Utilization of targeted near-infrared molecular imaging to improve pulmonary metastasectomy of osteosarcomas

Abstract

Pulmonary metastasectomy for osteosarcoma provides a select group of patients an opportunity for long-term survival and possible cure. Unfortunately, a complete metastasectomy is challenging due an inability to accurately identify lesions that lay below the threshold of preoperative imaging or intraoperative visual and tactile inspection. Growing evidence suggests that osteosarcomas express a number of unique molecular markers, including the folate receptor alpha. In this case report, we describe the application of a folate receptor-targeted, near-infrared optical contrast agent (OTL38) to improve osteosarcoma localization during minimally invasive pulmonary resection. In addition to localizing preoperatively identified lesions, this technology helped identify additional disease that was undetected on preoperative imaging or with traditional intraoperative techniques. This report marks the first successful utilization of a molecular imaging probe useful for osteosarcomas. This technology may provide a unique approach to improve pulmonary metastasectomy of osteosarcomas.

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

“…FR-IMI localized GGOs representing inflammatory processes, adenocarcinoma in situ , minimally invasive adenocarcinoma, and invasive pulmonary adenocarcinoma. This fits nicely with our previous work demonstrating successful localization of solid pulmonary masses including pulmonary adenocarcinomas, pulmonary squamous cell carcinomas [13] and pulmonary metastases [14]. Intraoperatively, FR-IMI impacted care of 9 of 20 subjects by improving minimally invasive localization (n=6) and identifying close margins (n=3).…”

Intraoperative fluorescence imaging in thoracic surgery

“…OTL38 is also a promising agent for targeted IFI of osteosarcoma pulmonary metastases. Osteosarcomas frequently have upregulated FRα, and we discovered that targeted IFI with OTL38 can identify osteosarcoma pulmonary metastases …”

Current Strategies and Applications for Precision Drug Design

“…OTL38 is currently being developed in several clinical trials, including a phase 3 ovarian cancer study (with safety already be tested in a phase 2 study), and a phase 2 exploratory study of identifying pulmonary nodules ( van Dam et al, 2011 ; Hoogstins et al, 2016 ). Moreover, treatments of additional cancer types including pituitary neoplasms, renal cell carcinoma, bladder cancer and gastric cancer are also undergoing clinical trial for testing OLT38’s safety and efficacy ( Predina et al, 2017a , 2018 ).…”