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Find video protocols related to scientific articles indexed in Pubmed.
Application of single-vial ready-for-use formulation of (111)In- or (177)Lu-labelled somatostatin analogs.
Appl Radiat Isot
PUBLISHED: 06-14-2013
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For the sake of safety it would be desirable to store and transport the ready-for-use liquid formulation (diagnostics and therapeutics) of radiolabelled peptides. The use of ethanol, in combination with a mixture of gentisic- and ascorbic acid, has superior effects on stabilizing radiolabelled somatostatin analogs. As a consequence, (111)In- and (177)Lu-labelled somatostatin analogs can be stored and transported in a single-vial ready-for-use liquid formulation up to 7 days after radiolabelling.
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Reversed phase free ion selective radiotracer extraction (RP-FISRE): A new tool to assess the dynamic stabilities of metal (-organic) complexes, for complex half-lives spanning six orders of magnitude.
Appl Radiat Isot
PUBLISHED: 05-20-2013
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This paper introduces reversed phase free ion selective radiotracer extraction (RP-FISRE) as a new tool to assess the stability of metal complexes, as illustrated by the assessment of the stability of [(177)Lu]Lu-DOTA-octreotate. To this end, the TUDelft-developed FISRE, where the released metal is column-retained and the complex eluted, was changed into RP-FISRE, where the complex is column-retained and the released metal is eluted. This change in the approach allows for studies to be performed with high stability complexes. This paper presents RP-FISRE, the strength of the radiotracer approach, and the first-ever kd data on the release of (177)Lu from [(177)Lu]Lu-DOTA-octreotate.
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Scaled-up radiolabelling of DOTATATE with 68Ga eluted from a SnO2-based 68Ge/68Ga generator.
Appl Radiat Isot
PUBLISHED: 07-11-2011
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A scaled-up radiolabelling and improved post-labelling purification procedure for [(68)Ga]DOTATATE is reported, using a more than 1 year old SnO(2)-based 1850MBq (68)Ge/(68)Ga generator (initially double-loaded with 3700MBq (68)Ge) as a source of ionic (68)Ga. The elution method of choice comprised elution with 0.6M HCl in a single 4mL fraction, containing up to 95% of the total eluted (68)Ga activity. The unpurified fraction was directly used for labelling after pH adjustment with 2.5M sodium acetate. Labelling efficiencies were determined at 90-95°C at various reaction times and reaction volumes of up to 5.7mL, using either 30?g or 50?g DOTATATE. Only the latter amount resulted in consistently high labelling efficiency in excess of 95%. Post-labelling purification, carried out on Sep-Pak C18, showed that 50% ethanol in saline was a superior desorption eluant than 100% ethanol. The highest and most consistent decay-corrected radiochemical yields (89%) were obtained using 50?g DOTATATE and a 20min reaction time.
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(68)Ga-labeled DOTA-peptides and (68)Ga-labeled radiopharmaceuticals for positron emission tomography: current status of research, clinical applications, and future perspectives.
Semin Nucl Med
PUBLISHED: 06-01-2011
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In this review we give an overview of current knowledge of (68)Ga-labeled pharmaceuticals, with focus on imaging receptor-mediated processes. A major advantage of a (68)Ge/(68)Ga generator is its continuous source of (68)Ga, independently from an on-site cyclotron. The increase in knowledge of purification and concentration of the eluate and the complex ligand chemistry has led to (68)Ga-labeled pharmaceuticals with major clinical impact. (68)Ga-labeled pharmaceuticals have the potential to cover all todays clinical options with (99m)Tc, with the concordant higher resolution of positron emission tomography (PET) in comparison with single photon emission computed tomography. (68)Ga-labeled analogs of octreotide, such as DOTATOC, DOTANOC, and DOTA-TATE, are in clinical application in nuclear medicine, and these analogs are now the most frequently applied of all (68)Ga-labeled pharmaceuticals. All the above-mentioned items in favor of successful application of (68)Ga-labeled radiopharmaceuticals for imaging in patients are strong arguments for the development of a (68)Ge/(68)Ga generator with Marketing Authorization and thus to provide pharmaceutical grade eluate. Moreover, now not one United States Food and Drug Administration-approved or European Medicines Agency-approved (68)Ga-radiopharmaceutical is available. As soon as these are achieved, a whole new radiopharmacy providing PET radiopharmaceuticals might develop.
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Comparison of the binding and internalization properties of 12 DOTA-coupled and ¹¹¹In-labelled CCK2/gastrin receptor binding peptides: a collaborative project under COST Action BM0607.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 04-04-2011
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Specific overexpression of cholecystokinin 2 (CCK2)/gastrin receptors has been demonstrated in several tumours of neuroendocrine origin. In some of these cancer types, such as medullary thyroid cancer (MTC), a sensitive diagnostic modality is still unavailable and therapeutic options for inoperable lesions are needed. Peptide receptor radionuclide therapy (PRRT) may be a viable therapeutic strategy in the management of these patients. Several CCK2R-targeted radiopharmaceuticals have been described in recent years. As part of the European Union COST Action BM0607 we studied the in vitro and in vivo characteristics of 12 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated CCK2R binding peptides. In the present study, we analysed binding and internalization characteristics. Stability, biodistribution and imaging studies have been performed in parallel by other centres involved in the project.
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Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides.
