ABSTRACT
A single-site prospective open-label clinical study with cyclotron-produced sodium 99mTc-pertechnetate (99mTc-NaTcO4) was performed in patients with indications for a thyroid scan to demonstrate the clinical safety and diagnostic efficacy of the drug and to confirm its equivalence with conventional 99mTc-NaTcO4 eluted from a generator. Methods:99mTc-NaTcO4 was produced from enriched 100Mo (99.815%) with a cyclotron (24 MeV; 2 h of irradiation) or supplied by a commercial manufacturer (bulk vial eluted from a generator). Eleven patients received 325 ± 29 (mean ± SD) MBq of the cyclotron-produced 99mTc-NaTcO4, whereas the age- and sex-matched controls received a comparable amount of the generator-derived tracer. Whole-body and thyroid planar images were obtained for each participant. In addition to the standard-energy window (140.5 keV ± 7.5%), data were acquired in lower-energy (117 keV ± 10%) and higher-energy (170 keV ± 10%) windows. Vital signs and hematologic and biochemical parameters were monitored before and after tracer administration. Results: Cyclotron-produced 99mTc-NaTcO4 showed organ and whole-body distributions identical to those of conventional 99mTc-NaTcO4 and was well tolerated. All images led to a clear final diagnosis. The fact that the number of counts in the higher-energy window was significantly higher for cyclotron-produced 99mTc-NaTcO4 did not influence image quality in the standard-energy window. Image definition in the standard-energy window with cyclotron-produced 99mTc was equivalent to that with generator-eluted 99mTc and had no particular features allowing discrimination between the 99mTc production methods. Conclusion: The systemic distribution, clinical safety, and imaging efficacy of cyclotron-produced 99mTc-NaTcO4 in humans provide supporting evidence for the use of this tracer as an equivalent for generator-eluted 99mTc-NaTcO4 in routine clinical practice.
Subject(s)
Cyclotrons/instrumentation , Radiation Injuries/etiology , Sodium Pertechnetate Tc 99m/adverse effects , Sodium Pertechnetate Tc 99m/pharmacokinetics , Thyroid Diseases/diagnostic imaging , Thyroid Diseases/metabolism , Adult , Aged , Aged, 80 and over , Equipment Design , Female , Humans , Isotope Labeling/instrumentation , Male , Metabolic Clearance Rate , Middle Aged , Organ Specificity , Radiation Injuries/diagnosis , Radiation Injuries/prevention & control , Radionuclide Generators , Radiopharmaceuticals/adverse effects , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity , Sodium Pertechnetate Tc 99m/chemical synthesis , Tissue DistributionABSTRACT
Bone scintigraphy allows the diagnostic of many pathologies related to bone through the intravenous administration of a phosphonate bone marker complexed to 99 metastable technetium (99mTc). The instability of these injectable solutions on contact with air can lead to a mixture of pertechnetate VII (99mTcO4-) and technetium IV (99mTcO2-, xH2O), technetium IV being the only derivative to fix bone. A qualitative control of the purity of these solutions proved to be consequently important before administration. We report here the perfecting of a new chromatographic test based on reverse phase high performance thin layer chromatography (HPTLC). This test, simple, rapid and reproductive allows without ambiguity the detection of 99mTcO4-(VII) and 99mTcO2-(IV), xH2O in hydroxymethylene diphosphonate (HMDP) injectable solutions ready to use.
Subject(s)
Bone and Bones/diagnostic imaging , Radiopharmaceuticals/chemical synthesis , Sodium Pertechnetate Tc 99m/chemical synthesis , Technetium Tc 99m Medronate/analogs & derivatives , Chromatography, High Pressure Liquid , Pharmaceutical Solutions , Radionuclide Imaging , Radiopharmaceuticals/chemistry , Sodium Pertechnetate Tc 99m/chemistry , Technetium Tc 99m Medronate/chemical synthesis , Technetium Tc 99m Medronate/chemistryABSTRACT
We report the synthesis and structural characterization of [UO(2)(ReO(4))(DPPMO(2))(2)][ReO(4)] and [UO(2)(Cl)(DPPMO(2))(2)][Cl] (where DPPMO(2) = bis(diphenylphosphino)methane dioxide). In both complexes, the linear uranyl dication is coordinated to two bidentate DPPMO(2) ligands in the equatorial plane with one coordinated and one non-coordinated anion (either perrhenate or chloride). We have also prepared the pertechnetate analogue, and, through (31)P and (99)Tc NMR, we have shown that the cation, [UO(2)(TcO(4))(DPPMO(2))(2)](+), is stable in solution.
