%0 Journal Article
%T 64Cu-NODAGA-c(RGDyK) Is a Promising New Angiogenesis PET Tracer: Correlation between Tumor Uptake and Integrin Expression in Human Neuroendocrine Tumor Xenografts
%A Jytte Oxboel
%A Christina Schjoeth-Eskesen
%A Henrik H. El-Ali
%A Jacob Madsen
%A Andreas Kjaer
%J International Journal of Molecular Imaging
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/379807
%X Purpose. The purpose of this paper is to evaluate a new PET tracer 64Cu-NODAGA-c(RGDyK) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans. Procedures. Nude mice with human neuroendocrine tumor xenografts (H727) were administered 64Cu-NODAGA-c(RGDyK) i.v. for study of biodistribution as well as for dynamic PET. Gene expression of angiogenesis markers integrin , integrin , and VEGF-A were analyzed using QPCR and correlated to the tracer uptake in the tumors (%ID/g). From biodistribution data human radiation-absorbed doses were estimated using OLINDA/EXM. Results. Tumor uptake was 1.2%ID/g with strong correlations between gene expression and tracer uptake, for integrin £¿ , integrin £¿ and VEGF-A (all ). The whole body effective dose for humans was estimated to be 0.038 and 0.029£¿mSv/MBq for females and males, respectively, with highest absorbed dose in bladder wall. Conclusion. 64Cu-NODAGA-c(RGDyK) is a promising new angiogenesis PET tracer with potential for human use. 1. Introduction Angiogenesis, the formation of new blood vessels, plays an important role in tumor growth, local invasiveness, and metastatic progression. Many preclinical studies and clinical trials confirm the importance of integrin ¦ÁV¦Â3 in the process of tumor angiogenesis and metastasis [1, 2]. Integrin ¦ÁV¦Â3 is a cell adhesion molecule and is highly expressed on activated endothelial cells and tumor cells but is not expressed on resting endothelial cells and therefore specific for neoangiogenesis [3]. Several extracellular matrix (ECM) proteins like vitronectin, fibrinogen, and fibronectin interact with integrin ¦ÁV¦Â3 via the amino acid sequence Arg-Gly-Asp (RGD) [4, 5]. Vascular endothelial growth factor (VEGF-A) also plays an important role in both normal vascular tissue development and tumor neovascularization and is highly expressed in various human tumors [6, 7]. In the last few years metal PET isotopes such as 68Ga and 64Cu have gained increased interest for labeling of peptides. Both 68Ga and 64Cu are excellent alternatives to 18F. 68Ga can be obtained from an in-house commercially available 68Ge/68Ga generator. The advantage of using cyclotron produced 64Cu for PET imaging and radiotherapy is the longer half-life allowing imaging at late time points acquiring additional information [8]. A longer half-life also allows more nonspecific activity to be washed out. 64Cu can now be produced in high yield and at high specific activity on a small biomedical cyclotron. Radiolabeled RGD peptides for
%U http://www.hindawi.com/journals/ijmi/2012/379807/