期刊
EJNMMI RESEARCH
卷 6, 期 -, 页码 -出版社
SPRINGEROPEN
DOI: 10.1186/s13550-016-0189-4
关键词
Tb-152; PET; DOTANOC; Tumor imaging; AR42J tumors; ISOLDE
Background: Terbium has attracted the attention of researchers and physicians due to the existence of four medically interesting radionuclides, potentially useful for SPECT and PET imaging, as well as for alpha(-) and beta(-) -radionuclide therapy. The aim of this study was to produce Tb-152 ( T-1/2 = 17.5 h, E beta+av = 1140 keV) and evaluate it in a preclinical setting in order to demonstrate its potential for PET imaging. For this purpose, DOTANOC was used for targeting the somatostatin receptor in AR42J tumor-bearing mice. Methods: Tb-152 was produced by proton-induced spallation of tantalum targets, followed by an online isotope separation process at ISOLDE/CERN. After separation of Tb-152 using cation exchange chromatography, it was directly employed for radiolabeling of DOTANOC. PET/CT scans were performed with AR42J tumor-bearing mice at different time points after injection of Tb-152-DOTANOC which was applied at variable molar peptide amounts. Lu-177-DOTANOC was prepared and used in biodistribution and SPECT/CT imaging studies for comparison with the PET results. Results: After purification, Tb-152 was obtained at activities up to similar to 600 MBq. Radiolabeling of DOTANOC was achieved at a specific activity of 10 MBq/nmol with a radiochemical purity >98 %. The PET/CT scans of mice allowed visualization of AR42J tumor xenografts and the kidneys, in which the radiopeptide was accumulated. After injection of large peptide amounts, the tumor uptake was reduced as compared to the result after injection of small peptide amounts. PET images of mice, which received Tb-152-DOTANOC at small peptide amounts, revealed the best tumor-to-kidney ratios. The data obtained with Lu-177-DOTANOC in biodistribution and SPECT/CT imaging studies confirmed the Tb-152-based PET results. Conclusions: Production of 30-fold higher quantities of Tb-152 as compared to the previously performed pilot study was feasible. This allowed, for the first time, labeling of a peptide at a reasonable specific activity and subsequent application for in vivo PET imaging. As a beta(+)-particle-emitting radiolanthanide, Tb-152 would be of distinct value for clinical application, as it may allow exact prediction of the tissue distribution of therapeutic radiolanthanides.
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