Alternative non-antibody protein scaffolds for molecular imaging of cancer

Lawrence A. Stern, Brett A. Case, Benjamin J. Hackel

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations


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, designed ankyrin repeat proteins (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.

Original languageEnglish (US)
Pages (from-to)425-432
Number of pages8
JournalCurrent Opinion in Chemical Engineering
Issue number4
StatePublished - Nov 2013

Bibliographical note

Funding Information:
This work was funded by the National Institutes of General Medical Science Biotechnology Training Grant (L.A.S.) and the University of Minnesota .

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