Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron–Based Radionuclide Therapy

Journal of Nuclear Medicine

Poul Flemming Høilund-Carlsen¹  Johan Hygum Dam¹  Helge Thisgaard¹  Peter Bollen¹  Jan Mollenhauer¹  Birgitte Brinkmann Olsen¹ 

关键词: Auger electrons;    radionuclide therapy;    DOTATATE;    ^58mCo;    ¹⁷⁷Lu;   

DOI  :  10.2967/jnumed.114.137182

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The somatostatin receptor, which is overexpressed by many neuroendocrine tumors, is a well-known target for molecular imaging and peptide receptor radionuclide therapy. Recently, 57Co-labeled DOTATOC, an octreotide analog, was shown to have the highest affinity yet found for somatostatin receptor subtype 2. The aim of this study was to evaluate the biologic effects of novel cobalt-labeled octreotide analogs targeting the somatostatin receptor to identify promising candidates for molecular imaging and Auger electron–based radionuclide therapy. Methods: Cobalt-labeled DOTATATE, DOTATOC, and DOTANOC were prepared with 57Co or 58mCo for SPECT or Auger electron–based therapy, respectively. The cellular uptake and intracellular distribution of the radioligands were characterized with the pancreatic tumor cell line AR42J in vitro, including assessment of the therapeutic effects of 58mCo-DOTATATE via DNA double-strand break and proliferation assays. Comparisons with the therapeutic effects of 111In- and 177Lu-DOTATATE were also performed. Tumor uptake and normal tissue uptake were characterized in a subcutaneous pancreatic tumor mouse model. Results: All 3 cobalt-conjugated peptides resulted in time-dependent and receptor-specific uptake, with a high level (≥88%) of cellular internalization in vitro of the total cell-associated radioactivity. The DNA double-strand break yield showed a dose-dependent increase with activity, whereas cell survival showed a dose-dependent decrease. 58mCo-DOTATATE was significantly more efficient in cell killing per cumulated decay than 111In- and 177Lu-DOTATATE. The in vivo pharmacokinetic studies showed a high level of receptor-specific tumor uptake. Conclusion: All cobalt-labeled radioligands showed a high level of receptor-specific uptake both in vitro and in vivo in tumor-bearing mice. Furthermore, 58mCo-DOTATATE showed considerable therapeutic effects in vitro and, thus, could be an effective agent for eradicating disseminated tumor cells and micrometastases.

【 授权许可】

Unknown