Enhancement of reaction conditions for the radiolabelling of DOTA-peptides with high activities of yttrium-90 (original) (raw)
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International Journal of Diagnostic Imaging, 2014
Purpose: Radiolabeled peptides like 177Lu-DOTA-TATE are vulnerable to radiolysis, which results in decreasedradiochemical purity (RCP) of these radiopeptides. Gentisic acid (GA) and ascorbic acid (AA) are well known ingredientsto reduce the effects of radiolysis. Currently, there is a trend to change the procedure from a manual to a cassette-basedautomated labeling and to introduce a C18 solid phase extraction (SPE) post-radiolabeling in order to removenon-incorporated 177Lu from the injection solution. However, with the introduction of SPE purification, GA and AAmight effectively be removed from injection solution with a concordant dramatically drop of the RCP. Therefore weinvestigated the impact of tC18 SPE purification on the RCP of 177Lu-DOTA-TATE.Methods: We compared the manual radiolabeling procedure with the cassette-based automated radiolabeling procedurewith/out tC18 SPE purification cartridge. The effect of tC18 purification on RCP of 177Lu-DOTA-TATE wasinvestigated by HPL...
Gallium-68 (68 Ga) is a generator-produced radionuclide with a short half-life (t ½ = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize 68 Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging. By working in a lead-shielded hot-cell system, 68 Ga 3+ of the generator eluate is trapped on a cation exchanger cartridge (100 mg, ∼8 mm long and 5 mm diameter) and then eluted with acidified 5 M NaCl solution directly into a sodium acetate-buffered solution containing a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or DOTA-like chelator-modified peptide. The main advantages of this procedure are the high efficiency and the absence of organic solvents. It can be applied to a variety of peptides, which are stable in 1 M NaCl solution at a pH value of 3-4 during reaction. After labeling, neutralization, sterile filtration and quality control (instant thin-layer chromatography (iTLC), HPLC and pH), the radiopharmaceutical can be directly administered to patients, without determination of organic solvents, which reduces the overall synthesis-to-release time. This procedure has been adapted Reprints and permissions information is available online at http://www.nature.com/reprints/index.html. Correspondence should be addressed to D.M.
Nuclear Medicine Communications, 2012
Objectives The treatment of tumours expressing somatostatin receptors with yttrium-90 ( 90 Y)-labelled and lutetium-177 ( 177 Lu)-labelled somatostatin analogues is one of the most interesting therapeutic approaches adopted in nuclear medicine in recent years. However, the process of synthesis and fractionation of these radiopharmaceuticals is still mainly carried out manually despite the high radiation exposure to the operators and the need to comply with good manufacturing practices. In this study a semiautomatic synthesizer [automatic dose dispenser (ADD-2)] using only disposable syringes and vials has been presented.
Synthesis of radioiodinated labeled peptides
Journal of Radioanalytical and Nuclear Chemistry, 2003
This report covers optimization of radioiodination of peptides by both a direct method in which a constituent tyrosine residue is labeled and indirect method by using an iodinated derivative (SIB) of N succinimidyl 3-(tri-n-butylstannyl) benzoate (ATE) as the intermediate. Radioiodination of IgG and FMLF were performed by direct method using Chloramine-T as an oxidant but since Formyl-Methyl-Leucyl-Phenylalanine, FMLF, does not lend itself for direct radioiodination we performed labeling of FMLF by indirect method via radioiodined SIB at different pH.
2017
Background 213Bismuth (213Bi, T1/2 = 45.6 min) is one of the most frequently used α-emitters in cancer research. High specific activity radioligands are required for peptide receptor radionuclide therapy. The use of generators containing less than 222 MBq 225Ac (actinium), due to limited availability and the high cost to produce large-scale 225Ac/213Bi generators, might complicate in vitro and in vivo applications though. Here we present optimized labelling conditions of a DOTA-peptide with an 225Ac/213Bi generator (< 222 MBq) for preclinical applications using DOTA-Tyr3-octreotate (DOTATATE), a somatostatin analogue. The following labelling conditions of DOTATATE with 213Bi were investigated; peptide mass was varied from 1.7 to 7.0 nmol, concentration of TRIS buffer from 0.15 mol.L-1 to 0.34 mol.L-1, and ascorbic acid from 0 to 71 mmol.L-1 in 800 μL. All reactions were performed at 95 °C for 5 min. After incubation, DTPA (50 nmol) was added to stop the labelling reaction. Beside...
