In vivo molecular prediction of carbonic anhydrase IX-G250MN expression on immunotherapy outcome in renal cancer.

TotheEditor: It is with great interest that we read the article of Atkins et al. (1) and the accompanying commentary of Panelli et al. (2) about the possible usefulness of carbonic anhydrase IX-G250MN (CAIX) expression as a biomarker to predict responses to interleukin-2 therapy in renal cell carcinoma. Atkins et al. (1) showed that high-positively CAIX staining [according to Bui et al. (3)] of mostly primary renal cell carcinoma tumors correlated with a significantly better survival rate after interleukin-2 therapy. This is strikingly in line with a previous observation in a study in which we compared the usefulness of the diagnostic imaging modalities [F]FDGpositron emission tomography and immunoscintigraphy with I-labeled chimeric anti-CAIX monoclonal antibody (mAb) G250 (mAb I-cG250) in patients with advanced metastasized renal cell carcinoma (4). We noticed that patients who showed poor accumulation of mAb I-cG250 in most of their metastatic lesions subsequently had rapidly progressive disease. The prognostic value of the molecular marker CAIX expression, as determined on specimens of primary tumors and renal cell carcinoma metastases by Atkins et al. (1) and Bui et al. (3), can be evaluated noninvasively with radioimmunoscintigraphy with the mAb I-cG250 (4). Thus, in vivo molecular imaging with a mAb targeting CAIX (e.g., radiolabeled mAb cG250) holds promise for patient selection [no treatment of nonimmune-responsive tumors as suggested by Panelli et al. (2)] before initiation of therapy in metastatic renal cell carcinoma and for response evaluation during and at the end of therapy. Another advantage of in vivo visualization of CAIX expression with radioimmunoscintigraphy is the possibility to assess the uptake of radiolabeled mAb for each individual lesion as metastases have a lower expression of CAIX than primary tumors (3). Apart from clinical relevance, this noninvasive procedure could add to our understanding of the role of CAIX up-regulation in tumorigenesis of clear cell renal cell carcinoma and its role in the responsiveness of renal cell carcinoma tumors to interleukin-2, other immunotherapies (e.g., IFN-a), or novel experimental treatments that have recently come available for patients with renal cell carcinoma (1, 2). Indeed, more research in this area is warranted.