Preclinical characterisation of ¹¹¹In‐DTPA‐trastuzumab

Abstract

Trastuzumab (Herceptin®) is a recombinant humanised IgG1 monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), used for metastatic breast cancer treatment. Radiolabelled trastuzumab may have several future applications for diagnostic use. The aim of the present study was to develop clinical grade 111 Indium ( 111 In) radiolabelled trastuzumab, to evaluate the stability and immunoreactivity of the tracer and to perform a biodistribution study in human tumour‐bearing mice. Trastuzumab was radiolabelled with 111 In using DTPA as a chelator. 111 In‐DTPA‐trastuzumab (labelling yield 92.3±2.3%, radiochemical purity 97.0±1.5%) is stable in PBS when stored at 4°C for more than 14 days. The immunoreactive fraction determined by cell‐binding assays, using the HER2‐overexpressing human ovarian SK‐OV‐3 tumour cell line, was 0.87±0.06. Biodistribution and tumour targeting were studied in HER2 receptor‐positive and ‐negative tumour‐bearing athymic mice. The HER2‐positive tumour showed (9.77±1.14% injected dose per gram (ID g −1 )) substantial uptake of the labelled antibody already after 5 h. The difference in uptake between HER2‐positive versus ‐negative tumours was even more pronounced 3 days after injection (16.30±0.64% ID g −1 ), and was visualised by radioimmunoscintigraphy. Liver, spleen and kidney showed marked tracer uptake. In summary, trastuzumab can be efficiently radiolabelled with 111 In with high labelling yields and high stability. 111 In‐DTPA‐trastuzumab selectively binds to the human HER2 receptor both in vitro and in vivo in animals. Therefore, 111 In‐DTPA‐trastuzumab appears suitable for clinical use. British Journal of Pharmacology (2004) 143 , 99–106. doi: 10.1038/sj.bjp.0705915