Loading...
Please wait, while we are loading the content...
Pretargeted Alpha Therapy of Disseminated Cancer Combining Click Chemistry and Astatine-211.
| Content Provider | Europe PMC |
|---|---|
| Author | Timperanza, Chiara Jensen, Holger Bäck, Tom Lindegren, Sture Aneheim, Emma |
| Editor | Velikyan, Irina |
| Copyright Year | 2023 |
| Abstract | To enhance targeting efficacy in the radioimmunotherapy of disseminated cancer, several pretargeting strategies have been developed. In pretargeted radioimmunotherapy, the tumor is pretargeted with a modified monoclonal antibody that has an affinity for both tumor antigens and radiolabeled carriers. In this work, we aimed to synthesize and evaluate poly-L-lysine-based effector molecules for pretargeting applications based on the tetrazine and trans-cyclooctene reaction using 211At for targeted alpha therapy and 125I as a surrogate for the imaging radionuclides 123, 124I. Poly-L-lysine in two sizes was functionalized with a prosthetic group, for the attachment of both radiohalogens, and tetrazine, to allow binding to the trans-cyclooctene-modified pretargeting agent, maintaining the structural integrity of the polymer. Radiolabeling resulted in a radiochemical yield of over 80% for astatinated poly-L-lysines and a range of 66–91% for iodinated poly-L-lysines. High specific astatine activity was achieved without affecting the stability of the radiopharmaceutical or the binding between tetrazine and transcyclooctene. Two sizes of poly-L-lysine were evaluated, which displayed similar blood clearance profiles in a pilot in vivo study. This work is a first step toward creating a pretargeting system optimized for targeted alpha therapy with 211At. |
| Volume Number | 16 |
| PubMed Central reference number | PMC10145095 |
| Issue Number | 4 |
| PubMed reference number | 37111352 |
| Journal | Pharmaceuticals (Basel) |
| e-ISSN | 14248247 |
| DOI | 10.3390/ph16040595 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2023-04-15 |
| Access Restriction | Open |
| Rights License | Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors. |
| Subject Keyword | astatine-211 targeted alpha therapy pretargeting click chemistry radioimmunotherapy radionuclide therapy drug design radiopharmaceuticals theranostics |
| Content Type | Text |
| Resource Type | Article |
| Subject | Drug Discovery Pharmaceutical Science Molecular Medicine |
