CAIX PET/CT detects 97.9% of clear-cell kidney cancer lesions in prospective study

A prospective multicentre study found that a CAIX-targeted PET/CT approach detected 97.9% of lesions in patients with clear cell renal cell carcinoma, compared with 47.1% using conventional ¹⁸F-FDG PET/CT. The result, presented at the 39th Annual Congress of the European Association of Nuclear Medicine in Vienna, also showed higher patient-level diagnostic accuracy and substantially greater tumour contrast for [⁶⁸Ga]Ga-DPI-4452. Researchers assessed [⁶⁸Ga]Ga-DPI-4452 PET/CT against ¹⁸F-FDG PET/CT in 68 patients recruited at multiple centres.

Across the complete renal cell carcinoma cohort, the CAIX-targeted technique detected 90.9% of the 492 true lesions, while FDG detected 56.7%. The difference was more pronounced in the clear cell renal cell carcinoma subgroup, which accounted for the study’s strongest results: lesion detection reached 97.9% with [⁶⁸Ga]Ga-DPI-4452 and 47.1% with FDG. Patient-level diagnostic accuracy in clear cell disease was 98.2% for the CAIX-targeted technique and 77.2% for ¹⁸F-FDG.

The imaging strategy targets carbonic anhydrase IX, commonly abbreviated CAIX, a protein that the researchers described as being highly expressed in clear cell renal cell carcinoma but minimally expressed in normal renal tissue. Lead author Professor Esra Arslan said: “CAIX gives us a highly selective biological target. 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.” The target therefore offers a way to identify clear cell tumours without relying on the glucose metabolism measured by ¹⁸F-FDG. FDG PET/CT measures glucose metabolism and is commonly used in cancer imaging, but its usefulness in renal cell carcinoma can be limited by high physiological glucose uptake and intense urinary excretion in the kidneys. These processes can make tumours harder to distinguish from surrounding tissue.

Some low-grade tumours also take up relatively little FDG, further complicating their detection. In the prospective comparison, [⁶⁸Ga]Ga-DPI-4452 was designed to target CAIX rather than glucose activity, allowing the investigators to test whether greater selectivity for clear cell renal cell carcinoma would produce more conspicuous lesions and improved detection in this cohort. Quantitative measurements confirmed marked differences in tumour visibility.

Uptake of [⁶⁸Ga]Ga-DPI-4452 in tumours was approximately five times higher than uptake of ¹⁸F-FDG, while the tumour-to-background ratio was around ten times greater overall. The tumour-to-background ratio describes how clearly a tumour stands out from surrounding tissue. In identified brain metastases, for example, the median maximum tumour-to-background ratio was 281.3 for [⁶⁸Ga]Ga-DPI-4452, compared with 0.7 for ¹⁸F-FDG.

These measurements showed that the CAIX-targeted agent generated substantially stronger contrast in the lesions assessed, although they do not by themselves establish better long-term clinical outcomes. Detection differences were also evident at specific metastatic sites. The CAIX-targeted technique detected all identified brain metastases and all identified lung metastases, while FDG detected around half of the lung metastases.

For lymph nodes, detection was 95.0% with [⁶⁸Ga]Ga-DPI-4452 and 68.9% with ¹⁸F-FDG. Brain metastases provided a particularly clear example of the contrast difference because high physiological FDG uptake can make lesions difficult to distinguish. These site-specific findings apply to the lesions identified and evaluated in the study and do not establish equivalent performance for every form or stage of metastatic renal cell carcinoma.

Liver metastases were the main exception in the overall cohort. FDG performed better for liver lesions, which the researchers linked to lower and more variable CAIX expression in some non-clear cell renal cell carcinoma subtypes. Within the clear cell subgroup, however, performance again favoured [⁶⁸Ga]Ga-DPI-4452.

The variation is important for interpreting the headline result: the near-complete detection reported for clear cell renal cell carcinoma should not be treated as a universal performance estimate for renal cell carcinoma. The broader cohort results and the liver finding also show why future studies must account for biological differences among subtypes. The investigators examined whether the imaging results affected decisions about disease stage and treatment.

A change in clinical management or disease stage occurred in 30.9% of patients assessed with [⁶⁸Ga]Ga-DPI-4452, compared with 5.9% after ¹⁸F-FDG. Reported changes included identifying previously undetected recurrent or residual disease and detecting nodal or distant metastases that resulted in upstaging or reclassified some patients from oligometastatic, or limited, disease to more widespread metastatic disease. In three patients, findings considered positive on FDG PET/CT were excluded by the CAIX-targeted examination, which the researchers reported had avoided unnecessary interventions.

The study measured imaging and management changes, not whether those changes ultimately improved survival or other patient outcomes. Arslan and Professor Dr Halil Kömek, who contributed equally to the work, identified possible roles for CAIX-targeted PET/CT in initial staging before nephrectomy or metastasectomy, restaging when recurrence is suspected and, in the future, selection for treatment with a matched radioligand. The proposed theranostic strategy would use [⁶⁸Ga]Ga-DPI-4452 imaging to identify patients who might be suitable for treatment with [¹⁷⁷Lu]Lu-DPI-4452.

That application remains investigational in the congress report. Arslan said [⁶⁸Ga]Ga-DPI-4452 “has the potential to become a valuable tool across several stages of RCC management,” but cautioned that it was premature to call the agent a new molecular imaging standard without validation in larger multicentre studies stratified by subtype. The prospective design and direct comparison strengthen the reported evidence, but several limitations remain.

Longer prospective studies will be needed to determine whether the observed changes in staging and clinical management translate into improved patient outcomes.

Subject of Research: Prospective evaluation of CAIX-targeted PET/CT for detecting renal cell carcinoma lesions in 68 patients.

Article Title: New PET imaging approach detects almost all lesions in common form of kidney cancer

Article References: New PET imaging approach detects almost all lesions in common form of kidney cancer. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

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Keywords: CAIX-targeted PET/CT, clear cell renal cell carcinoma, kidney cancer, positron emission tomography, ¹⁸F-FDG PET/CT, carbonic anhydrase IX, lesion detection, cancer staging, metastases, EANM 2026, imaging, approach