Academic Journals Database
Disseminating quality controlled scientific knowledge

PET Imaging of EGFR expression in nude mice bearing MDA-MB-468, human breast cancer using 64Cu-DOTA-Cetuximab

ADD TO MY LIST
 
Author(s): Kayvan Sadri | Kaijun Zhang | Deva Kumar | Qing Ren | Urich Rodeck | Mathew Thakur

Journal: Iranian Journal of Nuclear Medicine
ISSN 1681-2824

Volume: 18;
Issue: Suppl 1;
Start page: 50;
Date: 2010;
Original page

Keywords: EGFR | Cetuximab | Copper | PET

ABSTRACT
Introduction: EGFR is a transmembrane protein related to the tyrosine kinase receptor family. An increased expression of EGFR is the hallmark of many human tumors, such as breast cancer, squamous-cell carcinoma of the head and neck, and prostate cancer. Cetuximab (C225, ErbituxR, an IgG1 class) targeting the EGFR is the first mAb targeted against EGFR receptors approved by the FDA for metastatic colorectal carcinoma. The overall goal of this study was to evaluate 64Cu labeled DOTA-Cetuximab to image EGFR positive breast cancer in athymic nude mice bearing MDA-MB-468. Methods: Cetuximab was conjugated with DOTA, purified by molecular filtration and concentration was determined spectrophotometrically. DOTA-Cetuximab was labeled with 64Cu and radiochemical yield was determined by HPLC. The binding affinity of 64Cu - DOTA-Cetuximab to MDA-MB-468 was determined in the presence of 0.05-10 nM of unlabeled Cetuximab. The athymic nude mice bearing MDA-MB-468 (~5×106) xenografts were given, 64Cu - DOTA-Cetuximab i.v., (50 ± 6.1 μCi, 4 hr group, n=5, 200 ± 22.7 μCi, 24 hr group, n=5). Animals were then imaged, sacrificed and quantitative tissue distribution was performed. In order to assess tumor uptake is mediated by EGFR-receptors expression, biodistribution study was done with blocking unlabeled Cetuximab. Results: The radiochemical yield was 97.1 ± 1.1% with the specific activity of 923 Ci/mM Cetuximab. 64Cu - DOTA-Cetuximab showed high affinity to EGFR-positive MB-468 cells (KD of 0.4 nM). Both biodistribution and microPET imaging studies with 64Cu - DOTA-Cetuximab demonstrated higher tumor uptake at 24 hr (21.91% ± 0.86% ID/g) as compare to at 4 hr (12.33% ± 0.41% ID/g). Excellent PET images were obtained. Conclusion: 64Cu - DOTA-Cetuximab is worthy of further investigation to target EGFR for imaging breast cancer
Why do you need a reservation system?      Save time & money - Smart Internet Solutions