Preparation, biological evaluation, and pharmacokinetics of the human anti-HER1 monoclonal antibody panitumumab labeled with 86Y for quantitative PET of carcinoma.
Preparation, biological evaluation, and pharmacokinetics of the human anti-HER1 monoclonal antibody panitumumab labeled with 86Y for quantitative PET of carcinoma.
复制标题
DOI：
10.2967/jnumed.109.071290
复制
发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Brechbiel MW
中科院分区：
文献类型：
--
作者：
Nayak TK;Garmestani K;Baidoo KE;Milenic DE;Brechbiel MW
Panitumumab, a human monoclonal antibody (mAb) that binds to the epidermal growth factor receptor (EGFR/HER1), was approved by the FDA in 2006 for the treatment of patients with HER1-expressing carcinoma. In this report, we describe preclinical development of 86Y-CHX-A″-DTPA-panitumumab for quantitative positron emission tomography (PET) imaging of HER1-expressing carcinoma. Panitumumab was conjugated to CHX-A″-DTPA and radiolabeled with 86Y. In vivo biodistribution, PET imaging, blood clearance, area under the curve (AUC), area under the moment curve (AUMC) and mean residence time (MRT) were determined on mice bearing HER1-expressing human colorectal (LS-174T), prostate (PC-3) and epidermoid (A431) tumor xenografts. Receptor-specificity was demonstrated by co-injection of 0.1 mg panitumumab with the radioimmunoconjugate (RIC). 86Y-CHX-A″-DTPA-panitumumab was routinely prepared with a specific activity exceeding 2 GBq/mg. Biodistribution and PET imaging studies demonstrated high HER1-specific tumor uptake of the RIC. In mice bearing LS-174T, PC-3 or A431 tumors, the tumor uptake at 3 d were 34.6 ± 5.9, 22.1± 1.9 and 22.7 ± 1.7 % ID/g, respectively. The corresponding tumor uptake in mice co-injected with 0.1 mg panitumumab was 9.3 ± 1.5, 8.8 ± 0.9 and 10.0 ± 1.3 % ID/g, respectively at the same time point, demonstrating specific blockage of the receptor. Normal organ and tumor uptake quantified by PET were closely related (r2= 0.95) to values determined by biodistribution studies. LS-174T tumor had the highest AUC (96.8 ± 5.6 %ID.d.g−1) and AUMC (262.5 ± 14.9 %ID.d2.g−1), however the tumor MRT were identical for all three tumors (2.7–2.8 d). This study demonstrates the potential of 86Y-CHX-A″-DTPA-panitumumab for quantitative non-invasive PET imaging of HER1-expressing tumors, and represents the first step towards clinical translation.
