://doi.org/10.1016/j.eururo.2016.02.029 . - DOI
    1. Dabestani S, Thorstenson A, Lindblad P, Harmenberg U, Ljungberg B, Lundstam S. Renal cell carcinoma recurrences and metastases in primary non-metastatic patients: a population-based study. World J Urol. 2016;34:1081–6. https://doi.org/10.1007/s00345-016-1773-y . - DOI - PubMed
    1. Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30:706–20. https://doi.org/10.1093/annonc/mdz056 . - DOI - PubMed
    1. Roussel E, Capitanio U, Kutikov A, Oosterwijk E, Pedrosa I, Rowe SP, et al. Novel imaging methods for renal mass characterization: a collaborative review. European Urol. 2022;81:476–88. https://doi.org/10.1016/j.eururo.2022.01.040 . - DOI
    1. James ML, Gambhir SS. A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012;92:897–965. https://doi.org/10.1152/physrev.00049.2010 . - DOI - PubMed

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