Positron Emission Tomography/Computed Tomography Identification of Clear Cell Renal Cell Carcinoma: Results From the REDECT Trial

Abstract

A B S T R A C T PurposeA clinical study to characterize renal masses with positron emission tomography/computed tomography (PET/CT) was undertaken. Patients and MethodsThis was an open-label multicenter study of iodine-124 ( 124 I) -girentuximab PET/CT in patients with renal masses who were scheduled for resection. PET/CT and contrast-enhanced CT (CECT) of the abdomen were performed 2 to 6 days after intravenous 124 I-girentuximab administration and before resection of the renal mass(es). Images were interpreted centrally by three blinded readers for each imaging modality. Tumor histology was determined by a blinded central pathologist. The primary end points-average sensitivity and specificity for clear cell renal cell carcinoma (ccRCC)-were compared between the two modalities. Agreement between and within readers was assessed. Results 124I-girentuximab was well tolerated. In all, 195 patients had complete data sets (histopathologic diagnosis and PET/CT and CECT results) available. The average sensitivity was 86.2% (95% CI, 75.3% to 97.1%) for PET/CT and 75.5% (95% CI, 62.6% to 88.4%) for CECT (P ϭ .023). The average specificity was 85.9% (95% CI, 69.4% to 99.9%) for PET/CT and 46.8% (95% CI, 18.8% to 74.7%) for CECT (P ϭ .005). Inter-reader agreement was high ( range, 0.87 to 0.92 for PET/CT; 0.67 to 0.76 for CECT), as was intrareader agreement (range, 87% to 100% for PET/CT; 73.7% to 91.3% for CECT). ConclusionThis study represents (to the best of our knowledge) the first clinical validation of a molecular imaging biomarker for malignancy. 124I-girentuximab PET/CT can accurately and noninvasively identify ccRCC, with potential utility for designing best management approaches for patients with renal masses.

Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study

“…4 and Table 1). Very recently, immuno-PET imaging and dosimetric studies have been conducted with a different monoclonal antibody (girentuximab), labeled with 124 I or with other radionuclides (9,10,49). Girentuximab is a chimeric monoclonal antibody, specific to carbonic anhydrase IX, one of the best known markers for kidney cancer (50).…”

“…These pharmaceutical developments rely crucially on the antibody's ability to localize at sites of disease. Immuno-PET, a molecular imaging technique combining the high resolution and sensitivity of positron emission tomography (PET) and the selective localization of antibodies at their target in vivo, has profited from recent technical advances and the availability of Good Manufacturing Practice (GMP)-grade radionuclides, and might play an important role in the future both in cancer staging and tailoring of therapy (6)(7)(8)(9)(10).…”

Trimeric Radiofluorinated Sulfonamide Derivatives to Achieve In Vivo Selectivity for Carbonic Anhydrase IX–Targeted PET Imaging

“…Monoclonal antibodies and small-molecule inhibitors have been explored for nuclear imaging. 124 I-cG250, a monoclonal antibody targeting the PG-like domain of CA-IX, advanced to phase III clinical trial for the diagnosis of clear cell renal cell carcinoma (marketed as RENAREX by WILEX AG) (15). Because of concerns with tumor penetrance within hypoxic regions and nonideal delayed imaging, research groups have sought alternatives to monoclonal antibody-based imaging.…”

A 99mTc-Labeled Ligand of Carbonic Anhydrase IX Selectively Targets Renal Cell Carcinoma In Vivo

“…One anti-CAIX antibody in IgG format (cG250), labeled with the PET radionuclide 124 I, is in advanced clinical development for the detection of metastatic lesions in RCC patients (5). However, macromolecular radiotracers, in particular antibodies in IgG format, typically clear slowly from the blood, requiring the use of long-lived radioisotopes and imaging at late time points, which exposes patients to a high radiation burden (6). Indeed, 124 I-cG250 only reaches tumor-to-blood ratios suitable for imaging 2-7 d after injection into the patient.…”