Introduction
- The clear cell renal cell carcinoma (ccRCC) represents only about half of the tumors enhancing on CECT.
- At the same time, about 90% of patients who present with or later develop metastatic renal cell carcinoma have the clear cell histological subtype.
- Therefore, identifying the ccRCC among the other massess enhancing on CT is very important.
- Biopsy of renal masses is not done routinely because it is technically challenging and might cause seeding of tumor cells along the path of the biopsy needle.
CAIX
- Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is constitutively over expressed in the vast majority of ccRCC and is also variably expressed in other malignancies such as ovarian, colorectal, lung, etc based on their degree of hypoxia.
- But it is absent in most normal tissues with the exception of epithelial cells of the stomach, small bowel or bile ducts.
- Although the expression of CAIX varies in most cancers, it is almost universally expressed in ccRCC.
- CAIX protein is a transmembrane enzyme involved in cellular pH regulation and appears to play a role in regulation of cell proliferation in response to hypoxic conditions and may also be involved in oncogenesis and tumor progression.
- CAIX as a potential tumor marker was first described by Oosterwijik et al.
CAIX Imaging
- Given the potential for CIAX to serve as non invasive imaging biomarker for the presence of ccRCC in an otherwise indeterminate renal mass, a number of small molecules and monoclonal antibody based agents have been investiagted in either preclinical or clinical trial setting.
- Pivotal trials have taken place with radiolabelled version of the g250 monoclonal antibody (Girentuximan) to CAIX.
- First such trial is REDECT. REDECT trial showed the agent was not as useful for lesions less than 2 cm in diameter or in nonclear cell RCC. The advantage of this agents are that it is specific for ccRCC and has a sensitivity comparable with biopsy, but the disadvantage is that less common, but nevertheless aggressive cancers maybe negative.
- It may play a role in patients too ill to undergo biopsy or in those patients for whom adequate conventional studies cannot be obtained.
- However, the study requires 3 to 7 days because of the long clearance time of the antibody and this may make it impractical.
- More recently a confirmatory phase III trial for the girentuximab antibody has been undertaken, but utilizing the zirconium 89 radionuclides - ZIRCON trial. For massess <4cm, sensitivity was 85% and specificity was 90%. These findings suggest that CAIX imaging can be a non invasive means by which to characterise renal mass.
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References
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