Subject(s)
Organotechnetium Compounds/chemical synthesis , Sodium Pertechnetate Tc 99m/chemistry , Uranium Compounds/chemistry , Anions/chemical synthesis , Anions/chemistry , Chlorides/chemistry , Crystallography, X-Ray , Ligands , Models, Chemical , Organotechnetium Compounds/chemistry , Rhenium/chemistry , Sodium Pertechnetate Tc 99m/analogs & derivatives , Sodium Pertechnetate Tc 99m/chemical synthesis , Uranium Compounds/chemical synthesisABSTRACT
The reduction of ammonium pertechnetate with bis(diphenylphosphino)methane (dppm), and with diphenyl-2-pyridyl phosphine (Ph(2)Ppy), has been investigated. The neutral Tc(II) complex, trans-TcCl(2)(dppm)(2) (1), has been isolated from the reaction of (NH(4))[TcO(4)] with excess dppm in refluxing EtOH/HCl. Chemical oxidation with ferricinium hexafluorophosphate results in formation of the cationic Tc(III) analogue, trans-[TcCl(2)(dppm)(2)](PF(6)) (2). The dppm ligands adopt the chelating bonding mode in both complexes, resulting in strained four member metallocycles. With excess PhPpy, the reduction of (NH(4))[TcO(4)] in refluxing EtOH/HCl yields a complex with one chelating Ph(2)Ppy ligand and one unidentate Ph(2)Ppy ligand, mer-TcCl(3)(Ph(2)Ppy-P,N)(Ph(2)Ppy-P) (3). The cationic Tc(III) complexes, trans-[TcCl(2)(Ph(2)P(O)py-N,O)(2)](PF(6)) (4) and trans-[TcCl(2)(dppmO-P,O)(2)](PF(6)) (5) (Ph(2)P(O)py = diphenyl-2-pyridyl phosphine monoxide and dppmO = bis(diphenylphosphino)methane monoxide), have been isolated as byproducts from the reactions of (NH(4))[TcO(4)] with the corresponding phosphine. The products have been characterized in the solid state and in solution via a combination of single-crystal X-ray crystallography and spectroscopic techniques. The solution state spectroscopic results are consistent with the retention of the bonding modes revealed in the crystal structures.
Subject(s)
Phosphines/chemistry , Radiopharmaceuticals/chemistry , Sodium Pertechnetate Tc 99m/chemistry , Chelating Agents , Crystallography, X-Ray , Indicators and Reagents , Ligands , Magnetic Resonance Spectroscopy , Oxidation-Reduction , Radiopharmaceuticals/chemical synthesis , Sodium Pertechnetate Tc 99m/chemical synthesis , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform InfraredABSTRACT
La L, L-etilendicisteína (L,L-EC) se sintetizó de acuerdo al método de P. Blondeau y colaboradores, con las modificaciones introducidas por R.F.Schneider. Se comprobó su pureza por punto de fusión, espectroscopia de masa, espectroscopia infrarroja, resonancia magnética nuclear y composición centesimal. Se realizaron estudios farmacológicos, esterilidad, apirogenicidad, toxicidad y distribución biológica de animales. La L,L-EC marcado con 99mTc se controló por cromatografía en papel e ITLC-SG. Se inyectó en seres humanos voluntarios normales y con patología renal 55,5-111,0 MBq(1,5-3,0 mCi), realizándose el estudio correspondiente
Subject(s)
Humans , Animals , Cysteine/chemical synthesis , Materials Testing/standards , Sodium Pertechnetate Tc 99m/chemical synthesis , Cysteine , Drugs, Investigational/pharmacokinetics , Drugs, Investigational/chemistry , Drug Evaluation/methods , Isotope Labeling , Biomarkers/urine , Biomarkers/chemistry , Biomarkers/blood , Kidney , Drug Evaluation, Preclinical/methods , Sodium Pertechnetate Tc 99m/analysisABSTRACT
La L, L-etilendicisteína (L,L-EC) se sintetizó de acuerdo al método de P. Blondeau y colaboradores, con las modificaciones introducidas por R.F.Schneider. Se comprobó su pureza por punto de fusión, espectroscopia de masa, espectroscopia infrarroja, resonancia magnética nuclear y composición centesimal. Se realizaron estudios farmacológicos, esterilidad, apirogenicidad, toxicidad y distribución biológica de animales. La L,L-EC marcado con 99mTc se controló por cromatografía en papel e ITLC-SG. Se inyectó en seres humanos voluntarios normales y con patología renal 55,5-111,0 MBq(1,5-3,0 mCi), realizándose el estudio correspondiente
Subject(s)
Humans , Animals , Cysteine/chemical synthesis , Sodium Pertechnetate Tc 99m/chemical synthesis , Materials Testing/standards , Cysteine/diagnosis , Drug Evaluation, Preclinical/methods , Drug Evaluation/methods , Drugs, Investigational/pharmacokinetics , Drugs, Investigational/chemistry , Biomarkers/urine , Biomarkers/chemistry , Biomarkers/blood , Kidney/diagnostic imaging , Isotope Labeling/methods , Sodium Pertechnetate Tc 99m/analysisSubject(s)
Humans , Radionuclide Generators/instrumentation , Isotope Labeling , Radiobiology , Indium Radioisotopes , Radioisotopes , Radionuclide Imaging/standards , Sodium Pertechnetate Tc 99m/chemical synthesis , Technetium Tc 99m Pentetate/chemical synthesis , Technetium Tc 99m Sulfur Colloid/chemical synthesis , Radiobiology/instrumentation , Radiobiology/standards , Radionuclide Imaging/instrumentationSubject(s)
