RESUMEN
Europium-154 can be obtained as a by-product from the large-scale production of Samarium-153 and possesses attractive features (t1/2 8.592 yr; Egamma 0.12-1.6 MeV) for use as a reference source similar to 152Eu (t1/2 13.516 yr; Egamma 0.12-1.4 MeV), which is the gold standard for calibration in gamma ray spectrometry. Thermal neutron irradiation of 5mg of 98% enriched 153Sm2O3 target in the reactor led to approximately 200 GBq 153Sm and 1.26 MBq 154Eu. A typical batch control sample of 153SmCl3 solution and final radiopharmaceutical product formulation of 153Sm-phosphonate (153Sm-EDTMP) pooled together contained about 20% of total yield, requiring post decay disposal of 153Sm as radioactive waste. Such spent solutions pooled on quarterly basis led to availing 756 kBq of 154Eu. The radioactivity content and radionuclide purity (approximately 82%) of the recovered 154Eu sample were envisaged as adequate to prepare reference sources for calibration of gamma ray spectrometers. At present, one batch of 153Sm is handled per month at our institution, with the possibility for weekly processing in future. Access to approximately 3.5 MBq of 154Eu on quarterly basis is envisaged, apart from obviating the need for instituting steps to tackle disposal of the long-lived 154Eu in the spent solution. Up to 60-120 units of 20-100 kBq of 154Eu reference sources per year could thus be available by the proposed strategy.
Asunto(s)
Europio/análisis , Europio/normas , Radioisótopos/análisis , Radioisótopos/normas , Estándares de Referencia , Espectrometría gamma/métodos , Espectrometría gamma/normas , Calibración/normas , Europio/química , India , Marcaje Isotópico/métodos , Marcaje Isotópico/normas , Radioisótopos/química , Samario/análisis , Samario/química , Samario/normasRESUMEN
BACKGROUND: Newer applications of radiopharmaceuticals in nuclear medicine require pertechnetate of moderate to high radioactive concentration. Hence there is a need to develop simple procedures for the concentration of pertechnetate, and such a procedure is given in this paper. METHODS: Ten to 20 ml of sodium [Tc]pertechnetate eluted in de-ionized water from a zirconium [Mo]molybdate (ZrMo) gel column generator was passed through 2 g of an acidic alumina bed (35 x 8 mm) in order to remove the co-eluted traces of Mo and to retain the pertechnetate. The retained pertechnetate was then re-eluted, quantitatively, in 3 ml of normal saline, from the alumina column. RESULTS: About a 4-fold increase in radioactive concentration of Tc was obtained (cf. approximately 10-12 ml normal saline is required for the elution of Tc from the gel column). Generators containing up to 22.2 GBq (600 mCi) Mo in 6-7 g ZrMo gel column (35 x 13 mm) were prepared and a radioactive concentration of Tc up to 4 GBq x ml (110 mCi x ml) was obtained on the first day of use. The overall recovery of Tc was >90%, Mo breakthrough was 10 to 10% and the duration of concentration was 3-5 min. The chemical impurity in terms of Al, Mo and Zr was <10 ppm each. The same procedure for the concentration of pertechnetate was applied to generators with 12-15 g ZrMo gel beds to obtain a higher capacity Tc gel generator, with similar findings.
Asunto(s)
Óxido de Aluminio/química , Cromatografía/métodos , Marcaje Isotópico/métodos , Molibdeno/química , Tecnecio/química , Tecnecio/aislamiento & purificación , Hidrogeles/química , Concentración de Iones de Hidrógeno , Radiofármacos/síntesis química , Radiofármacos/aislamiento & purificaciónRESUMEN
Owing to its favourable decay characteristics 177Lu [T(1/2)=6.71 d, Ebeta(max)=497 keV] is an attractive radionuclide for various therapeutic applications. Production of 177Lu using [176Lu (n,gamma)177Lu] reaction by thermal neutron bombardment on natural as well as enriched lutetium oxide target is described. In all, approximately 4 TBq/g (108 Ci/g) of 177Lu was obtained using natural Lu target after 7 d irradiation at 3 x 10(13) n/cm2/s thermal neutron flux while it was approximately 110 TBq/g (3000 Ci/g) of 177Lu when 60.6% enriched 176Lu target was used. In both the cases, radionuclidic purity was approximately 100%, only insignificant quantity of 177mLu [T(1/2)=160.5 d, Ebeta(max)=200 keV] could be detected as the radionuclidic impurity. Production logistics using different routes of production is compared. Possible therapeutic applications of 177Lu are discussed and its merits highlighted by comparison with other therapeutic radionuclides.
