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

Eur J Nucl Med Mol Imaging. 2005 Dec;32(12):1457-62. doi: 10.1007/s00259-005-1902-0. Epub 2005 Sep 29.


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 (177)Lu and to make initial characterizations in vitro and in vivo.

Methods: Pertuzumab was conjugated with isothiocyanate-benzyl-CHX-A''-DTPA and chelated to (177)Lu. 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 (177)Lu was determined 1, 3 and 7 days after [(177)Lu]pertuzumab administration. Gamma camera images were taken after 3 days.

Results: The immunoreactivity of [(177)Lu]pertuzumab was 85.8+/-1.3%. The affinity of non-radioactive pertuzumab was 1.8+/-1.1 nM, and that of [(177)Lu]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 (177)Lu showed extensive tumour uptake. Normal tissues had a surprisingly low uptake.

Conclusion: Pertuzumab was efficiently labelled with (177)Lu 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, [(177)Lu]pertuzumab is of interest for further studies aimed at radionuclide therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Cell Line, Tumor
  • Drug Delivery Systems / methods
  • Female
  • Humans
  • Lutetium / chemistry
  • Lutetium / pharmacokinetics*
  • Lutetium / therapeutic use
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Organ Specificity
  • Ovarian Neoplasms / diagnostic imaging
  • Ovarian Neoplasms / metabolism*
  • Radioimmunotherapy / methods
  • Radioisotopes / chemistry
  • Radioisotopes / pharmacokinetics*
  • Radioisotopes / therapeutic use
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Receptor, ErbB-2 / metabolism*
  • Staining and Labeling
  • Tissue Distribution


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Radioisotopes
  • Radiopharmaceuticals
  • Lutetium
  • Receptor, ErbB-2
  • pertuzumab