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[¹⁷⁷Lu]Pertuzumab: Experimental Therapy of HER-2–Expressing Xenografts

Departments of ¹ Biomedical Radiation Sciences, ² Experimental Urology, and ³ Molecular and Morphological Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

Requests for reprints: Mikael Persson, Department of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, SE-75185, Uppsala, Sweden. Phone: 46-18-4713829; Fax: 46-18-4713432; E-mail: mikael.persson{at}bms.uu.se or Jörgen Carlsson. Phone: 46-18-4713841; Fax: 46-18-4713432; E-mail: jorgen.carlsson{at}bms.uu.se.

Pertuzumab (Omnitarg) is a novel antibody against HER-2, domain II. HER-2 is a tyrosine kinase receptor that is overexpressed in several carcinomas, especially breast cancer. Pertuzumab, labeled with the low-energy ß emitter ¹⁷⁷Lu, might be a candidate for targeted radiotherapy of disseminated HER-2–positive micrometastases. The radiolabeled antibody [¹⁷⁷Lu]pertuzumab showed favorable targeting properties in BALB/c (nu/nu) mice with HER-2–overexpressing xenografts. The absorbed dose in tumors was more than five times higher than the absorbed dose in blood and more than seven times the absorbed dose in any other normal organ. Experimental therapy showed that [¹⁷⁷Lu]pertuzumab delayed tumor progression compared with controls (no treatment, P < 0.0001; nonlabeled pertuzumab antibody, P < 0.0001; and ¹⁷⁷Lu-labeled irrelevant antibody, P < 0.01). No adverse side effects of the treatment could be detected. Thus, the experimental results support the planning of clinical studies applying [¹⁷⁷Lu]pertuzumab for therapy. [Cancer Res 2007;67(1):326–31]

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				V. Tolmachev, A. Orlova, R. Pehrson, J. Galli, B. Baastrup, K. Andersson, M. Sandstrom, D. Rosik, J. Carlsson, H. Lundqvist, et al. Radionuclide Therapy of HER2-Positive Microxenografts Using a 177Lu-Labeled HER2-Specific Affibody Molecule Cancer Res., March 15, 2007; 67(6): 2773 - 2782. [Abstract] [Full Text] [PDF]