Asunto(s)
Lutecio/química , Lutecio/uso terapéutico , Radioisótopos/química , Radioisótopos/uso terapéutico , Radioterapia/métodos , Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Semivida , Humanos , Lutecio/aislamiento & purificación , Ensayo de Materiales , Cuidados Paliativos , Radioisótopos/aislamiento & purificación , Radiometría , Radiofármacos/síntesis química , Radiofármacos/química , Radiofármacos/aislamiento & purificación , Radiofármacos/uso terapéutico , Radioterapia/instrumentaciónRESUMEN
The dimethyl ester of diethylene triamine penta-acetic acid (DMDTPA) (I) can be easily and efficiently labelled with 99mTc. This method can be readily adapted for kit formulations to produce a highly stable and very pure chelate, as shown by paper electrophoresis and reverse-phase high performance liquid chromatography experiments. In mice, this chelate was excreted unchanged in the urine, and the amount of renal excretion was much higher than that of 99mTc-DTPA and comparable with that of 99mTc-mercaptoacetyl triglycine (99mTc-MAG(3)) at two different time points. The renal excretion of co-injected 131I-ortho-iodohippurate (131I-OIH), however, was significantly greater than that of the 99mTc chelates. The renal clearance values of 99mTc-DMDTPA and 99mTc-MAG(3) were also similar and exceeded the corresponding value for 99mTc-DTPA, but were only half that of the 131I-OIH value in the rat. The renograms for 99mTc-DMDTPA and 99mTc-MAG(3) showed overall similarity in a dog model. The diethyl ester (III) and monoethyl ester (II) of DTPA, after labelling with 99mTc, produced the same chelate, as shown by analytical results and biological data, indicating that one of the ester groups in the DTPA diester is dealkylated during the chelation procedure. To confirm this, two more ligands, diethylene triamine 1,4,7,7-tetra-acetic acid (IV) and diethylene triamine 1,4,7-triacetic acid (V), were synthesized, resembling DTPA monoalkyl ester (II) and dialkyl ester (I, III), respectively, in the arrangement of the donor atoms. Ligand IV but not ligand V, on 99mTc chelation, can generate the specific pharmacophore for renal tubular transport that is also present in the ester chelates 99mTc-I, 99mTc-II and 99mTc-III, as shown by their decreased renal excretion in mice pretreated with a renal tubular transport inhibitor such as probenecid.
