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

doi:10.1007/s00259-024-06672-3

. 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 Zhang¹, Yihui Guan², Gang Huang¹, Fang Xie², Jianjun Liu³, Wei Zhai⁴, Weijun Wei⁵

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.
² Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China.
³ Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China. nuclearj@163.com.
⁴ Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China. jacky_zw2002@hotmail.com.
⁵ Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China. wwei@shsmu.edu.cn.

^# Contributed equally.

PMID: 38480552
DOI: 10.1007/s00259-024-06672-3

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.

. 2024 Jul;51(8):2444-2457.

doi: 10.1007/s00259-024-06672-3. Epub 2024 Mar 14.

Authors

Qianyun Wu^#¹, Yanfei Wu^#², You Zhang¹, Yihui Guan², Gang Huang¹, Fang Xie², Jianjun Liu³, Wei Zhai⁴, Weijun Wei⁵

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.
² Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China.
³ Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China. nuclearj@163.com.
⁴ Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China. jacky_zw2002@hotmail.com.
⁵ Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China. wwei@shsmu.edu.cn.

^# Contributed equally.

PMID: 38480552
DOI: 10.1007/s00259-024-06672-3

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

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[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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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

[8] 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

[9] 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

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

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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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