Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Hekman MC

PROVIDER: S-EPMC5928878 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Hekman Marlène C MC Rijpkema Mark M Muselaers Constantijn H CH Oosterwijk Egbert E Hulsbergen-Van de Kaa Christina A CA Boerman Otto C OC Oyen Wim J WJ Langenhuijsen Johan F JF Mulders Peter F PF

Theranostics 20180308 8

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 <sup>111</sup>In-DOTA-girentuximab-IRDye800CW in clear cell renal cell carcinom ...[more]

PMID: 29721070

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Project description:Complete resection of tumor lesions in advanced stage ovarian cancer patients is of utmost importance, since the extent of residual disease after surgery strongly affects survival. Intraoperative imaging may be useful to improve surgery in these patients. Farletuzumab is a humanized IgG1 antibody that specifically recognizes the folate receptor alpha (FRα). Labeled with a radiolabel and a fluorescent dye, farletuzumab may be used for the intraoperative detection of ovarian cancer lesions. The current aim is to demonstrate the feasibility of FRα-targeted dual-modality imaging using 111In-farletuzumab-IRDye800CW in an intraperitoneal ovarian cancer model. Biodistribution studies were performed 3 days after injection of 3, 10, 30, or 100 μg of 111In-farletuzumab-IRDye800CW in mice with subcutaneous IGROV-1 tumors (5 mice per group). In mice with intraperitoneal IGROV-1 tumors the nonspecific uptake of 111In-farletuzumab-IRDye800CW was determined by coinjecting an excess of unlabeled farletuzumab. MicroSPECT/CT and fluorescence imaging were performed 3 days after injection of 10 μg of 111In-farletuzumab-IRDye800CW. FRα expression in tumors was determined immunohistochemically. Optimal tumor-to-blood-ratios (3.4-3.7) were obtained at protein doses up to 30 μg. Multiple intra-abdominal tumor lesions were clearly visualized by microSPECT/CT, while uptake in normal tissues was limited. Fluorescence imaging was used to visualize and guide resection of superficial tumors. Coinjection of an excess of unlabeled farletuzumab significantly decreased tumor uptake of 111In-farletuzumab-IRDye800CW (69.4 ± 27.6 versus 18.3 ± 2.2% ID/g, p < 0.05). Immunohistochemical analyses demonstrated that the radioactive and fluorescent signal corresponded with FRα-expressing tumor lesions. FRα-targeted SPECT/fluorescence imaging using 111In-farletuzumab-IRDye800CW can be used to detect ovarian cancer in vivo and could be a valuable tool for enhanced intraoperative tumor visualization in patients with intraperitoneal metastases of ovarian cancer.

Project description:BackgroundThe high drug resistance and metabolic reprogramming of clear cell renal cell carcinoma (ccRCC) are considered responsible for poor prognosis. In-depth research at multiple levels is urgently warranted to illustrate the lipid composition, distribution, and metabolic pathways of clinical ccRCC specimens.MethodsIn this project, a leading-edge targeted quantitative lipidomic study was conducted using 10 pairs of cancerous and adjacent normal tissues obtained from ccRCC patients. Accurate lipid quantification was performed according to a linear equation calculated using internal standards. Qualitative and quantitative analyses of lipids were performed with multiple reaction monitoring analysis based on ultra-performance liquid chromatography (UPLC) and mass spectrometry (MS). Additionally, a multivariate statistical analysis was performed using data obtained on lipids.ResultsA total of 28 lipid classes were identified. Among them, the most abundant were triacylglycerol (TG), diacylglycerol (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Cholesteryl ester (CE) was the lipid exhibiting the most considerable difference between normal samples and tumor samples. Lipid content, chain length, and chain unsaturation of acylcarnitine (CAR), CE, and DG were found to be significantly increased. Based on screening for variable importance in projection scores ≥1, as well as fold change limits between 0.5 and 2, 160 differentially expressed lipids were identified. CE was found to be the most significantly upregulated lipid, while TG was observed to be the most significantly downregulated lipid.ConclusionBased on the absolute quantitative analysis of lipids in ccRCC specimens, it was observed that the content and change trends varied in different lipid classes. Upregulation of CAR, CE, and DG was observed, and analysis of changes in the distribution helped clarify the causes of lipid accumulation in ccRCC and possible carcinogenic molecular mechanisms. The results and methods described herein provide a comprehensive analysis of ccRCC lipid metabolism and lay a theoretical foundation for cancer treatment.

Dataset Information

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

Publications

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

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