Dataset Information

Localization of Pulmonary Ground-Glass Opacities with Folate Receptor-Targeted Intraoperative Molecular Imaging.

ABSTRACT: PURPOSE:Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor-targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins. METHODS:In a human trial, 20 subjects with pulmonary GGOs who were eligible for video-assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near-infrared imaging. RESULTS:We observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near-infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited. CONCLUSIONS:This approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial.

SUBMITTER: Predina JD

PROVIDER: S-EPMC6015787 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Localization of Pulmonary Ground-Glass Opacities with Folate Receptor-Targeted Intraoperative Molecular Imaging.

Predina Jarrod D JD Newton Andrew A Corbett Christopher C Xia Leilei L Sulyok Lydia Frenzel LF Shin Michael M Deshpande Charuhas C Litzky Leslie L Barbosa Eduardo E Low Philip S PS Kucharczuk John C JC Singhal Sunil S

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20180404 7

<h4>Purpose</h4>Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging ...[more]

PMID: 29626619

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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:Objective: Pure ground-glass opacity (GGO) nodules have been detected with increasing frequency using computed tomography (CT). We performed a retrospective study to clarify whether lung cancer patient prognoses correlated with pure GGO nodules. We also analyzed the clinical characters of patients with pure GGO nodules to provide diagnostic guidance on lung cancer identification and treatment of patients in clinical practice. Methods: We enrolled 39 of 1422 patients with pure GGO nodules who accepted surgical treatment of the lung cancer nodules, and reviewed materials from 404 patients to verify our conclusions. To discover which factors were prognostically significant, we used the Kaplan-Meier method to estimate the overall survival (OS) and progression-free survival (PFS) curves. Age, gender, smoking history, histology, tumor size, and stage were the factors examined in our study. We also performed subgroup and matching group analyses to clarify the correlation between the presence of pure GGO nodules and prognoses. Results: Pure GGO nodules were associated with non-smoking females that had adenocarcinoma. The prognoses of patients in the pure GGO nodule group was better than those in the non-pure GGO nodule group (p = 0.046). Age, grade, and stage (including tumor size and lymph node metastases) were had prognostic significance. In the matching group stage assessments, although patient prognoses were not significantly different among patients of the GGO group compared with thoses of the other group in long-term, while in the short term, patients with pure GGO nodules had longer PFS. Non-smoking female patients with lung cancer were more likely to have adenocarcinoma. Conclusions: As a subgroup of GGO nodules, pure GGO nodules predict a better prognosis in all lung cancer patients. Wheras our study showed that lung patients with pure GGO nodules in similar stages were not significantly different in long-term prognoses, in the short term; patients with pure GGO nodules had longer PFS.

Dataset Information

Localization of Pulmonary Ground-Glass Opacities with Folate Receptor-Targeted Intraoperative Molecular Imaging.

Publications

Localization of Pulmonary Ground-Glass Opacities with Folate Receptor-Targeted Intraoperative Molecular Imaging.

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