# Nuclear Imaging in Renal Cell Carcinoma: Current Evidence and Clinical Applications

## TL;DR

This review explores how nuclear imaging techniques can provide biological insights into kidney cancer beyond standard imaging, potentially improving diagnosis and treatment decisions.

## Contribution

The paper summarizes current evidence on various nuclear imaging techniques for renal cell carcinoma and their clinical applications.

## Key findings

- [18F]FDG PET/CT is effective for staging and prognosis in advanced kidney cancer.
- PSMA PET/CT improves detection of metastatic clear-cell renal cancer and can influence treatment decisions.
- Sestamibi imaging helps distinguish benign from malignant renal tumors, reducing unnecessary surgeries.

## Abstract

Standard imaging for kidney cancer mainly shows the size and location of tumours but provides limited information about tumour biology. Radiotracer-based nuclear imaging uses specialised tracers to visualise cancer metabolism, blood supply, and the tumour microenvironment, offering additional biological insight. This review summarises current evidence of the nuclear imaging used in renal cell carcinoma, including [18F]FDG PET/CT, PSMA PET/CT, [99mTc]-sestamibi SPECT/CT, CAIX PET/CT, and FAPI PET/CT. [18F]FDG PET is useful for staging and prognosis in advanced disease. PSMA PET may improve the detection of metastatic clear-cell renal cancer and can influence treatment decisions. Sestamibi imaging may help distinguish benign oncocytic tumours from malignant renal cancers, potentially avoiding unnecessary surgery. CAIX and FAPI tracers represent emerging tools that may support more precise diagnosis and targeted therapies. Together, these nuclear imaging techniques may enhance personalised care for patients with kidney cancer.

Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and magnetic resonance imaging (MRI) remain the diagnostic standard, accumulating evidence suggests that selected nuclear imaging techniques may offer incremental value in specific clinical scenarios. Methods: A narrative literature review was performed using PubMed, Embase, and Web of Science to identify preclinical, retrospective, and prospective studies evaluating PET and SPECT radiotracers in localised and metastatic RCC. Priority was given to meta-analyses, multicentre prospective trials, and studies with histopathological correlation. Results: [18F]fluorodeoxyglucose (FDG) PET/CT demonstrates limited sensitivity for primary renal tumours (pooled sensitivity of approximately 60%) but performs substantially better in metastatic and recurrent disease (pooled sensitivity and specificity of approximately 85–90%), where uptake correlates with tumour grade, progression-free survival, and overall survival. [99mTc]sestamibi SPECT/CT differentiates oncocytoma and hybrid oncocytic/chromophobe tumours from malignant RCC with pooled sensitivity and specificity of around 85–90%, supporting its role in evaluating indeterminate renal masses rather than staging. Prostate-specific membrane antigen (PSMA) PET/CT shows high detection rates in clear-cell RCC, particularly in metastatic disease, with reported sensitivities of approximately 85–90% and management changes in up to 40–50% of selected cohorts. Carbonic anhydrase IX (CAIX)-targeted PET/CT enables the biologically specific visualisation of clear-cell RCC, achieving sensitivities and specificities in the range of 85–90% in prospective phase II and III trials for primary tumour characterisation. Fibroblast activation protein inhibitor (FAPI) PET/CT demonstrates high tumour-to-background uptake in early RCC studies, but evidence remains preliminary, with small cohorts and recognised non-specific uptake in benign inflammatory and fibrotic conditions. Conclusions: Radiotracer-based nuclear imaging provides complementary, biology-driven insights in RCC that extend beyond anatomical assessment. While most modalities remain adjunctive or investigational and are not recommended for routine use, selective application in carefully chosen clinical scenarios may enhance tumour characterisation, prognostication, and personalised treatment planning.