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Evaluation of an Affibody-Based Binder for Imaging of Immune Check-Point Molecule B7-H3
Maryam Oroujeni1,2, Ekaterina A Bezverkhniaia3,4, Tianqi Xu1
1Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden.
Abstract:
Radionuclide molecular imaging could provide an accurate assessment of the expression of molecular targets in disseminated cancers enabling stratification of patients for specific therapies. B7-H3 (CD276) is a transmembrane protein belonging to the B7 superfamily. This protein is overexpressed in different types of human malignancies and such upregulation is generally associated with a poor clinical prognosis. In this study, targeting properties of an Affibody-based probe, AC12, containing a -GGGC amino acid sequence as a chelator (designated as AC12-GGGC) labelled with technetium-99m (99mTc) were evaluated for imaging of B7-H3-expressing tumours. AC12-GGGC was efficiently labelled with 99mTc. [99mTc]Tc-AC12-GGGC bound specifically to B7-H3 expressing cells in vitro with affinities in nanomolar range. In mice bearing B7-H3-expressing xenografts, [99mTc]Tc-AC12-GGGC showed tumour uptake of 2.1 ± 0.5 %ID/g at 2 h after injection. Its clearance from blood, normal organs and tissues was very rapid. This new targeting agent, [99mTc]Tc-AC12-GGGC, provided high tumour-to-blood ratio already at 2 h (8.2 ± 1.9), which increased to 11.0 ± 0.5 at 4 h after injection. Significantly (p < 0.05) higher tumour-to-liver and higher tumour-to-bone ratios at 2 h in comparison with 4 h after injection were observed. Thus, [99mTc]Tc-AC12-GGGC could be a promising candidate for further development.
Insights
A new technetium-99m labeled Affibody probe, [99mTc]Tc-AC12-GGGC, shows promise for molecular imaging. It effectively targets B7-H3 expressing tumors, enabling better patient stratification for cancer therapies.
Area of Science:
- Nuclear medicine
- Molecular imaging
- Oncology
Background:
- B7-H3 (CD276) is overexpressed in many cancers and linked to poor prognosis.
- Molecular imaging aids in assessing cancer targets and patient stratification for targeted therapies.
Purpose of the Study:
- To evaluate the targeting and imaging properties of a novel technetium-99m labeled Affibody probe, [99mTc]Tc-AC12-GGGC, for B7-H3-expressing tumors.
Main Methods:
- An Affibody-based probe, AC12-GGGC, was labeled with technetium-99m (99mTc).
- In vitro binding affinity to B7-H3 expressing cells was assessed.
- In vivo studies were conducted in mice with B7-H3 xenografts to evaluate tumor uptake and biodistribution.
Main Results:
- [99mTc]Tc-AC12-GGGC demonstrated efficient labeling and specific binding to B7-H3 positive cells.
- The probe showed rapid clearance from blood and normal tissues with significant tumor uptake (2.1 ± 0.5 %ID/g at 2h).
- High tumor-to-blood ratios were achieved early (8.2 ± 1.9 at 2h, increasing to 11.0 ± 0.5 at 4h), with favorable tumor-to-organ ratios.
Conclusions:
- [99mTc]Tc-AC12-GGGC is a promising radiotracer for molecular imaging of B7-H3-expressing tumors.
- Its rapid pharmacokinetics and high tumor targeting suggest potential for clinical development in cancer patient stratification.
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