Theranostics 2011; 1:403-412. doi:10.7150/thno/v01p0403 This volume

Research Paper

PET Imaging of Integrin Positive Tumors Using 18F Labeled Knottin Peptides

Shuanglong Liu1*, Hongguang Liu1*, Gang Ren1, Richard H. Kimura2, Jennifer R. Cochran2, Zhen Cheng1 ✉

1. Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, California, 94305-5344, USA
2. Molecular Imaging Program at Stanford (MIPS), Bio-X Program, and Department of Bioengineering, Stanford University, California, 94305-5344, USA
* S. Liu and H. Liu contributed equally to the work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Liu S, Liu H, Ren G, Kimura RH, Cochran JR, Cheng Z. PET Imaging of Integrin Positive Tumors Using 18F Labeled Knottin Peptides. Theranostics 2011; 1:403-412. doi:10.7150/thno/v01p0403. Available from

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Purpose: Cystine knot (knottin) peptides, engineered to bind with high affinity to integrin receptors, have shown promise as molecular imaging agents in living subjects. The aim of the current study was to evaluate tumor uptake and in vivo biodistribution of 18F-labeled knottins in a U87MG glioblastoma model.

Procedures: Engineered knottin mutants 2.5D and 2.5F were synthesized using solid phase peptide synthesis and were folded in vitro, followed by radiolabeling with 4-nitrophenyl 2-18F-fluoropropionate (18F-NFP). The resulting probes, 18F-FP-2.5D and 18F-FP-2.5F, were evaluated in nude mice bearing U87MG tumor xenografts using microPET and biodistribution studies.

Results: MicroPET imaging studies with 18F-FP-2.5D and 18F-FP-2.5F demonstrated high tumor uptake in U87MG xenograft mouse models. The probes exhibited rapid clearance from the blood and kidneys, thus leading to excellent tumor-to-normal tissue contrast. Specificity studies confirmed that 18F-FP-2.5D and 18F-FP-2.5F had reduced tumor uptake when co-injected with a large excess of the peptidomimetic c(RGDyK) as a blocking agent.

Conclusions: 18F-FP-2.5D and 18F-FP-2.5F showed reduced gallbladder uptake compared with previously published 18F-FB-2.5D. 18F-FP-2.5D and 18F-FP-2.5F enabled integrin-specific PET imaging of U87MG tumors with good imaging contrasts. 18F-FP-2.5D demonstrated more desirable pharmacokinetics compared to 18F-FP-2.5F, and thus has greater potential for clinical translation.

Keywords: Cystine knot peptide, RGD, Integrin, 18F, PET