Asunto(s)
Radioisótopos de Yodo/farmacocinética , Ácido Yodohipúrico/farmacocinética , Riñón/diagnóstico por imagen , Riñón/metabolismo , Renografía por Radioisótopo/métodos , Tecnecio Tc 99m Mertiatida/farmacocinética , Pentetato de Tecnecio Tc 99m/farmacocinética , Animales , Perros , Marcaje Isotópico/métodos , Masculino , Tasa de Depuración Metabólica , Ratones , Ratones Endogámicos BALB C , Radiofármacos/síntesis química , Pentetato de Tecnecio Tc 99m/análogos & derivados , Pentetato de Tecnecio Tc 99m/síntesis químicaRESUMEN
99Mo of specific activity 7.4-14.8GBq (200-400mCi)/g was adsorbed on a 'jumbo' alumina column (40g, 90mm(H) x 20mm (dia.); 50g, 65mm(H) x 35mm(dia.). [99mTc]TcO4-, eluted with 50-70ml normal saline and applied to a tiny column of a strong anion exchanger, Dowex-1 x 8, 10-15 mg, 8-12 mm(H) x 1 mm(dia.). Pertechnetate was eluted from the Dowex-1 column with 5-6 ml of 0.2M Nal followed by washing with 1.5-1.8 ml water. Iodide was removed from this eluate by passage through a 1 g AgCl column (12 mm (H) x 8 mm (dia.)). The final product, pertechnetate, was recovered in 6.5-7.8 ml, while the NaCl content was close to that of normal saline. Each elution operation was complete in approximately 45 min. The mean practical yield was approximately 86% (n = 5). Closed cycle operation with sterile connecting tubes and multi-way stop-cocks was practised. The quality of the [99mTc]NaTcO4 thus obtained complies with the specifications applicable for radiopharmaceutical use. The major merit over other post-elution concentration methods is that the new procedure can function nearly independently of the volume of the primary eluate (in normal saline) from the alumina column generator (ACG). 99mTc generators containing as much as 80-100 g alumina for holding 14.8-18.5GBq (400-500 mCi) 99Mo (at the reference time) are feasible using approximately 15 mg Dowex-1 bed mass. A relatively user-friendly--cum--producer-friendly 99mTc generator system has been demonstrated making use of the inexpensive and easy to prepare (n,gamma)99Mo. The method is also applicable for the more costly 188W-188Re generator.
Asunto(s)
Radiofármacos/farmacocinética , Compuestos de Anilina , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico por imagen , Glicina , Iminoácidos/farmacocinética , Lomustina , Compuestos de Organotecnecio/farmacocinética , Cintigrafía , Ratas , Ratas Wistar , Distribución TisularRESUMEN
The preparation of 166Ho labeled hydroxy apatite (HA) particles for radiosynovectomy applications is described in this paper. 166Ho was prepared by the irradiation of Ho2O3 at a flux of 1.8 x 10(13) neutrons/cm2/s for about 7 days. The irradiation resulted in the production of approximately 17 GBq of 166Ho activity at the end of six hours post end of bombardment and the corresponding specific activity was approximately 3-4 GBq/mg of Ho. The irradiated target was dissolved in 0.1 N HCl solution. Radionuclidic purity was ascertained by high resolution gamma ray spectrometry. HA particles were synthesized and characterized by X-ray diffractometry. Labeling studies were carried out with and without citric acid as a transchelating agent. Radiochemical yield and purity of the 166Ho-HA particles were ascertained by paper chromatography and by paper electrophoresis techniques. Labeling yield of >98% could be achieved at pH 7, with 40 mg of HA particles and 8.6 microg of Ho. 166Ho-HA particles prepared were stable for 72 h. Bio-evaluation of the 166Ho -HA particles were carried out by injecting approximately 74 MBq dose in 200 microL (approximately 8 mg of 166Ho-HA particles) directly into the arthritis induced knee joints as well as into the healthy knee joints of white New Zealand rabbits. Images of the injected joints of the animals recorded using a gamma camera at regular intervals showed good retention. Blood samples were collected from the animals and activity assayed in a scintillation detector. Experiments were also carried out under identical conditions in normal rabbits. In both the cases, it was observed that there was no significant extra articular leakage of the injected activity over the study period of 96 h post injection.