Standard test of labelling for efficiency for quality control of no carrier added 90YCL3
Nucleus, 2007
Particle emitting radionuclides (e.g. β-emitters 90 Y and 177 Lu, β-emitter 149 Tb, Auger electron emitter 165 Er or positron emitter 86 Y) are more and more frequently used in research and clinical practice for imaging and radionuclide targeted therapy in nuclear medicine. These radiometals, altogether threevalent lanthanides or actinides with high specific radioactivity, coupled to biomolecule carriers (peptides or monoclonal antibodies) through chelating link (e.g. DTPA or DOTA) bind to specific antigens and/or receptors of diseased tissues, which enables the imaging (positron emitters) or destruction (β-, α-, and Auger electron emitter) of the diseased tissue releasing the antigens or carrying the receptors. The radionuclide precursor 90 YCl 3 (solution of hard β-emitter 90 Y in diluted HCl) with high purity and specific activity is already commercially produced and succesfully used in nuclear medicine, e.g. for radioimmunotherapy (RIT) of Lymphoma. Specification and purity of our product obtained using extraction 90 Sr/ 90 Y generator (using technology of centrifuge extractors with di-2ethylhexylphosphoric acid, D2EHPA) is examined and compared to other similar products in this contribution. A standard method for determination of labelling efficiency of the 90 YCl 3 precursor based on its reaction with DOTA-Tyr 3-Octreotide (DOTA-TOC) and ITLC-SG chromatographic separation is described and proposed for the quality control. PRUEBA ESTÁNDAR DE LA EFICIENCIA DEL MARCAJE PARA EL CONTROL DE LA CALIDAD DEL 90 YCI 3 SIN PORTADOR AÑADIDO Resumen Los radionucleidos emisores de partículas (ej. emisores β 90 Y y 177 Lu, emisores α 149 Tb, emisor de electrones Auger 165 Er o emisor de positrones 86 Y) se emplean cada vez más en la investigación, en la práctica clínica para el procesamiento de imágenes y en la terapia dirigida de radionuclidos en medicina nuclear. Estos radiometales junto con actínidos o lantánidos trivalentes con alta actividad específica, asociados a portadores de biomoléculas (péptidos o anticuerpos monoclonales) por medio de un enlace con quelatos (ej. DTPA o DOTA) se unen a antígenos específicos receptores de tejidos afectados que permiten el procesamiento de imágenes (emisores de positrones) o la destrucción (β-, α-, y emisores de electrones de Auger) de los tejidos afectados que liberan los antígenos o portan los receptores. El precursor del radionucleido 90 YCI 3 (solución de emisor βduro-90 Y en HCI diluido) con elevada pureza y actividad específica ya se produce comercialmente y se usa exitosamente en la medicina nuclear, por ejemplo, para la radioinmunoterapia (RIT) del linfoma. En esta contribución se examina la especificación y la pureza de nuestro producto, obtenido mediante extracción con generador 90 Sr/ 90 Y (empleando la tecnología de extractores por centrifugado con ácido di-2-ethylhexyl phosphoric D2EHPA) y se compara con otros productos similares. Se describe y propone para el control de la calidad un método estándar para determinar la eficiencia en el marcaje del precursor del 90 YCI 3 basado en su reacción con DOTA-Tyr 3-ostreotido (DOTA-TOC) y separación cromatográfica ITLC-SG.
Nuclear Medicine Communications, 2011
Objectives Radiolabelled somatostatin analogues have found wide clinical use in nuclear medicine for both diagnostic and therapeutic applications. Here, we describe the development of a fully automated synthesis system allowing radiolabelling of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-derivatized peptides with 68 Ga/ 111 In/ 177 Lu and 90 Y, meeting radiation safety and pharmaceutical requirements.
Applied Radiation and Isotopes, 2008
Somatostatin receptors 1-5 are over expressed in neuroendocrine tumours (NETs). 68 4,7,4,7,10-tetraacetic acid]-1-Nal3-Octreotide (DOTA NOC), a recent synthesized somatostatin analogue, shows high affinity for those receptors. Herein, modifications of a commercial module for the labelling of DOTA NOC with 68 Ga, as well as the assessment of time course of the radiochemical purity variation are described. The evaluation of radiochemical stability was done by two different chromatographic methods: reversed-phase radio HPLC and fast TLC analysis. Labelled compound has been found radiochemically stable within 3 h from the end of labelling (EOL) and radiochemical purity was always higher than 99%. After 73 labelling sessions the system showed great reproducibility and high radiochemical yield. r
Contrast Media & Molecular Imaging, 2017
In spite of the hazard due to the radiation exposure, preparation of 90Y- and 177Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of 177Lu- and 90Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617) was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both 90Y- and 177Lu-labelled radiopharmaceuticals have been performed using the three different methods. The mean radiochemical yields for 90Y-DOTATOC were 96.2±4.9%, 90.3±5.6%, and 82.0±8.4%, while for 177Lu-DOTATOC they were 98.3% ± 0.6, 90.8% ± 8.3, and 83.1±5.7% when manual, semiautomated, and automated approaches were used, respectively. The mean doses on the whole hands for yttrium-90 preparations were 0.15±0.4 mSv/GBq, 0.04±0.1 mSv/GBq, and 0.11±0.3 mS...