Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas

• Published in: Molecular therapy 2018-02, Vol.26 (2), p.390-403
• Main Authors: Predina, Jarrod D., Newton, Andrew D., Connolly, Courtney, Dunbar, Ashley, Baldassari, Michael, Deshpande, Charuhas, Cantu, Edward, Stadanlick, Jason, Kularatne, Sumith A., Low, Philip S., Singhal, Sunil
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - diagnostic imaging; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - surgery; Animals; Cancer surgery; Chemotherapy; Contrast agents; Contrast Media; Disease Models, Animal; Feasibility studies; Female; Folate Receptor 1 - genetics; Folate Receptor 1 - metabolism; folate receptor alpha; Folate Receptors, GPI-Anchored - genetics; Folate Receptors, GPI-Anchored - metabolism; Folic acid; Gene Expression; Humans; I.R. radiation; Identification; Immunohistochemistry; Intraoperative Care; intraoperative imaging; Localization; Lung cancer; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - surgery; Male; Medical imaging; Mice; Molecular Imaging - methods; Non-small cell lung carcinoma; Original; Patients; pulmonary adenocarcinoma; Surgeons; surgery; Tumors; Vitamin B; Xenograft Model Antitumor Assays
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2017.10.016

Non-small cell lung cancer (NSCLC) is the number one cancer killer in the United States. Despite attempted curative surgical resection, nearly 40% of patients succumb to recurrent disease. High recurrence rates may be partially explained by data suggesting that 20% of NSCLC patients harbor synchronous disease that is missed during resection. In this report, we describe the use of a novel folate receptor-targeted near-infrared contrast agent (OTL38) to improve the intraoperative localization of NSCLC during pulmonary resection. Using optical phantoms, fluorescent imaging with OTL38 was associated with less autofluorescence and greater depth of detection compared to traditional optical contrast agents. Next, in in vitro and in vivo NSCLC models, OTL38 reliably localized NSCLC models in a folate receptor-dependent manner. Before testing intraoperative molecular imaging with OTL38 in humans, folate receptor-alpha expression was confirmed to be present in 86% of pulmonary adenocarcinomas upon histopathologic review of 100 human pulmonary resection specimens. Lastly, in a human feasibility study, intraoperative molecular imaging with OTL38 accurately identified 100% of pulmonary adenocarcinomas and allowed for identification of additional subcentimeter neoplastic processes in 30% of subjects. This technology may enhance the surgeon’s ability to identify NSCLC during oncologic resection and potentially improve long-term outcomes. [Display omitted] Predina et al. explore folate receptor-targeted intraoperative molecular imaging in preclinical models and humans with non-small cell lung cancer.