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Molecular imaging of renal cell carcinomas: ready for prime time

Abstract

The clinical diagnosis of renal cell carcinoma (RCC) is constantly evolving. Diagnostic imaging of RCC relying on enhanced computed tomography (CT) and magnetic resonance imaging (MRI) is commonly used for renal mass characterization and assessment of tumour thrombosis, whereas pathology is the gold standard for establishing diagnosis. However, molecular imaging is rapidly improving the clinical management of RCC, particularly clear-cell RCC. Molecular imaging aids in the non-invasive visualization and characterization of specific biomarkers such as carbonic anhydrase IX and CD70 within the tumours, which help to assess tumour heterogeneity and status. Target-specific molecular imaging of RCCs will substantially improve the diagnostic landscape of RCC and will further facilitate clinical decision-making regarding initial staging and re-staging, monitoring of recurrence and metastasis, patient stratification and selection, and the prediction and evaluation of treatment responses.

Key points

  • Metabolic imaging detects proliferation and metabolic heterogeneity in renal cell carcinoma (RCC).

  • 99mTc-sestamibi single-photon emission computed tomography–can help to identify benign and malignant renal masses.

  • Carbonic anhydrase IX is an established biomarker for clear-cell renal cell carcinoma (ccRCC), and the value of agents targeting this marker is being investigated in clinical settings.

  • CD70 is an emerging biomarker for ccRCC, and preliminary evidence suggests the unique value of CD70-targeted tracers in ccRCC imaging and of chimeric antigen receptor T cells in treating metastatic ccRCC.

  • Molecular imaging tracers targeting angiogenesis or immune checkpoints might be useful in assessing treatment responses in RCC, but well-designed clinical trials are needed.

  • Therapeutic radiopharmaceuticals with improved therapeutic index and safety profiles targeting carbonic anhydrase IX and CD70 are needed to achieve target-specific theranostics.

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Fig. 1: Antibody-based radiopharmaceuticals targeting CA-IX.
Fig. 2: Small-molecule-based radiopharmaceuticals targeting CA-IX.
Fig. 3: Peptide-based radiopharmaceuticals targeting CA-IX.
Fig. 4 : PSMA PET–CT in renal cell carcinoma.
Fig. 5: CD70-targeted PET imaging of ccRCCs with [18F]RCCB6.

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Acknowledgements

The work was partly supported by the National Key Research and Development Program of China (grant no. 2020YFA0909000) and the National Natural Science Foundation of China (grant nos 82372014 and 82402322).

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W.W., Q.W., J.C. and J.L. researched data for the article. All authors contributed substantially to discussion of the content. All authors wrote the article. W.W., Q.W., J.C. and J.L. reviewed and/or edited the manuscript before submission.

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Correspondence to Jianjun Liu, Jeremie Calais or Weijun Wei.

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W.W. is a consultant of Alpha Nuclide (Ningbo) Medical Technology Co., Ltd. The other authors declare no competing interests.

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Wu, Q., Shao, H., Zhai, W. et al. Molecular imaging of renal cell carcinomas: ready for prime time. Nat Rev Urol 22, 336–353 (2025). https://doi.org/10.1038/s41585-024-00962-z

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