Peptide-based probes for targeted molecular imaging

Abstract

Targeted molecular imaging techniques have become indispensable tools in modern diagnostics because they provide accurate and specific diagnosis of disease information. Conventional nonspecific contrast agents suffer from low targeting efficiency; thus, the use of molecularly targeted imaging probes is needed depending on different imaging modalities. Although recent technologies have yielded various strategies for designing smart probes, utilization of peptide-based probes has been most successful. Phage display technology and combinatorial peptide chemistry have profoundly impacted the pool of available targeting peptides for the efficient and specific delivery of imaging labels. To date, selected peptides that target a variety of disease-related receptors and biomarkers are in place. These targeting peptides can be coupled with the appropriate imaging moieties or nanoplatforms on demand with the help of sophisticated bioconjugation or radiolabeling techniques. This review article examines the current trends in peptide-based imaging probes developed for in vivo applications. We discuss the advantage of and challenges in developing peptide-based probes and summarize current systems with respect to their unique design strategies and applications.

Figure 1

A general schematic diagram of peptide-based probes for targeted molecular imaging.

Figure 2

A) Chemical structure of NOTA-Glu-[Gly-Gly-Gly-cyclo(RGDfK)]₂. B) Coronal PET images of the U87MG tumor bearing mouse at 30, 60 and 120 min without and with blocking dose of cyclo(RGDyK) after injection of ⁶⁸Ga-NOTA-Glu-[Gly-Gly-Gly-cyclo(RGDfK)]₂. Modified with permission from ref. . Copyright 2009, Springer-Varlag.

Figure 3

A dark-quenched activatable MMP-13 probe. A) The molecular surface of human MMP-13 and the modeled binding pockets of the MMP-13 imaging probe. Arrow and italics indicate the cleavage site. B) Schematic diagram of activation process. C) In vivo imaging of overexpressed MMP-13 in normal, six and eight week osteoarthritis (OA)-induced cartilages 1 h after intracartilage-injection of the MMP-13 imaging probe. Arrows; dotted line (normal) and solid line (OA). Modified with permission from ref. . Copyright 2008, American Chemical Society.

Figure 4

A) Schematic diagram of CTX peptide conjugation to polyethylene (PEG) coated iron oxide nanoparticles (IONPs). B) TEM images of 9L cells with IONPs a) without and b) with CTX peptides. C) MRI anatomical image of a mouse bearing 9L xenograft tumor. a) Anatomical image in the sagittal plane displaying the location of the tumor (the arrow marks the tumor location). Changes in R2 relaxivity values for the tumor regions, superimposed over anatomical MR images, for mouse receiving IONPs b) without and with CTX peptides after 3 h post injection. Modified with permission from ref. . Copyright 2008, Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.

Figure 5

A) Schematic diagram of QD750-PEG_2k-RGD. B) In vitro staining of human breast MCF and human glioblastoma U87MG cells (low and high integrin α_vβ₃ expression, respectively) using QD750-PEG_2k-RGD. C) In vivo NIR fluoresnce imaging of U87MG tumor bearing mice (left shoulder, pointed by white arrows) injected with QD750-PEG_2k-RGD (left ) and QD750-PEG_2k (right), respectively. Modified with permission from ref. . Copyright 2006, American Chemical Society.

Figure 6

A) Schematic diagram of an integrin α_vβ₃ targeting ⁶⁴Cu-DOTA-IONP-RGD PET/MRI dual-modality probe. B) A 2D projection PET image of a mouse bearing U87MG tumor at 4 h post-injection of the probe. T2-weighted MR images of mice (the arrow indicates the tumor) C) before and D) 4 h after intravenous injection of the probe. Modified with permission from ref. . Copyright 2008, by the Society of Nuclear Medicine, Inc.