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      Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study

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          Intraoperative imaging with antibodies labeled with both a radionuclide for initial guidance and a near-infrared dye for adequate tumor delineation may overcome the main limitation of fluorescence imaging: the limited penetration depth of light in biological tissue. In this study, we demonstrate the feasibility and safety of intraoperative dual-modality imaging with the carbonic anhydrase IX (CAIX)-targeting antibody 111In-DOTA-girentuximab-IRDye800CW in clear cell renal cell carcinoma (ccRCC) patients.

          Methods: A phase I protein dose escalation study was performed in patients with a primary renal mass who were scheduled for surgery. 111In-DOTA-girentuximab-IRDye800CW (5, 10, 30, or 50 mg, n=3 ccRCC patients per dose level) was administered intravenously and after 4 days SPECT/CT imaging was performed. Seven days after antibody injection, surgery was performed with the use of a gamma probe and near-infrared fluorescence camera.

          Results: In total, fifteen patients were included (12 ccRCC, 3 CAIX-negative tumors). No study-related serious adverse events were observed. All ccRCC were visualized by SPECT/CT and localized by intraoperative gamma probe detection (mean tumor-to-normal kidney (T:N) ratio 2.5 ± 0.8), while the T:N ratio was 1.0 ± 0.1 in CAIX-negative tumors. ccRCC were hyperfluorescent at all protein doses and fluorescence imaging could be used for intraoperative tumor delineation, assessment of the surgical cavity and detection of (positive) surgical margins. The radiosignal was crucial for tumor localization in case of overlying fat tissue.

          Conclusion: This first in man study shows that tumor-targeted dual-modality imaging using 111In-DOTA-girentuximab-IRDye800CW is safe and can be used for intraoperative guidance of ccRCC resection.

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          Preoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (124I-cG250) and PET in patients with renal masses: a phase I trial.

          Preoperative identification of tumour type could have important implications for the choice of treatment for renal cancers. Antibody cG250 reacts against carbonic anhydrase-IX, which is over-expressed in clear-cell renal carcinomas. We aimed to assess whether iodine-124-labelled antibody chimeric G250 ((124)I-cG250) PET predicts clear-cell renal carcinoma, the most common and aggressive renal tumour. 26 patients with renal masses who were scheduled to undergo surgical resection by laparotomy received a single intravenous infusion of 185 MBq/10 mg of (124)I-cG250 over 20 min in this open-label pilot study. Surgery was scheduled 1 week after (124)I-cG250 infusion. PET and CT scanning of the abdomen, including the kidneys, within 3 h before surgery was planned for all patients. The obtained images were graded as positive (defined as a tumour-to-healthy-kidney ratio >3 to 1) or negative for antibody uptake, and the surgeon was informed of the scan results before surgery. After surgery, resected tumours were histopathologically classified as clear-cell renal carcinoma or otherwise. The trial is registered on the clinical trials site of the National Cancer Institute website One patient received inactive antibody and was excluded from analysis. 15 of 16 clear-cell carcinomas were identified accurately by antibody PET, and all nine non-clear-cell renal masses were negative for the tracer. The sensitivity of (124)I-cG250 PET for clear-cell kidney carcinoma in this trial was 94% (95% CI 70-100%); the negative predictive value was 90% (55-100%), and specificity and positive predictive accuracy were both 100% (66-100% and 78-100%, respectively). PET with (124)I-cG250 can identify accurately clear-cell renal carcinoma; a negative scan is highly predictive of a less aggressive phenotype. Stratification of patients with renal masses by (124)I-cG250 PET can identify aggressive tumours and help decide treatment.
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            Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1b and T2 Renal Tumors: A Systematic Review and Meta-analysis of Comparative Studies

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              Positron emission tomography/computed tomography identification of clear cell renal cell carcinoma: results from the REDECT trial.

              A clinical study to characterize renal masses with positron emission tomography/computed tomography (PET/CT) was undertaken. This 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. (124)I-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 = .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 = .005). Inter-reader agreement was high (κ 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). This study represents (to the best of our knowledge) the first clinical validation of a molecular imaging biomarker for malignancy. (124)I-girentuximab PET/CT can accurately and noninvasively identify ccRCC, with potential utility for designing best management approaches for patients with renal masses.

                Author and article information

                Ivyspring International Publisher (Sydney )
                8 March 2018
                : 8
                : 8
                : 2161-2170
                [1 ]Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, The Netherlands.
                [2 ]Department of Urology, Radboudumc, Nijmegen, The Netherlands.
                [3 ]Department of Pathology, Radboudumc, Nijmegen, The Netherlands.
                [4 ]The Institute of Cancer Research and The Royal Marsden Hospital, London, United Kingdom.
                Author notes
                ✉ Corresponding author: Marlène C.H. Hekman, Dept. of Radiology & Nuclear Medicine, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, marlene.hekman@ , Tel: 024-3614048, Fax: 024- 3618942.

                Competing Interests: The authors have declared that no competing interest exists.

                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.

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