Asunto(s)
Holmio/uso terapéutico , Hidroxiapatitas/uso terapéutico , Radioisótopos/uso terapéutico , Sinovitis/radioterapia , Animales , Artritis Reumatoide/complicaciones , Quelantes/química , Ácido Cítrico/química , Holmio/farmacocinética , Concentración de Iones de Hidrógeno , Hidroxiapatitas/síntesis química , Inyecciones Intraarticulares , Conejos , Radioisótopos/análisis , Cintigrafía , Sinovitis/diagnóstico por imagen , Sinovitis/etiologíaRESUMEN
Polyphosphonate ligands labelled with radioisotopes decaying by moderate energy beta emission have shown utility as palliative agents for painful bone metastasis. 177Lu (T(1/2)=6.71 d, Ebetamax=497 keV) has radionuclidic properties suitable for use in palliative therapy of bone metastasis. 177Lu was produced at a high specific activity and excellent radionuclidic purity by thermal neutron bombardment of a target prepared from natural Lu. Three polyaminomethylene phosphonate ligands, abbreviated as EDTMP, DTPMP and TTHMP, were synthesized and radiolabelled with 177Lu. Complexation parameters were optimized to achieve maximum yields (97-99.5%). All the complexes were found to retain their stability at room temperature even 14 days after preparation. Biodistribution studies of the complexes were carried out in Wistar rats. All the complexes showed significant bone uptake (6-6.5%/g in tibia at 3 h post-injection (p.i.)) with rapid clearance from blood and minimum uptake in soft tissues. These studies reveal that 177Lu complexes with the synthesized ligands have a potential use in palliative treatment of painful bone metastasis.
Asunto(s)
Neoplasias Óseas/fisiopatología , Lutecio/farmacocinética , Organofosfonatos/síntesis química , Organofosfonatos/farmacocinética , Dolor Intratable/radioterapia , Poliaminas/síntesis química , Poliaminas/farmacocinética , Radiofármacos/síntesis química , Animales , Neoplasias Óseas/secundario , Marcaje Isotópico , Ligandos , Lutecio/química , Lutecio/uso terapéutico , Espectroscopía de Resonancia Magnética , Organofosfonatos/uso terapéutico , Dolor Intratable/etiología , Cuidados Paliativos , Fosforamidas , Poliaminas/uso terapéutico , Control de Calidad , Radioisótopos/uso terapéutico , Radiofármacos/farmacocinética , Radiofármacos/uso terapéutico , Ratas , Ratas Wistar , Espectrofotometría Infrarroja , Distribución TisularRESUMEN
153Sm, an attractive therapeutic radionuclide, was produced by neutron activation of both natural Sm2O3 and 98% enriched 152Sm2O3 targets. The production logistics and radionuclidic purity aspects of 153Sm obtained using both these targets are discussed with respect to the intended end use for metastatic bone pain palliation (MBPP) in terminal cancer patients and radiation synovectomy (RS) of medium size joints. The specific activity of 153Sm obtained was around 11 GBq x mg(-1) (approximately 300 mCi x mg(-1)) and 44 GBq x mg(-1) (approx. 1200 mCi x mg(-1)) from natural and enriched targets, respectively. The level of the long-lived radionuclidic impurity burden in 153Sm obtained from the natural Sm2O3 targets, namely, due to 154Eu (5 Bq x MBq(-1) 153Sm (5 nCi x mCi(-1) 153Sm)) and 155Eu (75 Bq x MBq(-1) 153Sm (75 nCi x mCi(-1) 153Sm)), appears low enough not to pose a problem, both in the palliative treatment of terminal cancer patients (at 1.85-2.22 GBq (50-60 mCi) dose) as well as in RS (at 74 MBq (2 mCi) dose). The 154Eu content in 153Sm from the enriched target was comparable, while, as expected, the level of 155Eu was nearly two orders of magnitude lower. There is a notable overall advantage of 153Sm over the use of 186Re, the other radionuclide of interest for the same purposes.
