Preclinical characterisation of ¹¹¹In‐DTPA‐trastuzumab

Abstract

In using DTPA as a chelator. In-DTPAtrastuzumab (labelling yield 92.372.3%, radiochemical purity 97.071.5%) is stable in PBS when stored at 41C 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 0.8770.06. Biodistribution and tumour targeting were studied in HER2 receptor-positive and -negative tumour-bearing athymic mice. The HER2-positive tumour showed (9.7771.14% injected dose per gram (ID g À1 )) 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 (16.3070.64% ID g À1 ), 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. 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.

Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with 18F-Labeled Affibody Molecule ZHER2:2395 in a Mouse Model for Ovarian Cancer

“…For example, radiolabeled trastuzumab and pertuzumab have been used for SPECT and PET of HER2 expression (13,14,16,31). However, these large proteins are characterized by slow tumor penetration and clearance from the circulation.…”

“…Several approaches have been used for PET and SPECT of HER2 expression, including radiolabeled antibodies trastuzumab and pertuzumab (HER2 dimerization inhibitor) and radiolabeled trastuzumab fragments (13)(14)(15)(16). These radiotracers were able to visualize HER2 expression, but their large size resulted in slow tumor accumulation and slow clearance from the circulation.…”

Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging

“…Using SPECT, we have shown HER2/neu-specific uptake of this radiopharmaceutical in xenograft-bearing animals (14) and HER2/neu-positive metastatic breast cancer patients (15). 111 In-diethylaminetriaminepentaacetic acid (DTPA)-trastuzumab scintigraphy revealed new tumor lesions in 13 of 15 patients and was therefore considered to be of potential value for clinical staging (15).…”

Targeting EGFR and HER2 for Molecular Imaging of Cancer

“…The SK-OV-3 tumor showed substantial uptake of the labeled antibody after 5 h. The difference in uptake between SK-OV-3 and GLC4 tumors was even more pronounced 3 d after injection. At that time, the SK-OV-3 tumor was clearly visualized by radioimmunoscintigraphy (Lub-de Hooge et al, 2004). Research has also demonstrated that fluorescent dye-labeled trastuzumab enabled differentiation between breast cancer cells expressing high and low levels of HER2.…”