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. 2013 Nov;2(4):10.1016/j.coche.2013.08.009.
doi: 10.1016/j.coche.2013.08.009.

Alternative Non-Antibody Protein Scaffolds for Molecular Imaging of Cancer

Lawrence A Stern  1 , Brett A Case  1 , Benjamin J Hackel  1
Affiliations

Alternative Non-Antibody Protein Scaffolds for Molecular Imaging of Cancer

Lawrence A Stern et al. Curr Opin Chem Eng. 2013 Nov.

Abstract

The development of improved methods for early detection and characterization of cancer presents a major clinical challenge. One approach that has shown excellent potential in preclinical and clinical evaluation is molecular imaging with small-scaffold, non-antibody based, engineered proteins. These novel diagnostic agents produce high contrast images due to their fast clearance from the bloodstream and healthy tissues, can be evolved to bind a multitude of cancer biomarkers, and are easily functionalized by site-specific bioconjugation methods. Several small protein scaffolds have been verified for in vivo molecular imaging including affibodies and their two-helix variants, knottins, fibronectins, DARPins, and several natural ligands. Further, the biodistribution of these engineered ligands can be optimized through rational mutation of the conserved regions, careful selection and placement of chelator, and modification of molecular size.

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Figures

Figure 1
Figure 1
Schematic for molecular imaging agent development. Several scaffolds have been validated for in vivo molecular imaging. Selection of an appropriate scaffold, followed by directed evolution – for binding and delivery characteristics – and radiolabeling yield an imaging agent with potent delivery and retention properties capable of producing high contrast molecular images.
Figure 2
Figure 2
Cartoon structure with surface representation of protein scaffolds used in molecular imaging applications. Variable regions are highlighted in red. Conserved portions are shown in grey. A: affibody (PDB: 2B88); B: knottin (1HYK); C: fibronectin (1TTF); D: two-helix affibody (modified from three-helix affibody 2KZJ); E: DARPin (2JAB); F: natural ligand (EGF) (2KV4).
Figure 3
Figure 3
Female BALB/c nu/nu mice with HER2-expressing NCI-N87 xenografts were imaged via PET using 124I-PIB-ZHER2:342 affibody (A-C) and 124I-PIB-trastuzumab (D-F). Mice were sacrificed and imaged 6 (A and D), 24 (B and E), and 72 h (C and F) post injection. Urinary bladders were removed before scanning. Figure reproduced.[10]
See this image and copyright information in PMC

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