27 research outputs found
Sentinel node procedure of the sigmoid using indocyanine green: feasibility study in a goat model
Carcinoembryonic antigen-related cell adhesion molecule type 5 receptor-targeted fluorescent intraoperative molecular imaging tracer for lung cancer: a nonrandomized controlled trial
IMPORTANCE Localization of subcentimeter ground glass opacities during minimally invasive thoracoscopic lung cancer resections is a significant challenge in thoracic oncology. Intraoperative molecular imaging has emerged as a potential solution, but the availability of suitable fluorescence agents is a limiting factor.OBJECTIVE To evaluate the suitability of SGM-101, a carcinoembryonic antigen-related cell adhesion molecule type 5 (CEACAM5) receptor-targeted near-infrared fluorochrome, for molecular imagingguided lung cancer resections, because glycoprotein is expressed in more than 80% of adenocarcinomas.DESIGN, SETTING, AND PARTICIPANTS For this nonrandomized, proof-of-principal, phase 1 controlled trial, patients were divided into 2 groups between August 1, 2020, and January 31, 2022. Patients with known CEACAM5-positive gastrointestinal tumors suggestive of lung metastasis were selected as proof-of-principle positive controls. The investigative group included patients with lung nodules suggestive of primary lung malignant neoplasms. Patients 18 years or older without significant comorbidities that precluded surgical exploration with suspicious pulmonary nodules requiring surgical biopsy were included in the study.INTERVENTIONS SGM-101 (10mg) was infused up to 5 days before index operation, and pulmonary nodules were imaged using a near-infrared camera system with a dedicated thoracoscope.MAIN OUTCOMES AND MEASURES SGM-101 localization to pulmonary nodules and its correlation with CEACAM5 glycoprotein expression by the tumor as quantified by tumor and normal pulmonary parenchymal fluorescence.RESULTS Ten patients (5 per group; 5 male and 5 female; median [IQR] age, 66 [58-69] years) with 14 total lesions (median [range] lesion size, 0.91 [0.90-2.00] cm) were enrolled in the study. In the control group of 4 patients (1 patient did not undergo surgical resection because of abnormal preoperative cardiac clearance findings that were not deemed related to SGM-101 infusion), the mean (SD) lesion size was 1.33 (0.48) cm, 2 patients had elevated serum CEA markers, and 2 patients had normal serum CEA levels. Of the 4 patients who underwent surgical intervention, those with 2+ and 3+ tissue CEACAM5 expression had excellent tumor fluorescence, with a mean (SD) tumor to background ratio of 3.11 (0.45). In the patient cohort, the mean (SD) lesion size was 0.68 (0.22) cm, and no elevations in serum CEA levels were found. Lack of SGM-101 fluorescence was associated with benign lesions and with lack of CEACAM5 staining.CONCLUSIONS AND RELEVANCE This in-human proof-of-principle nonrandomized controlled trial demonstrated SGM-101 localization to CEACAM5-positive tumors with the detection of real-time near-infrared fluorescence in situ, ex vivo, and by immunofluorescence microscopy. These findings suggest that SGM-101 is a safe, receptor-specific, and feasible intraoperative molecular imaging fluorochrome that should be further evaluated in randomized clinical trials.Surgical oncolog
Carcinoembryonic antigen-specific, fluorescent image-guided cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer
Protein Kinase C Regulates the Cell Surface Activity of Endothelin-Converting Enzyme-1
Novel human-derived cell penetrating peptides for specific subcellular delivery of therpeutic biomolecules
Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using In-111-Labeled SGM-101
Purpose: Intraoperative image guidance may aid in clinical decision-making during surgical treatment of colorectal cancer. We developed the dual-labeled carcinoembryonic antigen-targeting tracer, [In-111]In-DTPA-SGM-101, for pre- and intra-operative imaging of colorectal cancer. Subsequently, we investigated the tracer in preclinical biodistribution and multimodal image-guided surgery studies, and assessed the clinical feasibility on patient-derived colorectal cancer samples, paving the way for rapid clinical translation.Experimental Design: SGM-101 was conjugated with p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (DTPA) and labeled with Indium-111 (In-111). The biodistribution of 3, 10, 30, and 100 mu g [In-111]In-DTPA-SGM-101 was assessed in a dose escalation study in BALB/c nude mice with subcutaneous LS174T human colonic tumors, followed by a study to determine the optimal timepoint for imaging. Mice with intraperitoneal LS174T tumors underwent micro-SPECT/CT imaging and fluorescence image-guided resection. In a final translational experiment, we incubated freshly resected human tumor specimens with the tracer and assessed the tumor-to-adjacent tissue ratio of both signals.Results: The optimal protein dose of [In-111]In-DTPA-SGM-101 was 30 mu g (tumor-to-blood ratio, 5.8 +/- 1.1) and the optimal timepoint for imaging was 72 hours after injection (tumor-to-blood ratio, 5.1 +/- 1.0). In mice with intraperitoneal tumors, [In-111]In-DTPA-SGM-101 enabled preoperative SPECT/CT imaging and fluorescence image-guided resection. After incubation of human tumor samples, overall fluorescence and radiosignal intensities were higher in tumor areas compared with adjacent nontumor tissue (P < 0.001).Conclusions: [In-111]In-DTPA-SGM-101 showed specific accumulation in colorectal tumors, and enabled micro-SPECT/CT imaging and fluorescence image-guided tumor resection. Thus, [In-111]In-DTPA-SGM-101 could be a valuable tool for preoperative SPECT/CT imaging and intraoperative radio-guided localization and fluorescence image-guided resection of colorectal cancer.Surgical oncolog
Realisation des moyens mis en oeuvre pour l'acquisition en vol de l'ECG d'un pilote et des parametres physiques d'ambiance
SIGLECNRS RP 174 (171) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc