This project explores a peptide nucleic acid (PNA)-based pretargeting method for radionuclide therapy and diagnosis of cancer.
A common issue in targeted radionuclide therapy is the difficulty to deliver a sufficiently high radiation dose to the tumor cells for the desired effect, without damage to healthy tissues. A safe and efficient method to reduce the accumulation of radionuclides in the healthy organs, while ensuring efficient transport and binding to the target cells, has recently been developed.
The method is based on administration of a peptide nucleic acid (PNA) probe conjugated to a tumor-targeting protein to locate and bind to the cancer cells. This is followed by treatment with a second PNA conjugate, labeled with a radionuclide and having the ability to hybridize with the first PNA conjugate.
The PNA molecules of the conjugates are engineered to increase the radioactivity in the tumor and to avoid accumulation in blood and healthy tissues. In a series of papers (see below), it has been demonstrated that PNA-based pretargeting gives significantly lower uptake of radionuclides in blood, liver and kidney, while the cancer cells are subjected to a large radiation dose.
PNA probes have advantages such as no reported immunogenicity or toxicity, high in vivo stability, high specificity, easily tunable binding strength, and well-established synthesis routes fully compatible with peptide synthesis, which allows for flexible and modular combination with different chelators, radionuclides, and other payloads. The pretargeting method based is expected to be particularly well suited for the diagnosis and treatment of solid tumors with low radiosensitivity and limited diffusion.
The pretargeting project is led by Amelie Eriksson Karlström (PI) and currently involves the group members Kristina Westerlund and Jacob Clinton.
Publications on PNA-based pretargeting from the group:
