Abstract
BackgroundTerbium 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 α- and β−-radionuclide therapy. The aim of this study was to produce 152Tb (T1/2 = 17.5 h, Eβ+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.Methods152Tb was produced by proton-induced spallation of tantalum targets, followed by an online isotope separation process at ISOLDE/CERN. After separation of 152Tb 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 152Tb-DOTANOC which was applied at variable molar peptide amounts. 177Lu-DOTANOC was prepared and used in biodistribution and SPECT/CT imaging studies for comparison with the PET results.ResultsAfter purification, 152Tb was obtained at activities up 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 152Tb-DOTANOC at small peptide amounts, revealed the best tumor-to-kidney ratios. The data obtained with 177Lu-DOTANOC in biodistribution and SPECT/CT imaging studies confirmed the 152Tb-based PET results.ConclusionsProduction of 30-fold higher quantities of 152Tb 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 β+-particle-emitting radiolanthanide, 152Tb would be of distinct value for clinical application, as it may allow exact prediction of the tissue distribution of therapeutic radiolanthanides.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0189-4) contains supplementary material, which is available to authorized users.
Highlights
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 α- and β−-radionuclide therapy
Other longer-lived PET nuclides such as 89Zr (T1/2 = 3.26 days) and 64Cu (T1/2 = 12.7 h) exist, these nuclides have different chemical properties and, different chelators are necessary for stable coordination [18,19,20]. 68Ga is currently successfully used for PET imaging prior to 177Lu-based radionuclide therapy [11, 21], its short half-life and different coordination chemistry, which may result in different pharmacokinetics [22], would clearly speak in the favor of using a matched radiolanthanide for PET and, justify the development and investigation of 152Tb
Based on the resulting data, 152Tb is a promising candidate to be used as diagnostic match to therapeutic radiolanthanides, potentially allowing exact pre-therapeutic imaging and dosimetry calculations
Summary
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 α- and β−-radionuclide therapy. The aim of this study was to produce 152Tb (T1/2 = 17.5 h, Eβ+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. Terbium has attracted the attention of researchers in radiopharmaceutical sciences due to the existence of four medically interesting radionuclides for SPECT (155Tb) and PET (152Tb) imaging, as well as for α- (149Tb) and β−-radionuclide (161Tb) therapy. Based on the results of these studies, it is likely that the co-emitted Auger and conversion electrons of 161Tb contributed positively to the overall anti-tumor effects, while additional side effects to the kidneys were not observed [6]
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