A Targeted Alpha-Particle Radiopharmaceutical for Bone Metastatic Breast Cancer
Abstract
The proposed studies will develop and evaluate a new therapeutic strategy for treating breast cancer bone metastasis by disrupting the interactions between breast cancer cells and sensory neurons within bone using alpha particle-emitting radiopharmaceuticals that target the CGRP-CRLR axis. The successful completion of this project will establish a new therapeutic target for cancer-induced bone pain and bone metastatic breast cancer; while providing the foundation required to develop new therapies that will decrease suffering and improve survival of breast cancer patients with bone metastases. During the entire grant period, (i) we further validated that CRLR is a suitable target to treat bone metastatic breast cancer and successfully manipulated CRLR levels in breast cancer cells using lenti-virus technique; (ii) we validated that CRLC-overexpressing breast cancer cells can grow in vivo without affecting growth rate; (iii) we prepared the PTCA-CGRP27-37 peptides and completed the radiochemistry experiments with the PCTA-CGRP27-37 peptides and developed strategies to overcome the severe lipophilicity of the agents under investigation; and (iv) we completed the preparation and stability analysis of several new ligands using the positron emitting radioisotope zirconium-89 (89Zr: t = 78.4 h, Beta+: 22.8 percent, Ebeta+max = 901 keV; EC: 77 percent, Egamma = 909 keV; 99 percent).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1215420
Entities
People
- Thaddeus J Wadas
- Yusuke Shiozawa
Organizations
- University of Iowa
- Wake Forest University