Jarrod D Predina1,2, Olugbenga Okusanya1,2, Andrew D Newton1,2, Philip Low3, Sunil Singhal4,5. 1. Department of Surgery, Perelman School of Medicine, University of Pennsylvania School of Medicine, 6 White Building, 3400 Spruce Street, Philadelphia, PA, 19104, USA. 2. Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA. 3. Department of Chemistry, Purdue University, West Lafayette, IN, USA. 4. Department of Surgery, Perelman School of Medicine, University of Pennsylvania School of Medicine, 6 White Building, 3400 Spruce Street, Philadelphia, PA, 19104, USA. sunil.singhal@uphs.upenn.edu. 5. Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA. sunil.singhal@uphs.upenn.edu.
Abstract
PURPOSE: Intraoperative molecular imaging (IMI) is an emerging technology used to locate pulmonary adenocarcinomas and identify positive margins during surgery. Background noise and tissue autofluorescence have been major obstacles. The goal of this study is to optimize the image quality of folate receptor alpha (FRα) targeted IMI for pulmonary adenocarcinomas by modifying emission data. PROCEDURES: A total of 15 lung cancer patients were enrolled in a pilot study. In the first cohort, FRα upregulation within pulmonary adenocarcinoma tumors was confirmed by analyzing specimens from five pulmonary adenocarcinoma patients with flow cytometry and immunohistochemistry. Next, in a cohort of five additional patients, autofluorescence of intrathoracic structures and tissues was quantified. Lastly, five patients with tumors at various depths from the pleural surface were enrolled and received the FRα-targeted optical contrast agent, EC17. In this final cohort, resected pulmonary adenocarcinomas were imaged at a wide range of fluorescence exposure times (0 to 200 ms), various laser powers, and with unique filter configurations. Tumor-to-noise ratio (TNR) for images was generated using region of interest software. RESULTS: Pulmonary adenocarcinomas highly express FRα. Significant autofluorescence from native thoracic tissues was found with the highest fluorescent signals at the bronchial stump (547 ± 98, range 423-699), the pulmonary artery (267 ± 64, range 200-374), and cortical bone (266 ± 17, range 243-287). High levels of autofluorescence were appreciated after systemic administration of EC17; however, TNR was improved by altering exposure settings at the time of the imaging. Optimal fluorescent exposure time occurs at 40 ms (25 frames/s). CONCLUSIONS: Exposure properties can be manipulated to maximize TNR thus allowing for successful intraoperative detection of pulmonary adenocarcinomas during surgery. Optimization of the conditions for intraoperative molecular imaging sets the stage for future clinical trials utilizing targeted IMI techniques which can aid the surgeon at the time of cancer resection.
PURPOSE: Intraoperative molecular imaging (IMI) is an emerging technology used to locate pulmonary adenocarcinomas and identify positive margins during surgery. Background noise and tissue autofluorescence have been major obstacles. The goal of this study is to optimize the image quality of folate receptor alpha (FRα) targeted IMI for pulmonary adenocarcinomas by modifying emission data. PROCEDURES: A total of 15 lung cancerpatients were enrolled in a pilot study. In the first cohort, FRα upregulation within pulmonary adenocarcinoma tumors was confirmed by analyzing specimens from five pulmonary adenocarcinomapatients with flow cytometry and immunohistochemistry. Next, in a cohort of five additional patients, autofluorescence of intrathoracic structures and tissues was quantified. Lastly, five patients with tumors at various depths from the pleural surface were enrolled and received the FRα-targeted optical contrast agent, EC17. In this final cohort, resected pulmonary adenocarcinomas were imaged at a wide range of fluorescence exposure times (0 to 200 ms), various laser powers, and with unique filter configurations. Tumor-to-noise ratio (TNR) for images was generated using region of interest software. RESULTS:Pulmonary adenocarcinomas highly express FRα. Significant autofluorescence from native thoracic tissues was found with the highest fluorescent signals at the bronchial stump (547 ± 98, range 423-699), the pulmonary artery (267 ± 64, range 200-374), and cortical bone (266 ± 17, range 243-287). High levels of autofluorescence were appreciated after systemic administration of EC17; however, TNR was improved by altering exposure settings at the time of the imaging. Optimal fluorescent exposure time occurs at 40 ms (25 frames/s). CONCLUSIONS: Exposure properties can be manipulated to maximize TNR thus allowing for successful intraoperative detection of pulmonary adenocarcinomas during surgery. Optimization of the conditions for intraoperative molecular imaging sets the stage for future clinical trials utilizing targeted IMI techniques which can aid the surgeon at the time of cancer resection.
Entities:
Keywords:
FRα; Intraoperative molecular imaging (IMI); Pulmonary adenocarcinoma; Tumor-to-noise ratio
Authors: Joost R van der Vorst; Boudewijn E Schaafsma; Merlijn Hutteman; Floris P R Verbeek; Gerrit-Jan Liefers; Henk H Hartgrink; Vincent T H B M Smit; Clemens W G M Löwik; Cornelis J H van de Velde; John V Frangioni; Alexander L Vahrmeijer Journal: Cancer Date: 2013-06-21 Impact factor: 6.860
Authors: Nikki Parker; Mary Jo Turk; Elaine Westrick; Jeffrey D Lewis; Philip S Low; Christopher P Leamon Journal: Anal Biochem Date: 2005-03-15 Impact factor: 3.365
Authors: L T Mantovani; S Miotti; S Ménard; S Canevari; F Raspagliesi; C Bottini; F Bottero; M I Colnaghi Journal: Eur J Cancer Date: 1994 Impact factor: 9.162
Authors: Jack X Jiang; Jane J Keating; Elizabeth M De Jesus; Ryan P Judy; Brian Madajewski; Ollin Venegas; Olugbenga T Okusanya; Sunil Singhal Journal: Am J Nucl Med Mol Imaging Date: 2015-06-15
Authors: Daniel J O'Shannessy; Gordon Yu; Robert Smale; Yao-Shi Fu; Sunil Singhal; Robert P Thiel; Elizabeth B Somers; Anil Vachani Journal: Oncotarget Date: 2012-04
Authors: Quirijn R J G Tummers; Charlotte E S Hoogstins; Katja N Gaarenstroom; Cor D de Kroon; Mariette I E van Poelgeest; Jaap Vuyk; Tjalling Bosse; Vincent T H B M Smit; Cornelis J H van de Velde; Adam F Cohen; Philip S Low; Jacobus Burggraaf; Alexander L Vahrmeijer Journal: Oncotarget Date: 2016-05-31
Authors: Elizabeth De Jesus; Jane J Keating; Sumith A Kularatne; Jack Jiang; Ryan Judy; Jarrod Predina; Shuming Nie; Philip Low; Sunil Singhal Journal: Int J Mol Imaging Date: 2015-09-28
Authors: Jarrod D Predina; Andrew D Newton; Courtney Connolly; Ashley Dunbar; Michael Baldassari; Charuhas Deshpande; Edward Cantu; Jason Stadanlick; Sumith A Kularatne; Philip S Low; Sunil Singhal Journal: Mol Ther Date: 2017-10-26 Impact factor: 11.454
Authors: John Y K Lee; Steve S Cho; Walter Stummer; Janos L Tanyi; Alexander L Vahrmeijer; Eben Rosenthal; Barbara Smith; Eric Henderson; David W Roberts; Amy Lee; Constantinos G Hadjipanayis; Jeffrey N Bruce; Jason G Newman; Sunil Singhal Journal: J Biomed Opt Date: 2019-12 Impact factor: 3.170