Skip to main content
To KTH's start page To KTH's start page

PNA-based Pretargeting

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.

PNA pretargeting

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:

Oroujeni, M., Tano, H., Vorobyeva, A., Liu, Y., Vorontsova, O., Xu, T., Westerlund, K., Orlova, A., Tolmachev, V. & Eriksson Karlström, A. (2021) ”Affibody-mediated PNA-based pretargeted co-treatment improves survival of trastuzumab-treated mice bearing HER2-expressing xenografts”, J. Nucl. Med., in press.

Tano, H., Oroujeni, M., Vorobyeva, A., Westerlund, K., Liu, Y., Xu, T., Vasconcelos, D., Orlova, A., Eriksson Karlström, A. & Tolmachev, V. (2021) “Comparative evaluation of novel 177Lu-labeled PNA probes for affibody-mediated PNA-based pretargeting”, Cancers, 13, 500.

Myrhammar, A., Vorobyeva, A., Westerlund, K., Yoneoka, S., Orlova, A., Tsukahara, T., Tolmachev, V., Eriksson Karlström, A. & Altai, M. (2020) “Evaluation of an antibody-PNA conjugate as a clearing agent for antibody-based PNA-mediated radionuclide pretargeting”, Sci. Rep., 10, 20777.

Westerlund, K., Vorobyeva, A., Mitran, B., Orlova, A., Tolmachev, V., Eriksson Karlström, A. & Altai, M. (2019) ”Site-specific conjugation of recognition tags to trastuzumab for peptide nucleic acid-mediated radionuclide HER2 pretargeting”, Biomaterials, 203, 73-85.

Vorobyeva, A., Westerlund, K., Mitran, B., Altai, M., Rinne, S., Sörensen, J., Orlova, A., Tolmachev, V. & Eriksson Karlström, A. (2018) “Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy”, Sci. Rep., 8, 9643.

Westerlund, K., Altai, M., Mitran, B., Konijnenberg, M., Oroujeni, M., Atterby, C., de Jong, M., Orlova, A., Mattsson, J., Micke, P., Eriksson Karlström, A. & Tolmachev, V. (2018) “Radionuclide therapy of HER2-expressing human xenografts using an affibody molecule-based PNA-mediated pretargeting: in vivo proof-of-principle”, J. Nucl. Med., 59, 1092-1098.

Altai, M., Westerlund, K., Velletta, J., Mitran, B., Honarvar, H. & Eriksson Karlström, A. (2017) “Evaluation of affibody molecule-based PNA-mediated radionuclide pretargeting: development of an optimized conjugation protocol and 177Lu labeling”, Nucl. Med. Biol., 54, 1-9.

Honarvar, H., Westerlund, K., Altai, M., Sandström, M., Orlova, A., Tolmachev, V. & Eriksson Karlström, A. (2016) “Feasibility of Affibody molecule-based PNA-mediated radionuclide pretargeting of malignant tumors”, Theranostics, 6, 93-103.

Westerlund, K., Honarvar, H., Tolmachev, V. & Eriksson Karlström, A. (2015) “Design, preparation and characterization of PNA-based hybridization probes for Affibody molecule-mediated pretargeting”, Bioconjug. Chem., 26, 1724-1736.