Full Text | PDF

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

Research Paper

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

Shuanglong Liu^1*, Hongguang Liu^1*, Gang Ren¹, Richard H. Kimura², Jennifer R. Cochran², Zhen Cheng^{1 ✉}

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.

✉ Corresponding author: E-mail: zchengedu

Abstract

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

Citation styles

©2024 Ivyspring International Publisher. Terms of use