Abstract
Affibody molecules are small (58 amino acids) engineered scaffold proteins that can be selected to bind to a large variety of proteins with a high affinity. Their small size and high affinity make them attractive as targeting vectors for molecular imaging. High-affinity affibody binders have been selected for several cancer-associated molecular targets. Preclinical studies have shown that radiolabeled affibody molecules can provide highly specific and sensitive imaging on the day of injection; however, for a few targets, imaging on the next day further increased the imaging sensitivity. A phase I/II clinical trial showed that 68Ga-labeled affibody molecules permit an accurate and specific measurement of HER2 expression in breast cancer metastases. This paper provides an overview of the factors influencing the biodistribution and targeting properties of affibody molecules and the chemistry of their labeling using positron emitters.
Highlights
Radionuclide molecular imaging permitting non-invasive quantitative visualization of molecular targets is an attractive alternative to biopsy-based methods for stratifying patients for targeted therapies [1]
The use of positron emission tomography (PET) is a preferable method for molecular imaging because it provides a better spatial resolution, registration efficiency, and accuracy of activity quantification compared to single photon emission computed tomography (SPECT) [2]
Accumulated clinical experience has enabled the identification of several major issues in the routine clinical use of full-length immunoglobulin G (IgG) as imaging probes; these issues include slow extravasation and accumulation in tumors, slow clearance from blood and unspecific compartments, and unspecific uptake in target-negative tumors due to the enhanced permeability and retention (EPR)
Summary
Radionuclide molecular imaging permitting non-invasive quantitative visualization of molecular targets is an attractive alternative to biopsy-based methods for stratifying patients for targeted therapies [1]. The most common approach used to visualize molecular targets is immunoPET, which is a methodology based on the labeling of therapeutic monoclonal antibodies with long-lived positron emitting nuclides, including 64 Cu (T 1 = 12.7 h), 89 Zr (T 1 = 78.4 h), and 124 I (T 1 = 100.2 h) [3,4] The feasibility of such an approach has been demonstrated in a number of clinical studies [5,6,7]. Mathematical modeling predicts that a further size reduction would enable an increase in tumor single-domain antibody (sdAb) with a molecular weight of 12–15 kDa permits the development of accumulation if the affinity of imaging probes high enough [11,12]. Of Mathematical modeling predicts that a further size reduction would enable an increase tumor high-affinity immunoglobulin-based targeting probes smaller than a sdAb remains very in challenging. This is Protein-Based possible using engineered non-immunoglobulin scaffold proteins [13]
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