A new PET imaging approach detected 97.9% of lesions in clear cell renal cell carcinoma (ccRCC), potentially giving clinicians a more complete picture of the location and extent of a patient's disease, according to research presented today at the 39th Annual Congress of the European Association of Nuclear Medicine (EANM'26) .¹
Renal cell carcinoma (RCC) is the most common form of kidney cancer, with ccRCC its most common subtype.² While ¹⁸F-FDG is commonly used as a radiotracer in cancer PET/CT imaging, it has limitations in RCC, driving interest in more targeted imaging approaches.3-7
Against this background, researchers investigated a different imaging approach targeting carbonic anhydrase IX (CAIX), a protein highly expressed in ccRCC but with minimal expression in normal renal tissue. In a prospective multicentre study of 68 patients with RCC, researchers compared the CAIX-targeted imaging agent [⁶⁸Ga]Ga-DPI-4452 PET/CT with ¹⁸F-FDG PET/CT.3
Across 492 true lesions evaluated in the study, [⁶⁸Ga]Ga-DPI-4452 PET/CT detected 90.9%, compared with 56.7% using ¹⁸F-FDG PET/CT. The difference was even greater in ccRCC, where [⁶⁸Ga]Ga-DPI-4452 PET/CT detected 97.9% of lesions compared with 47.1% using ¹⁸F-FDG PET/CT. Patient-level diagnostic accuracy in ccRCC was also higher, at 98.2% compared with 77.2%.
"CAIX gives us a highly selective biological target," explained lead author Professor Esra Arslan. "It is expressed at a very high rate in ccRCC, while expression in normal renal tissue remains minimal. This gives us the potential to distinguish tumour from surrounding healthy tissue much more clearly."
By contrast, ¹⁸F-FDG measures glucose metabolism, but its effectiveness in RCC can be limited by high physiological glucose uptake and intense urinary excretion in the kidneys, which can make tumours harder to distinguish from surrounding tissue. Some low-grade tumours also take up relatively little ¹⁸F-FDG, making them more difficult to detect.
Tumour uptake with [⁶⁸Ga]Ga-DPI-4452 was approximately five times higher than with ¹⁸F-FDG, while the tumour-to-background ratio — a measure of how clearly a tumour stands out from surrounding tissue — was around ten times greater. Higher lesion detection was seen across several metastatic sites, including the lymph nodes, lungs, bones, brain and soft tissues.
The difference was particularly striking in brain metastases, where high physiological ¹⁸F-FDG uptake can make lesions difficult to distinguish. [⁶⁸Ga]Ga-DPI-4452 PET/CT detected all identified brain metastases, with a median maximum tumour-to-background ratio of 281.3 compared with 0.7 for ¹⁸F-FDG. [⁶⁸Ga]Ga-DPI-4452 PET/CT also detected all identified lung metastases compared with around half using ¹⁸F-FDG PET/CT, while lymph-node detection was 95.0% versus 68.9%.
One exception was liver metastases. Across the overall RCC cohort, FDG performed better in the liver, reflecting lower and more variable CAIX expression in some non-clear cell RCC subtypes. Within the ccRCC subgroup, however, performance again favoured [⁶⁸Ga]Ga-DPI-4452.
Importantly, [⁶⁸Ga]Ga-DPI-4452 PET/CT resulted in a change in clinical management or disease stage in 30.9% of patients, compared with 5.9% using ¹⁸F-FDG PET/CT. Changes included identifying previously undetected recurrent or residual disease, detecting nodal or distant metastases that resulted in upstaging and reclassifying some patients from oligometastatic to more widespread metastatic disease. In three patients, findings considered positive on ¹⁸F-FDG PET/CT were excluded by [⁶⁸Ga]Ga-DPI-4452 PET/CT, which the researchers reported avoided unnecessary interventions.
Looking ahead, the researchers, Professor Arslan and Professor Dr Halil Kömek, who contributed equally to this work, see potential roles for CAIX-targeted PET/CT in initial staging before nephrectomy or metastasectomy, restaging when recurrence is suspected and, in the future, as part of a theranostic approach in which [⁶⁸Ga]Ga-DPI-4452 PET/CT could help identify patients suitable for treatment with [¹⁷⁷Lu]Lu-DPI-4452.
"[⁶⁸Ga]Ga-DPI-4452 has the potential to become a valuable tool across several stages of RCC management," said Professor Arslan. "However, it is premature to claim that this agent represents a 'new molecular imaging standard' without validation in larger, multicentre studies stratified by subtype."
Further research will be needed to validate the findings in larger patient populations and across different RCC subtypes, where CAIX expression can be lower and more variable. Longer-term prospective studies will also be important to determine whether the observed changes in disease staging and clinical management ultimately translate into improved patient outcomes.