Asunto(s)
Radiofármacos/química , Samario/química , Composición de Medicamentos , Europio/química , Análisis de Activación de Neutrones , Radioisótopos/uso terapéutico , Radiofármacos/aislamiento & purificación , Radiofármacos/uso terapéutico , Samario/aislamiento & purificación , Samario/uso terapéutico , Espectrometría gammaRESUMEN
The progress in diagnostic nuclear medicine over the years since the discovery of 99mTc is indeed phenomenal. Over 80% of the radiopharmaceuticals currently being used make use of this short-lived, metastable radionuclide, which has reigned as the workhorse of diagnostic nuclear medicine. The preeminence of 99mTc is attributable to its optimal nuclear properties of a short half-life and a gamma photon emission of 140 keV, which is suitable for high-efficiency detection and which results in low radiation exposure to the patient. 99mTcO4-, which is readily available as a column eluate from a 99Mo/99mTc generator, is reduced in the presence of chelating agents. The versatile chemistry of technetium emerging from the 8 possible oxidation states, along with a proper understanding of the structure-biologic activity relationship, has been exploited to yield a plethora of products meant for morphologic and functional imaging of different organs. This article reviews the evolution of 99mTc dating back to its discovery, the development of 99Mo/99mTc generators, and the efforts to exploit the diverse chemistry of the element to explore a spectrum of compounds for diagnostic imaging, planar, and single photon emission computed tomography. A brief outline of the 99mTc radiopharmaceuticals currently being used has been categorically presented according to the organs being imaged. Newer methods of labeling involving bifunctional chelating agents (which encompass the "3 + 1" ligand system, Tc(CO)3(+1)-containing chelates, hydrazinonicotinamide, water-soluble phosphines, and other Tc-carrying moieties) have added a new dimension for the preparation of novel technetium compounds. These developments in technetium chemistry have opened new avenues in the field of diagnostic imaging. These include fundamental aspects in the design and development of target-specific agents, including antibodies, peptides, steroids, and other small molecules that have specific receptor affinity.
Asunto(s)
Radiofármacos , Compuestos de Tecnecio , Huesos/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Quelantes , Corazón/diagnóstico por imagen , Humanos , Infecciones/diagnóstico por imagen , Riñón/diagnóstico por imagen , Ligandos , Neoplasias/diagnóstico por imagen , Radioinmunodetección , Radiofármacos/síntesis química , Receptores de Péptidos/análisis , Receptores de Esteroides/análisis , Compuestos de Tecnecio/síntesis químicaRESUMEN
99mTc eluate in 0.7/0.35 M acetic acid and in 1:1 v/v 0.7 M acetic acid: 0.025 M ammonium acetate (30-40 ml) was conveniently concentrated by passing through a small column of a readily available weak anion exchanger, DEAE cellulose, (200 mg, 6 x 8 mm) and subsequent elution with 3 ml normal saline, with greater than 90% recovery. The quality of pertechnetate thus obtained and its compatibility for preparing 99mTc compounds were satisfactory. This method was successfully applied to the alumina column chromatographic generator produced in-house and to a commercial 99Mo-99mTc generator after extensive clinical use. Potential for much higher concentration factors with compacted anion exchanger cartridges as well as applicability for 188W-188Re generator are discussed.
RESUMEN
99mTc-d,l-HMPAO, an important SPECT agent for imaging cerebral perfusion, suffers from the disadvantage of an inherent instability and its shelf life has been reported to be 30 min. The latter is a harsh constraint and not compatible with Centralized Radiopharmacy procedures. During the attempts to improve upon the stability of 99mTc-d,l-HMPAO, preservation of product as an organic extract into suitable solvents like diethylether, ethylacetate, methylethylketone, chloroform was tried out. Chloroform extraction (yield: >90%) resulted in a product having stability not less than 5 hours. Gentle drying of the chloroform extract and reconstitution in normal saline resulted in quantitative recovery of 99mTc-d,l-HMPAO with acceptable radiochemical purity (>90%). This finding is thus of much significance, especially in the context of centralized large hospital radiopharmacy setting, by rendering convenience and flexibility in scheduling patients.