Appl Radiat Isot
PUBLISHED: 08-07-2010
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PET scintigraphy with (68)Ga-labelled analogs is of increasing interest in Nuclear Medicine and performed all over the world. Here we report the characteristics of the eluate of SnO(2)-based (68)Ge/(68)Ga generators prepared by iThemba LABS (Somerset West, South Africa). Three purification and concentration techniques of the eluate for labelling DOTA-TATE and concordant SPE purifications were investigated.
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Effectiveness of quenchers to reduce radiolysis of (111)In- or (177)Lu-labelled methionine-containing regulatory peptides. Maintaining radiochemical purity as measured by HPLC.
Curr Top Med Chem
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An overview how to measure and to quantify radiolysis by the addition of quenchers and to maintain Radio-Chemical Purity (RCP) of vulnerable methionine-containing regulatory peptides is presented. High RCP was only achieved with a combination of quenchers. However, quantification of RCP is not standardized, and therefore comparison of radiolabelling and RCP of regulatory peptides between different HPLC-systems and between laboratories is cumbersome. Therefore we suggest a set of standardized requirements to quantify RCP by HPLC for radiolabelled DTPA- or DOTA-peptides. Moreover, a dosimetry model was developed to calculate the doses in the reaction vials during radiolabelling and storage of the radiopeptides, and to predict RCP in the presence and absence of quenchers. RCP was measured by HPLC, and a relation between radiation dose and radiolysis of RCP was established. The here described quenchers are tested individually as ƒ(concentration) to investigate efficacy to reduce radiolysis of radiolabelled methionine-containing regulatory peptides.
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Iodination and stability of somatostatin analogues: comparison of iodination techniques. A practical overview.
Curr Top Med Chem
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For iodination ((125/127)I) of tyrosine-containing peptides, chloramin-T, Pre-Coated Iodo-Gen(®) tubes and Iodo-Beads(®) (Pierce) are commonly used for in vitro radioligand investigations and there have been reliant vendors hereof for decades. However, commercial availability of these radio-iodinated peptides is decreasing. For continuation of our research in this field we investigated and optimized (radio-)iodination of somatostatin analogues. In literature, radioiodination using here described somatostatin analogues and iodination techniques are described separately. Here we present an overview, including High Performance Liquid Chromatography (HPLC) separation and characterisation by mass spectrometry, to obtain mono- and di-iodinated analogues. Reaction kinetics of (125/127)I iodinated somatostatin analogues were investigated as function of reaction time and concentration of reactants, including somatostatin analogues, iodine and oxidizing agent. To our knowledge, for the here described somatostatin analogues, no (127)I iodination and optimization are described. (Radio-)iodinated somatostatin analogues could be preserved with a >90% radiochemical purity for 1 month after reversed phase HPLC-purification.
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The untapped potential of Gallium 68-PET: the next wave of ??Ga-agents.
Appl Radiat Isot
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(68)Gallium-PET ((68)Ga-PET) agents have significant clinical promise. The radionuclide can be produced from a (68)Ge/(68)Ga generator on site and is a convenient alternative to cyclotron-based PET isotopes. The short half-life of (68)Ga permits imaging applications with sufficient radioactivity while maintaining patient dose to an acceptable level. Furthermore, due to superior resolution, (68)Ga-PET agents have the ability to replace current SPECT agents in many applications. This article outlines the upcoming agents and challenges faced during the translational development of (68)Ga agents.
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A new automated NaCl based robust method for routine production of gallium-68 labeled peptides.
Appl Radiat Isot
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A new NaCl based method for preparation of gallium-68 labeled radiopharmaceuticals has been adapted for use with an automated gallium-68 generator system. The method was evaluated based on 56 preparations of [(68)Ga]DOTATOC and compared to a similar acetone-based approach. Advantages of the new NaCl approach include reduced preparation time (<15 min) and removal of organic solvents. The method produces high peptide-bound % (>97%), and specific activity (>40 MBq nmole(-1) [(68)Ga]DOTATOC) and is well-suited for clinical production of radiopharmaceuticals.
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Simplified NaCl based (68)Ga concentration and labeling procedure for rapid synthesis of (68)Ga radiopharmaceuticals in high radiochemical purity.
Bioconjug. Chem.
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A simple sodium chloride (NaCl) based (68)Ga eluate concentration and labeling method that enables rapid, high-efficiency labeling of DOTA conjugated peptides in high radiochemical purity is described. The method utilizes relatively few reagents and comprises minimal procedural steps. It is particularly well-suited for routine automated synthesis of clinical radiopharmaceuticals. For the (68)Ga generator eluate concentration step, commercially available cation-exchange cartridges and (68)Ga generators were used. The (68)Ga generator eluate was collected by use of a strong cation exchange cartridge. 98% of the total activity of (68)Ga was then eluted from the cation exchange cartridge with 0.5 mL of 5 M NaCl solution containing a small amount of 5.5 M HCl. After buffering with ammonium acetate, the eluate was used directly for radiolabeling of DOTATOC and DOTATATE. The (68)Ga-labeled peptides were obtained in higher radiochemical purity compared to other commonly used procedures, with radiochemical yields greater than 80%. The presence of (68)Ge could not be detected in the final product. The new method obviates the need for organic solvents, which eliminates the required quality control of the final product by gas chromatography, thereby reducing postsynthesis analytical effort significantly. The (68)Ga-labeled products were used directly, with no subsequent purification steps, such as solid-phase extraction. The NaCl method was further evaluated using an automated fluid handling system and it routinely facilitates radiochemical yields in excess of 65% in less than 15 min, with radiochemical purity consistently greater than 99% for the preparation of (68)Ga-DOTATOC.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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