PET of EGFR Expression with an 18F-Labeled Affibody Molecule

Journal of Nuclear Medicine

Hongguang Liu¹  Song Wu¹  Zheng Miao¹  Shibo Qi¹  Gang Ren¹  Zhen Cheng¹ 

[1] Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, Stanford, California Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, Stanford, California Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, Stanford, California

关键词: Affibody;    cancer imaging;    ¹⁸F;    PET;    EGFR;   

DOI  :  10.2967/jnumed.111.100842

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Epidermal growth factor receptor (EGFR) is often overexpressed in a variety of human cancers, and its expression is associated with poor prognosis for many cancer types. However, an accurate technique to noninvasively image EGFR expression in vivo is not available in the clinical setting. In this research, an Affibody analog, anti-EGFR Ac-Cys-ZEGFR:1907, was successfully site-specifically 18F-labeled for PET of EGFR expression. Methods: The prosthetic group N-[2-(4-18F-fluorobenzamido) ethyl] maleimide (18F-FBEM) was conjugated to Ac-Cys-ZEGFR:1907 under mild conditions (pH 7) to produce the probe 18F-FBEM-Cys-ZEGFR:1907. The binding affinity and specificity tests of 18F-FBEM-Cys-ZEGFR:1907 to EGFR were conducted using A431 cancer cells. Small-animal PET and biodistribution studies were conducted on various mice tumor xenograft models with EGFR overexpression (6 types) after injection of approximately 2.0 MBq of 18F-FBEM-Cys-ZEGFR:1907 with or without coinjection of unlabeled Ac-Cys-ZEGFR:1907 for up to 3 h after injection. A correlation study between 18F-FBEM-Cys-ZEGFR:1907 small- animal PET quantification and ex vivo Western blot analysis of tumor EGFR expression was conducted in those 6 types of tumor models. Results: 18F-FBEM-Cys-ZEGFR:1907 binds to EGFR with low nanomolar affinity (37 nM) in A431 cells. 18F-FBEM-Cys-ZEGFR:1907 rapidly accumulated in the tumor and cleared from most of the normal organs except the liver and kidneys at 3 h after injection, allowing excellent tumor–to–normal tissue contrast to be obtained. In the A431 tumor xenograft model, coinjection of the PET probe with 45 μg of Ac-Cys-ZEGFR:1907 was able to improve the tumor uptake (3.9 vs. 8.1 percentage of the injected radioactive dose per gram of tissue, at 3 h after injection) and tumor imaging contrast, whereas coinjection with 500 μg of Ac-Cys-ZEGFR:1907 successfully blocked the tumor uptake significantly (8.1 vs. 1.0 percentage of the injected radioactive dose per gram of tissue, at 3 h after injection, 88% inhibition, P < 0.05). Moderate correlation was found between the tumor tracer uptake at 3 h after injection quantified by PET and EGFR expression levels measured by Western blot assay (P = 0.007, R = 0.59). Conclusion: 18F-FBEM-Cys-ZEGFR:1907 is a novel protein scaffold–based PET probe for imaging EGFR overexpression of tumors, and its ability to differentiate tumors with high and low EGFR expression in vivo holds promise for future clinical translation.

【 授权许可】

Unknown