Asunto(s)
Compuestos de Organotecnecio/aislamiento & purificación , Oximas/aislamiento & purificación , Radiofármacos/aislamiento & purificación , Exametazima de Tecnecio Tc 99m , Estabilidad de Medicamentos , Compuestos Orgánicos , Solventes , EstereoisomerismoRESUMEN
We report on the preparation and evaluation of a large size (jumbo) alumina column (approximately 40 g, 90 x 20 mm) chromatographic generator and post-elution concentration of 99Tcm using a single column of a weak anion exchanger. The generator was eluted with approximately 40 ml of a modified single salt buffer solution of 1:1 v/v 0.025 M or 0.05 M NH4OAc:0.7 M AcOH. This eluate was then passed through a small column of DEAE cellulose, a common weak anion exchanger, to trap 99TcmO4-, which was recovered by elution in 6 ml of normal saline. This amounts to a 5- to 7-fold increase in radioactive concentration (RAC) of 99Tcm, when compared to the RAC on direct elution with normal saline from the same jumbo alumina column generator. The overall yield of 99Tcm was in the range of 70-90%. 99Mo breakthrough was 10(-3)-10(-4)%, radiochemical purity was > 98%, and chemical purity, in terms of Al and Mo content, < 10 ppm each. The compatibility of pertechnetate obtained by this method for preparing 99Tcm labelled formulations such as Tc-MDP and 99Tcm-ethyl cysteinate dimer was found to be satisfactory. These promising results open up the feasibility of using (n, gamma) 99Mo adsorbed on a large (40-60 g) alumina column as a relatively more user-friendly source of 99Tcm in comparison to methyl ethyl ketone extraction, and as a producer-friendly process in comparison to the zirconium molybdate gel method.
Asunto(s)
Compuestos de Tecnecio/aislamiento & purificación , Tecnecio/aislamiento & purificación , Óxido de Aluminio , Cromatografía/instrumentación , Cromatografía/métodos , Cromatografía por Intercambio Iónico/instrumentación , Cromatografía por Intercambio Iónico/métodos , Diseño de Equipo , Indicadores y Reactivos , Pertecnetato de Sodio Tc 99mRESUMEN
The use of beta(-) emitting radionuclides in the control of restenosis in post angioplasty patients is currently under intense investigation at many leading cardiovascular research centers. (32)P coated metallic stents, (192)Ir wire source and balloons filled with an appropriate radionuclide solution such as of (188)Re, attached to catheter are being studied. (166)Ho has comparable radionuclidic properties to that of (188)Re, can be more easily produced and hence is an attractive alternative to (188)Re. Ethylene dicysteine complex of (166)Ho was prepared and its pharmacological behavior studied. Optimum conditions for the preparation of complex with respect to the reaction time, ligand concentration, pH of the reaction mixture as well as reaction temperature were standardized. The stability of the labeled complex at room temperature as well as at 4 degrees C was determined. Biodistribution pattern of the injected complex in Wistar rats was estimated at 10 min, 30 min and 3 h post injection. This study indicated that >90% of the injected (166)Ho-EC complex was excreted in urine within 3 h post injection, with insignificant retention in any major organ. These studies reveal that (166)Ho-EC could be a viable substitute for (188)Re compounds in radioactive liquid-filled balloon IVRT.
Asunto(s)
Cisteína/farmacocinética , Holmio/farmacocinética , Radiofármacos/farmacocinética , Animales , Cromatografía en Papel , Enfermedad Coronaria/radioterapia , Cisteína/análogos & derivados , Cisteína/uso terapéutico , Holmio/uso terapéutico , Humanos , Tasa de Depuración Metabólica , Ratones , Radioisótopos , Radiofármacos/uso terapéutico , Ratas , Ratas Wistar , Distribución TisularRESUMEN
166Ho, with its favourable radiation characteristics of t(1/2) 26.8 h and Ebeta 1.85 and 1.75 MeV, is proposed as a suitable choice for the endovascular radionuclide therapy (EVRT) technique of liquid filled, low pressure balloon angioplasty. 166Ho was produced by the (n,gamma) reaction on a natural Ho2O3 target. The specific activity obtained was approximately 100 mCi x mg(-1) when irradiated at a flux of 2 x 10(13) n x cm(-2) s(-1) for approximately 7 days, and the possible contaminant 166Ho(m) was not detected. 166Ho was easily complexed with diethylenetriaminepentaacetic acid (DTPA) at a ligand to metal molar ratio ([L]:[M]) of 1:1 at room temperature (22-23 degrees C) and a reaction time of a few minutes. The radiochemical purity was >99%, as determined by paper chromatography using a mixture of pyridine, ethanol and water (1:2:4) as solvent. The complex had good stability up to 72 h at 37 degrees C in a serum environment. In a study using Swiss mice > 85% of the injected dose was cleared into the urine within 30 min post-injection, with insignificant retention in any major tissues. The studies show that the 166Ho-DTPA complex could be an alternative to the more expensive and difficult to access 188Re based products for EVRT, and provide adequate uniform radiation dose for the arterial vessel wall under treatment.
