Abstract | UNLABELLED: METHODS:
Cobalt-labeled DOTATATE, DOTATOC, and DOTANOC were prepared with (57)Co or (58m)Co 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 (58m)Co-DOTATATE via DNA double-strand break and proliferation assays. Comparisons with the therapeutic effects of (111)In- and (177)Lu-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. (58m)Co-DOTATATE was significantly more efficient in cell killing per cumulated decay than (111)In- and (177)Lu-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, (58m)Co-DOTATATE showed considerable therapeutic effects in vitro and, thus, could be an effective agent for eradicating disseminated tumor cells and micrometastases.
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Authors | Helge Thisgaard, Birgitte Brinkmann Olsen, Johan Hygum Dam, Peter Bollen, Jan Mollenhauer, Poul Flemming Høilund-Carlsen |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 55
Issue 8
Pg. 1311-6
(Aug 2014)
ISSN: 1535-5667 [Electronic] United States |
PMID | 24876207
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc. |
Chemical References |
- Cobalt Radioisotopes
- Octreotide
|
Topics |
- Animals
- Cell Line, Tumor
- Cell Proliferation
(radiation effects)
- Cobalt Radioisotopes
(therapeutic use)
- DNA Breaks, Double-Stranded
(radiation effects)
- Electrons
- Female
- Mice
- Molecular Imaging
(methods)
- Octreotide
(analogs & derivatives, therapeutic use)
- Pancreatic Neoplasms
(diagnostic imaging, pathology, radiotherapy)
- Radiotherapy
(methods)
- Rats
- Tomography, Emission-Computed, Single-Photon
- Tomography, X-Ray Computed
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