Within nephro-urology, improved molecular imaging is essential for enhancing diagnostic precision, staging, and treatment planning, particularly in settings where conventional imaging lacks sensitivity or specificity. Positron Emission Tomography (PET) is a key tool in molecular imaging, providing the opportunity to non-invasively visualise both metabolic and receptor-based processes in a range of benign and malignant diseases.

In urological oncology, PET has become well established through the clinical approval of prostate-specific membrane antigen (PSMA)-targeted imaging tracers.1 PSMA imaging has begun to transform clinical management of prostate cancer by enabling a more accurate detection of both primary and metastatic lesions improving diagnosis and evaluation of disease burden whilst outperforming conventional imaging such as computed tomography (CT), MRI, and bone scintigraphy.1, 2, 3, 4 Beyond prostate cancer, 18F-fluorodeoxyglucose (18F-FDG) PET has been applied in nephro-urological assessment. 18F-FDG has been studied in renal cell carcinoma (RCC), upper and lower urothelial carcinomas, as well as in inflammatory and infectious conditions involving the kidneys and urinary tract.5 However, it is not typically used as a first-line diagnostic technique because of variable tracer uptake and high urinary excretion that often obscures lesions, and it is therefore not recommended for routine use in European Society for Medical Oncology (ESMO) guideline for renal cell carcinoma.6,7 Outside 18F-FDG, there are a limited number of PET radiotracers for nephro-urological conditions that have been clinically tested or are in clinical development, as summarised in Fig. 1. For example, those include experimental uses of 18F/68Ga-PSMA for bladder cancer and 2-deoxy-2-18F-fluoro-D-sorbitol (18F-FDS) for functional assessment.8, 9, 10 In parallel with the development of new radiotracers, several emerging agents are currently being tested in clinical investigations, including 89Zr‑girentuximab and 68Ga-DPI-4452 for clear-cell RCC and 68Ga-EDTA for functional measurements for glomerular filtration.11,12 Among these, 68Ga-DPI-4452—a carbonic anhydrase IX–targeted peptide—has recently shown promising first‑in‑human safety, dosimetry and tumour-visualisation characteristics in patients with clear-cell RCC (ccRCC).13 However, despite these advances, many unmet needs remain, especially for imaging fibrosis, stromal changes, and inflammation that are important in many nephro-urological diseases.

Within this context, fibroblast activation protein (FAP)-targeted radiotracers have emerged as a promising new generation of PET agents. They take advantage of the increased numbers of activated fibroblasts and myofibroblasts that appear in many disease settings, driven by healing processes in response to pathological conditions.14 When this reparative process becomes chronic or dysregulated, activated fibroblasts accumulate and drive maladaptive fibrosis and stromal remodelling, and therefore may serve as a potential biomarker of dysfunction in a variety of conditions.14 Given that the expression of FAP is increased on these activated fibroblasts, while largely absent in healthy organs including renal and urologic tissues, FAP-targeted radiotracers offer a unique opportunity to noninvasively visualise fibroinflammatory activity. This makes them particularly promising in nephro-urology, where early detection and quantification of renal fibrosis, obstructive uropathies, post-surgical tissue remodelling, and tumour-associated stroma could substantially improve diagnostic precision, treatment planning, and longitudinal monitoring.

This review aims to provide an overview of FAP-targeted PET imaging in nephro-urology, highlighting its mechanistic basis, discussing early preclinical and clinical data, and how it may complement or surpass existing radiotracers to improve diagnostic accuracy, risk stratification, and patient management.