Development of 5D3 mAb and USPIO-Based Theranostics for Image-Guided Prostate Cancer Therapy
Abstract
Aggressive prostate cancers overexpress prostate-specific membrane antigen (PSMA), and we target PSMA to deliver the drug to cancer cells. We are using new PSMA-targeting 5D3 antibody in this image-guided drug development. This antibody has higher binding capabilities with PSMA than other existing PSMA-targeting antibodies. Ultra-small superparamagnetic iron oxide (USPIO) nanoparticles are biocompatible and have a high loading capacity for molecules. Since USPIO is an MRI contrast agent, drug delivery and tumor uptake can be detected with MRI. Our purpose is to synthesize, characterize, and test this new system in prostate cancer cells and mouse models of human prostate cancer and using the simultaneous PET-MRI imaging system to evaluate the drug delivery to the tumor and early tumor response to the therapy. We have conjugated the surface of the USPIO with a 5D3 mAb. This complex will be loaded with mertansine (DM1), an anti-tubulin drug molecule. These drug delivery systems are called nano-theranostics since this system has both therapeutic and image-guided diagnostic capabilities. During the first year of the project, we conjugated USPIO with 5D3 monoclonal antibody and developed USPIO-5D3 targeted drug delivery platform. It was loaded with DM1 drug molecules and labeled with imaging agents. We have successfully accomplished the development of USPIO-5D3-DM1 nano-theranostics and validate them by in vitro binding affinity studies. In vivo biodistribution study of USPIO-5D3-DM1 in mouse models shows high tumor uptake of nano-theranostics by PSMA(+) tumors by Xenogen in vivo optical imaging. These results were also confirmed by 9.4T MRI showing reduction in T2 contract. Fine tuning of the antibody and drug loading and optimization are yet to be done.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2021
- Accession Number
- AD1148574
Entities
People
- Catherine Foss
- Dmitri Artemov
- Sudath Hapuarachchige
Organizations
- Johns Hopkins University