Humans , Radiobiology/methods , Radioisotopes/diagnosis , Sodium Pertechnetate Tc 99m/chemical synthesis , Technetium Tc 99m Sulfur Colloid/chemical synthesis , Technetium Tc 99m Pentetate/chemical synthesis , Radionuclide Generators/instrumentation , Radionuclide Imaging/standards , Isotope Labeling/methods , Indium Radioisotopes/diagnosis , Radionuclide Imaging/instrumentation , Radiobiology/instrumentation , Radiobiology/standardsABSTRACT
A new hexadentate aminethiol ligand (TACNS) derived from triazacyclononane was synthesized and characterized for the development of technetium radiopharmaceuticals. The ligand formed a neutral, lipophilic and stable complex with [99mTc]pertechnetate in the presence of tin(II)tartarate as a reducing agent. The biodistribution of [99mTc]TACNS indicates slight uptake in brain (0.23% ID/organ at 5 min) with a washout at 30 min to 0.14% ID/organ. A small uptake in heart (0.48% ID at 5 min) was also observed. The characterization of [99mTc]TACNS complex using single crystal x-ray analysis and mass spectroscopy has shown that an Sn-N3S3 complex was formed in which tin is oxidized from Sn(II) to Sn(IV). Pertechnetate was incorporated into the complex as counter anion. The nature of the species formed with Tc-99 and "no-carrier-added" [99mTc]pertechnetate is different as confirmed by ratio TLC. From these results, it is demonstrated that sometimes it may be difficult to predict the structure of new technetium radiopharmaceuticals, especially when stannous ion is used as a reducing agent. Moreover, the nature of the chemical species may not be the same at millimolar and at nanomolar levels.
Subject(s)
Heterocyclic Compounds/chemical synthesis , Organotechnetium Compounds/chemical synthesis , Sodium Pertechnetate Tc 99m/chemical synthesis , Sulfhydryl Compounds/chemical synthesis , Animals , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/pharmacokinetics , Isotope Labeling/methods , Ligands , Mice , Mice, Inbred BALB C , Molecular Structure , Organotechnetium Compounds/chemistry , Organotechnetium Compounds/pharmacokinetics , Sodium Pertechnetate Tc 99m/chemistry , Sodium Pertechnetate Tc 99m/pharmacokinetics , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/pharmacokinetics , Technetium/chemistry , Tissue DistributionABSTRACT
En este trabajo se presenta el estudio químico radiofarmacológico y el uso en seres humanos realizado con el "mebrofeini-Tc-99m". La finalidad del trabajo fue determinar el uso potencial de este radiofármaco en seres humanos portadores de distintas entidades clínico patológicas. Para esto, se sintetizó el producto mejorando el rendimiento de reacción, mediante una modificación en la segunda etapa del camino de síntesis, lo que condujo a elevarlo del 70 al 90%. Se determinó la cinética plasmática mediante la circulación extracorpórea realizada en ratas wistar, mientras que la hepática y renal se llevó a cabo en ratones endocriados. Todos los resultados fueron analizados mediante un procesador, obteniéndose las vidas medias plasmáticas y los máximos tiempos de captación (AU)
Subject(s)
Mice , Rats , Animals , Humans , Comparative Study , Liver/diagnostic imaging , Sodium Pertechnetate Tc 99m/diagnosis , Quality Control , Sodium Pertechnetate Tc 99m/chemical synthesis , Cholecystography/methods , Acetanilides/analogs & derivatives , BromineABSTRACT
En este trabajo se presenta el estudio químico radiofarmacológico y el uso en seres humanos realizado con el "mebrofeini-Tc-99m". La finalidad del trabajo fue determinar el uso potencial de este radiofármaco en seres humanos portadores de distintas entidades clínico patológicas. Para esto, se sintetizó el producto mejorando el rendimiento de reacción, mediante una modificación en la segunda etapa del camino de síntesis, lo que condujo a elevarlo del 70 al 90%. Se determinó la cinética plasmática mediante la circulación extracorpórea realizada en ratas wistar, mientras que la hepática y renal se llevó a cabo en ratones endocriados. Todos los resultados fueron analizados mediante un procesador, obteniéndose las vidas medias plasmáticas y los máximos tiempos de captación
Subject(s)
Mice , Rats , Animals , Humans , Liver , Sodium Pertechnetate Tc 99m , Acetanilides/analogs & derivatives , Bromine , Cholecystography , Quality Control , Sodium Pertechnetate Tc 99m/chemical synthesisABSTRACT
TcO-4 is reduced by a mixture of phosphine and thiol ligands to yield cationic complexes in which both ligands are coordinated. Polar and lipophilic properties of the products can easily be controlled by variation of either of the ligands. The yields are always high. Potential heart affinity of the compounds was screened by means of the isolated perfused rat heart. Some of the complexes show significant heart uptake and good retention in the myocardial tissue.
