Abstract 3586: In vivo targeted detection and imaging of ovarian cancer by SPMR and MRI using anti-folate receptor functionalized iron oxide nanoparticles
Authors: Zhang Marie , Kandasamy Kathirvel , Perera Yamitha , Inglese Dan , Smith-Nguyen Eric 
Published: June 2023

Abstract
Ovarian cancer is the second most common and most deadly gynecological cancer in women. Early and accurate detection is crucial in improving survival rate and quality of life of patients. Folate receptor alpha (FRα) is a folate transporter that has been reported to be overexpressed in approximately 90% of ovarian cancer, which makes it a suitable molecular target to use in developing tumor imaging methods. Iron oxide nanoparticles (NPs) have been used in a variety of cancer detection/imaging applications. Here we show that anti-FRα targeted superparamagnetic iron oxide nanoparticles (SPION) can be used for in vivo detection by two different imaging methods. Superparamagnetic Relaxometry (SPMR) is a highly sensitive in vivo detection technology that is able to differentiate the magnetic signature of nanoparticles bound to tumor cells from unbound nanoparticles. Same targeted SPIONs accumulated in tumor are able to provide molecular magnetic resonance imaging (MRI) contrast as well. Our results have shown that the anti-FRα NPs can distinguish high and low FRα expression cell lines, such as KB and A549, respectively in an in vitro cell based assay by SPMR, demonstrating good sensitivity, specificity and selectivity. In vivo study using xenograph model with KB and A549 cells implanted subcutaneously on the flank region of female athymic nude mice demonstrated higher level tumor accumulation of anti-FRα NPs in KB tumor compared to A549 tumor, measurable by ex vivo tumor detection using SPMR. Using a PEG NPs (without the target ligand) as control for the mice study have shown that minimum nanoparticle tumor accumulated were observed, demonstrating the specificity of the nanoparticles in vivo. Organ distribution study indicated that anti-FRα NPs mostly accumulated in liver and spleen as these nanoparticles were cleared through these two organs. Other organs such as brain, heart, lung, kidney didn’t show appreciable accumulation. The repeat of same type of xenograph mice model used in the SPMR study is currently under the way using MRI as an alternative in vivo detection method with images taken pre- and post- dosing of the nanoparticles. Based on the specificity and sufficient accumulation of nanoparticles demonstrated in the SPMR study, it is expected that MRI will show similar performance with additional anatomical information.Our anti-FRα NPs provided targeted and specific delivery to cancerous tissue and generated measurable signal by SPMR. Furthermore, demonstration of these anti-FRα NPs generating tumor specific contrast in MRI is currently under the way. These studies lay the groundwork for use of bio-safe magnetic particles as a detection and contrast agent for early ovarian cancer detection with improved accuracy to minimize the needs of invasive biopsies/surgery as well as potential utility for monitoring therapy response or recurrence.
Citation Format: Marie Zhang, Kathirvel Kandasamy, Yamitha Perera, Dan Inglese, Eric Smith-Nguyen. In vivo targeted detection and imaging of ovarian cancer by SPMR and MRI using anti-folate receptor functionalized iron oxide nanoparticles. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3586.