Purpose: The new antibody pertuzumab (Omnitarg) targets the dimerisation subdomain of HER-2. The purpose of this study was to analyse whether pertuzumab retains HER-2 targeting capacity after labelling with the therapeutically interesting beta emitter 177Lu and to make initial characterisations in vitro and in vivo. Methods: Pertuzumab was conjugated with isothiocyanate-benzyl-CHX-A″-DTPA and chelated to 177Lu. Immunoreactivity, affinity, cellular retention and internalisation were analysed using SKOV-3 cells. The affinity of non-radioactive pertuzumab was measured using a surface plasmon resonance biosensor. In vivo targeting and specific binding were assessed in Balb/c (nu/nu) mice carrying SKOV-3 xenografts. The biodistribution of 177Lu was determined 1, 3 and 7 days after [ 177Lu]pertuzumab administration. Gamma camera images were taken after 3 days. Results: The immunoreactivity of [177Lu]pertuzumab was 85.8±1.3%. The affinity of non-radioactive pertuzumab was 1.8±1.1 nM, and that of [177Lu]pertuzumab, 4.1± 0.7 nM. The cellular retention after 5 h pre-incubation was 90±2% at 20 h. The targeting was HER-2 specific both in vitro and in vivo, since excess amounts of non-labelled antibody inhibited the uptake of labelled antibody (p<.0001 and p<0.01, respectively). The biodistribution and gamma camera images of 177Lu showed extensive tumour uptake. Normal tissues had a surprisingly low uptake. Conclusion: Pertuzumab was efficiently labelled with 177Lu and showed good intracellular retention and HER-2 specific binding both in vitro and in vivo. The gamma camera images and the biodistribution study gave excellent tumour targeting results. Thus, [177Lu]pertuzumab is of interest for further studies aimed at radionuclide therapy.
|Журнал||European Journal of Nuclear Medicine and Molecular Imaging|
|Состояние||Опубликовано - дек 2005|
|Опубликовано для внешнего пользования||Да|
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging