[177Lu]pertuzumab: experimental studies on targeting of HER-2 positive tumour cells

PurposeThe 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.MethodsPertuzumab 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.ResultsThe 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<0.0001 and p<0.01, respectively). The biodistribution and gamma camera images of 177Lu showed extensive tumour uptake. Normal tissues had a surprisingly low uptake.ConclusionPertuzumab 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.