1,721,086 research outputs found
Produzione e verifiche di qualità dei radiofarmaci prodotti mediante kit
No full textAnalogamente a tutte le altre preparazioni radiofarmaceutiche, anche i radiofarmaci ottenuti a mezzo kit e i preparati pronti per l'uso sono destinati alla somminisrazione nell'uomo e per questo per essi devono essere garantiti elevati standard qualitativi e di sicurezza, che se da una parte salvaguardiano il paziente da somministrazioni indebite dall'altra assicurano di ottenere per esso la massima efficacia diagnostica o
terapeutica. Partendo dal concetto che la garanzia di allestire prodotti di elevato standard qualitativo è subordinata ad un'approfondita conoscenza delle singole peculiarità dei prodotti, si affida al presente capitolo il compito di descrivere i processi di produzione e verifiche di qualità, con particolare attenzione a quelle che sono le criticità ad essi associabili, poichè ciò consente di porre una sufficiente attenzione sia all'atto produttivo che a quello del controllo
Technetium-99m nitrido radiopharmaceuticals with unprecedented biological properties
Full text linkThe chemical methods for the production of technetium-99m radiopharmaceuticals containing a terminal TcºN triple bond have been established more than a decade ago. From that time, the chemistry of nitrido Tc-99m complexes has provided a highly efficient tool for the design and preparation of novel classes of diagnostic agents, and a number of potentially useful radiopharmaceuticals have been discovered. In particular, nitrido technetium-99m tracers have been developed for heart perfusion imaging. In this short review, the chemical and biological properties of the neutral myocardial perfusion tracer bis(N-ethoxy, N-ethyl-dithiocarbamato) nitrido Tc-99m (TcN-NOEt) will be summarized along with the preparation and preliminary biological evaluation of the first class of monocationic nitrido technetium-99m radiopharmaceuticals exhibiting improved biodistribution properties closer to those expected for an ideal perfusion imaging agent.Os métodos químicos para produção de radiofármacos marcados com tecnécio-99m contendo a ligação tripla terminal TcºN foram estabelecidos há mais de uma década. Desde esta época, a química dos complexos nitridos marcados com 99mTc tem sido uma ferramenta altamente eficiente para o desenho e preparo de novas classes de agentes para diagnóstico e, foi descoberto um número de radiofarmacos potencialmente úteis. Nesta pequena revisão, as propriedades biológicas e químicas do traçador para perfusão miocárdica neutra, o bis(N-etoxi, N-etil-ditiocarbamato) nitrido 99mTc (TcN-NOEt), serão resumidas junto com o preparo e avaliação biológica preliminar da primeira classe de radiofármacos nitrido monocatiônico marcado com tecnécio-99m que exibe melhores propriedades em relação à biodistribuição, mais próximas daquelas esperadas para um agente perfusor ideal para imagens
High-yield synthesis of the terminal Re-188 N multiple bond from generator-produced [(ReO4)-Re-188](-)
No full textA novel procedure for the high-yield preparation of Re-188 radiopharmaceuticals containing a terminal ReN multiple bond is
described. This method involves the reaction of [188Re][ReO4] with N-methyl S-methyl dithiocarbazate (DTCZ), as donor of nitrido
nitrogen atoms, sodium oxalate and SnCl2 to afford a mixture of two intermediate compounds. When this mixture is reacted with the sodium
salt of a dithiocarbamate ligand (L) of the type Na[R2N-C(S)S] (R CH3, CH3CH2, CH3CH2CH2), the formation of the bis-substituted,
neutral complexes [188Re][Re(N)(L)2] is easily obtained in high yield ( 95%). The complexes [188Re][Re(N)(L)2] were characterized by
chromatographic methods, and by comparison with the corresponding complexes prepared at macroscopic level starting from a nonradioactive
rhenium precursor. Biodistribution studies were carried out in rats. Results showed that the complexes [188Re][Re(N)(L)2]
exhibited the same biological behavior of the analogous Tc-99m complexes reported previously. The easy application of the new synthetic
procedure indicates that it could be conveniently employed for preparing a large class of new Re-188 complexes having potential utilization
in nuclear medicine as therapeutic agents. © 2003 Elsevier Inc. All rights reserved
99mTc-labeled FAPI compounds for cancer and inflammation: from radiochemistry to the first clinical applications
