Preclinical Positron Emission Tomography Imaging of B7–H3 Expression Using Affibody Molecules Labeled with Gallium-68
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Affibody molecules, nonimmunoglobulin scaffold proteins, have a high potential as probes for molecular imaging of different molecular targets. One of the molecular targets for radionuclide diagnosis and therapy is B7–H3 (known as CD276), which is overexpressed in various cancers, whereas its expression is low in most normal organs and tissues. The visualization of expression levels of B7–H3 has been performed using Affibody molecules labeled with Tc-99m. However, radionuclide molecular imaging using PET offers several advantages such as superior sensitivity, quantitation accuracy, and better spatial resolution compared to SPECT. In this study, we aimed to introduce a radiotracer for PET imaging of B7–H3. To design imaging agents for labeling with the generator-produced positron-emitting radionuclide 68 Ga, the macrocyclic triaza chelator (2-[4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl]acetic acid) (NOTA) was site-specifically coupled to the C-terminal cysteine of the anti–B7-H3 Affibody molecules. Four different variants of Affibody molecules, Z B7–H3 _ 2, Z B7–H3 _ 3, Z B7–H3 _ 4, and Z AC12 (as control), were produced, characterized, and successfully labeled with 68 Ga. 68 Ga-labeled conjugates bound specifically to B7–H3-expressing cells in vitro and in vivo . Biodistribution showed that [ 68 Ga]Ga-Z B7–H3 _ 2 had the highest tumor accumulation only 2 h after administration, which was 2.8-fold higher than that for the control Z AC12 . There was a tendency for higher tumor-to-organ ratios compared to the other variants, resulting in higher imaging contrast using [ 68 Ga]Ga-Z B7–H3 _ 2 for preclinical PET imaging of B7–H3-expressing tumors. Thus, [ 68 Ga]Ga-Z B7–H3 _ 2 could be a promising candidate for further development aimed at clinical PET in the future.
Institutions: Uppsala University, Affibody (Sweden)
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G1152396210, Combined targeted radionuclide imaging and targeted therapy – a way for precision treatment of prostate cancer, G2768960689, G2878354728, G3551410381, G356405547, CEASE cancer: CarcinoEmbryonic Antingen-targeting Scaffold protein Engineering for precision targeted therapy of carcinomas, G6281963324
OpenAlex ID: W4414029204