Abstract B045: In vivo ovarian cancer detection using folate receptor-α targeted iron oxide nanoparticles
Authors: Zhang Marie , Perera Yamitha , Kandasamy Kathirvel , Inglese Dan 
Published: March 2024

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. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used in a variety of cancer detection/imaging applications, including Magnetic Resonant Imaging (MRI), Magnetic Particle Imaging (MPI) as well as Superparamagnetic Relaxometry (SPMR) detection currently being developed in-house. SPMR is a highly sensitive detection technology that can differentiate the magnetic signature of nanoparticles bound to tumor cells from unbound nanoparticles (NP). Folate receptor alpha (FRα) is a folate transporter overexpressed in approximately 90% of ovarian cancer, which makes it a suitable molecular target to use in developing tumor imaging methods. Our earlier study using xenograft model with KB (FRα +ve) and A549 (FRα -ve) cells implanted subcutaneously on the flank region of female athymic nude mice demonstrated higher level tumor accumulation of folate-NPs in KB tumor compared to A549 tumor, detectable by SPMR and MRI. To translate such results into a potential clinical application, we recently generated two orthotopic mice ovarian cancer models by implanting KB cells surgically into ovary as well intraperitoneally (IP) into mice abdominal cavity (metastasis model). Implanted tumor cells were allowed to grow for about 2 weeks. Folate-NPs (20mg Fe/kg) were delivered via tail vein or IP injections. PEG-NPs were also delivered as controls. Mice were euthanized 24-hour post-dosing. Mesenteric tumor tissue and reproductive organs with tumors were resected and measured on SPMR. Same tissues from mice without NP injection or with PEG-NP injection were also measured. Our results demonstrated that Folate-NPs reached the tumor sites in both orthotopic models and accumulated specifically at high level detectable by SPMR ex vivo. The amount of NP accumulation in mice with orthotopically implanted tumor was 3x-10x more than those of the xenograft subcutaneous flank implanted tumor model, indicating efficient NP delivery and binding of NP with tumor cells in its natural tissues/organs. The repeat studies of these orthotopic mice models used in the SPMR experiment are currently being conducted using MRI as an alternative in vivo detection method with images taken pre- and post- dosing of the NPs. We anticipate that folate-NPs presence in the tumors will be easily observable on MRI images as it produces T2 contrast along with additional anatomical information. Favorable orthotopic mice model results presented here will lay the groundwork for IND-enabling development of these targeted NP as T2 contrast agent for early ovarian cancer detection using MRI. This type of targeted imaging technology will improve the accuracy of cancer detection in vivo without the use of radioisotopes or radiation, therefore, minimize the needs of invasive biopsies/surgery, with further potential of monitoring therapy response or recurrence.

Citation Format: Marie Zhang, Yamitha Perera, Kathirvel Kandasamy, Dan Inglese. In vivo ovarian cancer detection using folate receptor-α targeted iron oxide nanoparticles [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B045.