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

Mikael Persson, Vladimir Tolmachev, Karl Andersson, Lars Gedda, Mattias Sandström, Jörgen Carlsson

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1457-1462
Number of pages6
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume32
Issue number12
DOIs
Publication statusPublished - Dec 2005
Externally publishedYes

Keywords

  • HER-2
  • Imaging
  • Radionuclide
  • Therapy
  • Tumour

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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