Asunto(s)
Angioplastia Coronaria con Balón , Holmio/uso terapéutico , Ácido Pentético/síntesis química , Radiofármacos/uso terapéutico , Animales , Fenómenos Químicos , Química Física , Cromatografía por Intercambio Iónico , Cromatografía en Papel , Holmio/química , Holmio/farmacocinética , Masculino , Ratones , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Distribución TisularRESUMEN
A method of purification of [131I]mIBG (diagnostic dose) by solvent extraction and possibility of its stabilisation by storage in ethyl acetate and chloroform at up to 40 degrees C for not less than 14 days is described. In order to further enhance the utility of this finding, the organic extract was dispensed into vials and dried. Vials containing such dried residue of [131I]mIBG stored at up to 40 degrees C was also found to be stable for at least 10 days. The final product reconstituted as aqueous solution resulted in 90% recovery with 99% radiochemical purity as assessed by previously reported methods, as well as a relatively more rapid paper chromatography method standardised by us. These interesting findings promise simpler and economic packaging besides transport of diagnostic doses of [131I]mIBG.
Asunto(s)
3-Yodobencilguanidina/aislamiento & purificación , Radiofármacos/aislamiento & purificación , 3-Yodobencilguanidina/química , Acetatos , Cloroformo , Estabilidad de Medicamentos , Humanos , Radioisótopos de Yodo , Radiofármacos/química , SolventesRESUMEN
Several agents, such as 188ReO4-, 188Re-MAG3 and 188Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Bearing in mind the risk factor associated with leakage of radioactivity in the event of balloon rupture, the criteria sought in selecting suitable agents for endovascular radiation therapy (EVRT) are rapid clearance and low dose to vital organs. Since 99Tcm labelled ethylene dicysteine (EC) is a well established agent for renal tubular function imaging, the use of 186Re-ethylene dicysteine as a potential agent for prevention of restenosis after angioplasty has been evaluated previously. Therefore, it was of interest to evaluate the applicability of the more potential isotope of rhenium, 188Re, a high energy beta-emitter (Ebetamax = 2.12 MeV) with a suitable T 1/2 = 16.9 h, obtainable carrier-free from the 188W-188Re generator, as an attractive and alternative radionuclide for labelling with L,L-EC. In this paper, the preparation and pharmacological behaviour of the 188Re complex of ethylene dicysteine are reported. The complex can be prepared in high yields (99.5%) under optimized conditions of pH 2-3, at a ligand concentration of 15 mM, 50 microg (0.18 mM) carrier rhenium and using 2 mg x mL(-1) stannous chloride. On storage at 4 degrees C, the RC purity was more than 97% after 48 h when prepared under optimum conditions. Biodistribution studies in Wistar rats showed the desired characteristics of fast blood clearance and low retention of activity in the vital organs (< 2% in intestine, < 1% in stomach, < 0.5% in liver) with a high renal excretion (90.65+/-0.6%) at 3 h post-injection. These results confirm the advantages of using the 188Re-EC complex compared with perrhenate and other rhenium radiopharmaceuticals currently being used in balloons for EVRT.
Asunto(s)
Enfermedad Coronaria/radioterapia , Cisteína/uso terapéutico , Radioisótopos/uso terapéutico , Radiofármacos/uso terapéutico , Renio/uso terapéutico , Angioplastia Coronaria con Balón , Animales , Enfermedad Coronaria/terapia , Vasos Coronarios/efectos de la radiación , Cisteína/análogos & derivados , Cisteína/farmacocinética , Humanos , Radioisótopos/farmacocinética , Radiofármacos/farmacocinética , Ratas , Ratas Wistar , Renio/farmacocinética , Distribución TisularRESUMEN
The complexation of ethylene dicysteine (EC) with 99mTc needs to be carried out at pH 12 to achieve a high radiochemical yield. However, the preparation of the kit at high pH poses difficulties and requires very stringent preparation conditions, as stannous tin, one of the main ingredients in the kit, is unstable at high pH. Hence, an alternative method, involving the transchelation preparation of 99mTc-EC using 99mTc-glucoheptonate (99mTc-GHA) prepared at pH 6.5, was attempted, prompted by the reported success of the preparation of 99mTc-sestamibi (99mTc-MIBI) by this method. The preparation of 99mTc-EC by this method first involved the formation of 99mTc-GHA by the addition of sodium pertechnetate-99mTc to the Sn-GHA kit vial at pH 6.5. 99mTc-EC was formed by the addition of reconstituted EC solution at pH approximately 12 to the preformed 99mTc-GHA. The reaction was allowed to proceed both at room temperature and on a boiling water bath. The pH of the final product was adjusted to pH approximately 7 with 0.5 M phosphate buffer at pH 4-5, without affecting the quality of the product. The urinary excretion of 99mTc-EC prepared by transchelation, tested in mice, was similar to that of directly prepared 99mTc-EC, indicating that the final product prepared by the two methods was the same. The clinical evaluation of the product formulated by the new procedure showed satisfactory findings, comparable with the reports in the literature.
Asunto(s)
Cisteína/aislamiento & purificación , Pruebas de Función Renal/métodos , Riñón/diagnóstico por imagen , Compuestos de Organotecnecio/química , Compuestos de Organotecnecio/aislamiento & purificación , Radiofármacos/aislamiento & purificación , Azúcares Ácidos/química , Adulto , Animales , Quelantes , Niño , Cisteína/análogos & derivados , Cisteína/farmacocinética , Estabilidad de Medicamentos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Ratones , Compuestos de Organotecnecio/farmacocinética , Cintigrafía , Radiofármacos/farmacocinética , Distribución TisularRESUMEN
A simple method of preparation of a new therapeutic colloid, samarium(III) phosphate-(153)Sm (SMPC), is reported involving the reaction of carrier-added (153)SmCl(3) with phosphoric acid. Recovery of the colloid was accomplished by dialysis leading to purification and a radiochemical (RC) yield of more than 90%. The RC purity of purified colloid formulated in isotonic phosphate buffer was more than 99% as assessed by paper chromatography. The product retained its RC purity throughout the period of stability study of 7 days. Complete retention of radioactivity instilled in the rabbit knee joint was observed over the study period of 6 days, with radioactivity in the blood being indistinguishable from the natural background activity. Ninety-six percent of colloidal particles were in the size range of 0.3-2 microm. The promising results demonstrated warrant further studies on SMPC for assessing the suitability for therapy.
Asunto(s)
Radioisótopos/uso terapéutico , Samario/uso terapéutico , Animales , Coloides , Conejos , Ratas , Ratas Wistar , Samario/aislamiento & purificación , Samario/farmacocinética , Distribución TisularRESUMEN
188ReO(4)(-), (188)Re-MAG(3), and (188)Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Because (99m)Tc-labeled ethylene dicysteine (EC) is a well-established agent for renal tubular function imaging, the use of [(188)Re] rhenium-labeled EC as a potential agent for prevention of restenosis after angioplasty is worth evaluation. In this article, the preparation and pharmacological behavior of [(188/186)Re]Re complex of EC are reported. The yield of the Re complex was optimized by varying the parameters of complexation. The complex prepared under the optimized conditions was found to be stable over a period of 7 days when stored at pH 2 and at 4 degrees C. The pharmacological behavior of [(188/186)Re]Re-EC confirms its similarity to (188)Re-MAG(3) and its superiority over (188)ReO(4)(-) for use in endovascular brachytherapy.