No full textBackground: In recent years, fibroblast activating protein (FAP), a biomarker overexpressed by cancer-associated fibroblasts, has emerged as one of the most promising biomarkers in oncology. Similarly, FAP overexpression has been detected in various fibroblast-mediated inflammatory conditions such as liver cirrhosis and idiopathic pulmonary fibrosis. Along this trajectory, FAP-targeted positron emission tomography (PET), utilizing FAP inhibitors (FAPi) labeled with positron emitters, has gained traction as a powerful imaging approach in both cancer and inflammation. However, PET represents a high-cost technology, and its widespread adoption is still limited compared to the availability of gamma cameras. To address this issue, several efforts have been made to explore the potential of [99mTc]Tc-FAPi tracers as molecular probes for imaging with gamma cameras and single photon emission computed tomography (SPECT). Main body: Several approaches have been investigated for labeling FAPi-based compounds with 99mTc. Specifically, the mono-oxo, tricarbonyl, isonitrile, and HYNIC strategies have been applied to produce [99mTc]Tc-FAPi tracers, which have been tested in vitro and in animal models. Overall, these labeling approaches have demonstrated high efficiency and strong binding. The resulting [99mTc]Tc-FAPi tracers have shown high specificity for FAP-positive cells and xenografts in both in vitro and animal model studies, respectively. However, the majority of [99mTc]Tc-FAPi tracers have exhibited variable levels of lipophilicity, leading to preferential excretion through the hepatobiliary route and undesirable binding to lipoproteins. Consequently, efforts have been made to synthesize more hydrophilic FAPi-based compounds to improve pharmacokinetic properties and achieve a more favorable biodistribution, particularly in the abdominal region. SPECT imaging with [99mTc]Tc-FAPi has yielded promising results in patients with gastrointestinal tumors, demonstrating comparable or superior diagnostic performance compared to other imaging modalities. Similarly, encouraging outcomes have been observed in subjects with gliomas, lung cancer, breast cancer, and cervical cancer. Beyond oncological applications, [99mTc]Tc-FAPi-based imaging has been successfully employed in myocardial and idiopathic pulmonary fibrosis. Conclusions: This overview focuses on the various radiochemical strategies for obtaining [99mTc]Tc-FAPi tracers, highlighting the main challenges encountered and possible solutions when applying each distinct approach. Additionally, it covers the preclinical and initial clinical applications of [99mTc]Tc-FAPi in cancer and inflammation
Quality control of Tc-99m radiopharmaceuticals: influence of the generator in growth time on the final radiochemical purity
No full textRadiochemical Puritiy Of 99mTc-HMPAO: some Considerations on Routine Radiopharmaceuticals Preparation
No full textAim. Technetium-99m-d,l-hexameththylpropyleneamineoxime (99mTc-d,l-HMPAO) prepared from the commercially available lyophilized kit , CeretecTM, (GE Healthcare, UK) is used to image regional cerebral blood flow and for in vitro leukocytes labeling. The aim of this work was to study the influence of the nature (pH, plastic ampoules stored away from light sources or glass ampoules) of 0,9% NaCl sodium chloride injection used to dilute generator produced sodium pertechnetate at 1, 2 , 5 mL for the CeretecTM reconstitution on the radiochemical purity and stability of 99mTc-d,l-HMPAO.
Materials and methods. 99mTc-d,l-HMPAO is prepared using commercially available freeze-dried kits according to the procedure specified by the manufacturer. Kits were reconstituted with 1, 2 or 5 mL of fresh (not more 2 h old) generator eluted sodium [99mTc]pertechnetate coming from a generator eluted not more than 24 h in 0,9% NaCl containing 0,074-0,22 GBq/mL. The radioactive concentration was obtained by diluting generator eluted sodium [99mTc]pertechnetate with 0,9% NaCl Sodium Chloride Injection coming from stored away from light sources plastic ampoules and Sodium Chloride Injection from glass ampoules. The radiochemical purity was measured at 0, 15 and 30 min after preparation and was determined by methods specified by the manufacture.
Results. We found no influence on the radiochemical purity and stability ( at 30 min following the preparation) of 99mTc-HMPAO based on the type and the pH of sodium chloride injection used for pertechnetate diluting. RCP values decreased proportionally with the decrease of the final volume of preparation and in particular for 1 mL of diluted pertechnetate, the PCR at 30 minutes following the preparation is less than the required (80%). Finally we found that pH average for 99mTc-d,l-HMPAO is lower than indicated by the manufacturer (9,0-9,8).
