Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice

Müller, Cristina; Fischer, Eliane; Béhé, Martin; Köster, U.; Dorrer, Holger; Reber, Josefine; Haller, Stephanie; Cohrs, Susan; Blanc, Alain; Grünberg, Jürgen; Bunka, Maruta; Zhernosekov, Konstantin; Meulen, Nicholas P. van der; Johnston, K.; Türler, Α.; Schibli, Roger

doi:10.1016/j.nucmedbio.2013.11.002

Cited by 62 publications

(43 citation statements)

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“…Two other Tb nuclides, 155 Tb and 152 Tb, are suited for diagnostic applications. Recently, preclinical experiments were performed in order to investigate 155 Tb in more detail with regard to its potential for SPECT imaging [ 10 ]. For this purpose, several DOTA-functionalized tumor targeting agents, among those also peptides and an antibody, were employed for imaging of tumors in mice [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, preclinical experiments were performed in order to investigate 155 Tb in more detail with regard to its potential for SPECT imaging [ 10 ]. For this purpose, several DOTA-functionalized tumor targeting agents, among those also peptides and an antibody, were employed for imaging of tumors in mice [ 10 ]. The image quality of the 155 Tb-based SPECT scans was convincing and allowed not only the visualization of subcutaneous tumor xenografts, but also smallest lesions in the abdominal tract of a mouse with intraperitoneal SKOV-3ip xenografts [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…For this purpose, several DOTA-functionalized tumor targeting agents, among those also peptides and an antibody, were employed for imaging of tumors in mice [ 10 ]. The image quality of the 155 Tb-based SPECT scans was convincing and allowed not only the visualization of subcutaneous tumor xenografts, but also smallest lesions in the abdominal tract of a mouse with intraperitoneal SKOV-3ip xenografts [ 10 ]. 155 Tb-based SPECT imaging was also investigated using a Derenzo phantom, which proved that the achievable image resolution was comparable to the resolution of 111 In, a clinically well-established SPECT nuclide [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Preclinical in vivo application of 152Tb-DOTANOC: a radiolanthanide for PET imaging

et al. 2016

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preclinical in vivo application of 152Tb-DOTANOC: a radiolanthanide for PET imaging

et al. 2016

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“…Affinity tests are now necessary to assess its potential utility. DOTATATE has also been labeled with 155 Tb (T 1/2 = 5.32 days, E γ = 87 keV (32%), 105 keV (25%)) for SPECT imaging [ 137 ]. Though a potentially promising radionuclide for theranostic applications, availability of 155 Tb is currently the main limitation for further development.…”

Section: Targeting Of Somatostatin Receptors With Radiopharmaceutimentioning

confidence: 99%

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

et al. 2020

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Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand–receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.

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“…Terbium (Tb) is the only element in Mendeleev's periodic table, which possesses four complementary medically relevant radioisotopes that appear to be well suited for the theranostics approach [4]. Specifically, 149 Tb is a promising radionuclide for α-therapy [5,6]; 152 Tb and 155 Tb can be used for PET and SPECT imaging, respectively [7,8]; and 161 Tb is appropriate for β − -therapy [9]. With the exception of 161 Tb (which can be produced via the 160 Gd(n,γ ) 161 Gd → 161 Tb reaction at a nuclear reactor), the aforementioned isotopes can be generated through spallation process Ta(p,x)Tb or irradiating a gadolinium (Gd) target at an accelerator [10].…”

Section: Introductionmentioning

confidence: 99%

First laser ions at the CERN-MEDICIS facility

et al. 2020

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The CERN-MEDICIS facility aims to produce emerging medical radionuclides for the theranostics approach in nuclear medicine with mass separation of ion beams. To enhance the radioisotope yield and purity of collected samples, the resonance ionization laser ion source MELISSA was constructed, and provided the first laser ions at the facility in 2019. Several operational tests were accomplished to investigate its performance in preparation for the upcoming production of terbium radioisotopes, which are of particular interest for medical applications.

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Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice

Cited by 62 publications

References 30 publications

Preclinical in vivo application of 152Tb-DOTANOC: a radiolanthanide for PET imaging

Preclinical in vivo application of 152Tb-DOTANOC: a radiolanthanide for PET imaging

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

First laser ions at the CERN-MEDICIS facility

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