Novel pretargeted radionuclide therapy for HER2-expressing cancers shows promise

July 02, 2018

RESTON, VA - In a mouse model, researchers have demonstrated that a novel, affibody-based pretargeted radionuclide therapy for HER2 (human epidermal growth factor receptor 2)-expressing cancers is non-toxic to the kidneys and improves survival. The study is reported in The Journal of Nuclear Medicine's July featured article of the month.

"Affibody molecules, small proteins engineered to bind to specific tumor-associated target proteins, have demonstrated excellent features for targeted molecular imaging, but their application for radionuclide therapy has so far been prevented by high renal reabsorption," explains Vladimir Tolmachev, DMSc, professor at Uppsala University in Uppsala, Sweden. "We have now shown that the use of peptide nucleic acid (PNA)-mediated pretargeting enables a safe application of affibody molecules for radionuclide therapy."

For the study, affibody-pretargeted lutetium-177 (177Lu)-labeled PNA was tested and evaluated in mice bearing HER2-expressing xenografts. Experimental radionuclide therapy of the mice was performed in six cycles separated by 7 days.

The data showed very rapid clearance of 177Lu-PNA from most tissues. The only tissues with prominent uptake were the kidneys and tumor, however, tumor uptake was four-fold higher than renal uptake at one hour post-injection. In addition, 84 percent of the renal uptake cleared with a 15-minute half-life, whereas the tumor clearance half-life was 63 hours.

Results demonstrate that this pretargeting system can deliver an absorbed dose to tumors that appreciably exceeds the dose to critical organs, making affibody-based PNA-mediated pretargeted radionuclide therapy highly attractive.

Marion de Jong, PhD, professor at Erasmus MC in Rotterdam, The Netherlands, states, "The safe application of radiolabeled affibody molecules for radionuclide therapy in patients will open up a whole new world of therapeutic options, as affibody molecules are excellent targeting moieties and can be generated for a wide range of targets."

de Jong adds, "More specifically regarding anti-HER2 applications, the pretargeted affibody-based anti-HER2 might be used for treatment of patients who developed resistance to trastuzumab or other HER2-targeting therapies. Such resistance might be accompanied by preserved high expression of HER2."

Amelie Eriksson Karlström, PhD, professor at KTH Royal Institute of Technology in Stockholm, Sweden, points out additional advantages to using an affibody molecule as the pretargeting vector, explaining, "Production of affibody molecules is much cheaper than the production of antibodies. This might make our constructs more affordable and available."

She adds, "Another important feature of our approach is the modular design of the construct. The Sortase A-mediated coupling can easily be used for the conjugation of an affibody molecule with specificity to a different target or even another class of targeting scaffold protein. Labelsare not limited to 177Lu; probes could also be labeled with the alpha-emitting nuclides actinium-225 (225Ac) or thorium-227 (227Th), or a positron-emitting nuclide such as gallium-68 (68Ga) for theranostics (both diagnosis and therapy). We anticipate that this study is a first step in the validation of a versatile pretargeting platform."
Authors of "Radionuclide therapy of HER2-expressing human xenografts using an affibody molecule-based PNA-mediated pretargeting: in vivo proof-of-principle" include Kristina Westerlund, and Amelie Eriksson Karlström, KTH Royal Institute of Technology, Stockholm, Sweden; Mohamed Altai, Bogdan Mitran, Maryam Oroujeni, Christina Atterby, Anna Orlova, Johanna Mattsson, Patrick Micke, and Vladimir Tolmachev, Uppsala University, Uppsala, Sweden; and Mark Konijnenberg and Marion de Jong, Erasmus MC, Rotterdam, The Netherlands.

This research was financially supported by grants from the Swedish Cancer Society, the Swedish Research Council, ProNova VINN Excellence Centre for Protein Technology, and the Swedish Agency for Innovation (VINNOVA).

Please visit the SNMMI Media Center to view the PDF of the study, including images, and more information about molecular imaging and personalized medicine. To schedule an interview with the researchers, please contact Laurie Callahan at (703) 652-6773 or Current and past issues of The Journal of Nuclear Medicine can be found online at


The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging, vital elements of precision medicine that allow diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes.

SNMMI's more than 16,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit

Society of Nuclear Medicine and Molecular Imaging

Related Tumor Articles from Brightsurf:

New cancer diagnostics: A glimpse into the tumor in 3D
A new technique could initiate a revolution in pathology: Tumor tissue is made transparent and illuminated with a special ultramicroscope.

Tumor progression depends on the tumor microenvironment
Researchers from Tokyo Medical and Dental University (TMDU) and Niigata University identified a novel mechanism by which tumors progress.

How do tumor cells divide in the crowd?
Scientists led by Dr. Elisabeth Fischer-Friedrich, group leader at the Excellence Cluster Physics of Life (PoL) and the Biotechnology Center TU Dresden (BIOTEC) studied how cancer cells are able to divide in a crowded tumor tissue and connected it to the hallmark of cancer progression and metastasis, the epithelial-mesenchymal transition (EMT).

Finding a way to STING tumor growth
The immune protein STING has long been noted for helping protect against viruses and tumors by signaling a well-known immune molecule.

Assembly within the tumor center
Number of macrophages in tumor tissue enables prognosis of lung tumor progression.

Mirror image tumor treatment
Our immune system ought to be able to recognize and kill tumor cells.

Traces of immortality in tumor DNA
To gain an infinite lifespan, cancer cells need to maintain the ends of their chromosomes, known as telomeres.

Peering into the genome of brain tumor
Scientists at Osaka University have created a machine learning method for classifying the mutations of glioma brain tumors based on MR images alone.

Glutamine-blocking drug slows tumor growth and strengthens anti-tumor response
A compound developed by Johns Hopkins researchers that blocks glutamine metabolism can slow tumor growth, alter the tumor microenvironment and promote the production of durable and highly active anti-tumor T cells.

Cancer genes and the tumor milieu
In a recent study published in Cancer Research, researchers demonstrate the role of an oncogene in altering the immediate environment of tumors.

Read More: Tumor News and Tumor Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to