Conclusions. In summary in this work we found that instability of the neutral lipophilic 99mTc-d,l-HMPAO complex is faster in reconstituted kits with smaller volumes than 2 mL of pertechnetate, as happens in routine preparations for in vitro leukocyte labeling, and in particular reconstituted kit with volume of 1 mL can’t be used beyond the 15 minutes of preparation. This suggests that any protocols that provide volumes smaller than 2 mL of pertechnetate for the CeretecTM reconstitution should be carefully evaluated in terms of stability of the product. We also noted that the pH average for any categories of preparation is lower than indicated by the manufacturer (9,0-9,8). This does not seem to compromise the stability of the product
LABELLING OF SMALL MOLECULES WITH THE 99mTc-NITRIDO CORE (cap.15)
No full textIn the framework of the project focused on the study of labelling methods of small
biomolecules with novel 99mTc cores, a number of labelling procedures based on the
[99mTc≡N]2+ core have been proposed. It was found that the most useful class of 99mTc
complexes for incorporating small bioactive molecules was that of bis substituted
complexes with bidentate chelating ligands. This class includes both symmetrically and
asymmetrically bis substituted complexes. In symmetrical complexes, two identical
bidentate ligands are coordinated to the same Tc≡N group. Conversely, two different
bidentate ligands bind to the same metal centre in asymmetrical nitrido complexes. In
the paper, a summary of results obtained within the coordinated research project
through the application of the chemistry of 99mTc-nitrido complexes is reported
An alternative method to produce isotopes for medical applications in the framework of the SPES Project: Mo-99 from the UCx target
No full textNew [3+1] Chelating System for Rhenium (V) Nitrido Radiopharmaceuticals
No full textAim. Radionuclide therapy still remains one of the potentially most effective approaches for the treatment of cancer. A common strategy entails the radiolabelling of an appropriate biologically active molecule, such as proteins, peptides or drugs, which is known to selectively target cancerous cells. The usual challenge comes from the need to incorporate the radioactive tag within the structure of the bioactive molecule without affecting its primitive biological properties. This problem becomes more relevant with metallic radionuclides, which constitutes the largest set of radioelements having suitable nuclear properties for therapeutic purposes. At present, the most popular method, dubbed ‘bifunctional approach’, consists of tethering a strong chelating group for the metal to a point of the bioactive molecule that is irrelevant for preserving its biological properties. The resulting bifunctional ligand would act as a bridging backbone between the biomolecule and the metal. The ß-emitting radionuclide Re-188 is considered a very attractive candidate for the development of therapeutic radiopharmaceuticals. Studies were devoted to finding strong chelating systems capable of conferring a high in vivo stability to the resulting complexes. Our group focused on the study of five-coordinated complexes characterized by the presence of a terminal [188Re=N]2+ multiple bond. The aim of this work was to develop mixed-ligand [188Re (N)(SNS)(PCN)] complex [PCN = P(CH2CH2CN)3; SNS= 2-2’-dimercaptodiethylamine, H2SNS =NH(CH2CH2SH)2] and evaluate their stability, essential pre-requisite for the development of target-specific agents for molecular therapy.
Materials and Methods. Reagents required for the preparation of mixed-ligand [188Re (N)(SNS)(PCN)] complex were provided through a two-vial freeze-dried kit formulation (vial A and B). The preparation involves two steps: (1) formation of the [188Re =N]2+ core (Vial A), (2) reaction of this "core" with the H2SNS derivative and the mono-phosphine to afford the “3+1” complex nitrido [188Re (N)(SNS)(PCN)] (vial B). Purification of the complex from excess of reagents and free ligand was carried out by passing the activity through a reversed-phase SepPak cartridge. The radiochemical yield was determined by HPLC chromatography.
Results. The radiochemical yield for the complex 188Re(N)(SNS)(PCN) was found to be in the range 95.2 ± 3.0. Evaluation of stability of all complex in serum and towards transchelation with GSH and cysteine revealed no change in radiochemical purity (RCP) after 48 h of incubation at 37°C.
Conclusion. The new ”3+1” chelating system studied is very stable and obtained in high yield through lyophilized formulations. The tridentate ligand (SNS) can be derivatized for developement of new therapeutic agents.
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New "3+1" chelating system for the development of therapeutic agents labeled with rhenium-188
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