Tricarbonyltechnetium (I) labelled ligands with nso donor atom set: in vitro and in vivo evaluation

There is an increasing interest for the 99mTc labelling of biomolecules by using bifunctional chelating agents. To find new ligand, which can be linked to the small biomolecules and coordinated with technetium-99m tricarbonyl complexes, is a challenging task. The investigated NSC and NSC5 ligands allow the preparation 99mTc(I) stable complexes in high yield. The 99mTc complexes were characterized by comparing their HPLC profiles with those of the respective Re(I) compounds. Biodistribution and stability studies were carried out, including challenge with histidine. These complexes also proved to be stable in vivo and showed a very good biological behaviour. The radiochemical and biological features of the novel 99mTc complexes, as well as, the nature of the ligands, make them very promising candidates for labelling of tumour specific biomolecules.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

99mTc-hexakis-(2-metoxy-isobutyl-isonitrile) ( 99mTc-MIBI) a new myocardial imaging agent: synthesis of MIBI, optimising conditions for radiolabelling with 99mTc at high radiochemical purity and in vivo behavior

99mTc-MIBI is a promising radiopharmaceutical for myocardial perfusion imaging agent, but it has also shown good results in identifying several types of tumors, such as breast, lung and thyroid cancers. It is a lipophilic, cationic technetium (1) complex. In this paper a complete study on the synthesis of 2-metohy-isobutyl-isonitrile (MIBI) as well as a formulation of a lyophilized kit for labeling with 99mTc is presented. Investigation on effective factors as well as finding out the optimum parameters to obtain the highest labelling efficiency and radiochemical purity of 99mTc-MIBI complex were performed. The radiochemical purity of the labelled preparation was high (>95%). Biodistribution study performed in health male Wistar rats showed satisfactory biokinetics results. 99mTc-MIBI was accumulated in sufficient amount into the hearth tissue for myocardial perfusion imaging. MIBI in kit formulation was found to be stable and also safe for administration.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Imaging in situ breast carcinoma (with or without an invasive component) with technetium-99m pentavalent dimercaptosuccinic acid and technetium-99m 2-methoxy isobutyl isonitrile scintimammography

INTRODUCTION: The aim of the study was to retrospectively define specific features of the technetium-99m pentavalent dimercaptosuccinic acid ((99m)Tc-(V)DMSA) and technetium-99m 2-methoxy isobutyl isonitrile ((99m)Tc-Sestamibi [(99m)Tc-MIBI]) distribution in ductal breast carcinoma in situ and lobular breast carcinoma in situ (DCIS/LCIS), in relation to mammographic, histological and immunohistochemical parameters. MATERIALS AND METHODS: One hundred and two patients with suspicious palpation or mammographic findings were submitted preoperatively to scintimammography (a total of 72 patients with (99m)Tc-(V)DMSA and a total of 75 patients with (99m)Tc-Sestamibi, 45 patients receiving both radiotracers). Images were acquired at 10 min and 60 min, and were evaluated for a pattern of diffuse radiotracer accumulation. The tumor-to-background ratios were correlated (T-pair test) with mammographic, histological and immunohistochemical characteristics. RESULTS: Histology confirmed malignancy in 46/102 patients: 20/46 patients had DCIS/LCIS, with or without coexistent invasive lesions, and 26/46 patients had isolated invasive carcinomas. Diffuse (99m)Tc-(V)DMSA accumulation was noticed in 18/19 cases and (99m)Tc-Sestamibi in 6/13 DCIS/LCIS cases. Epithelial hyperplasia demonstrated a similar accumulation pattern. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value for each tracer were calculated. Solely for (99m)Tc-(V)DMSA, the tumor-to-background ratio was significantly higher at 60 min than at 10 min and the diffuse uptake was significantly associated with suspicious microcalcifications, with the cell proliferation index ≥ 40% and with c-erbB-2 ≥ 10%. CONCLUSION: (99m)Tc-(V)DMSA showed high sensitivity and (99m)Tc-Sestamibi showed high specificity in detecting in situ breast carcinoma ((99m)Tc-(V)DMSA especially in cases with increased cell proliferation), and these radiotracers could provide clinicians with preoperative information not always obtainable by mammography

Current status of imaging infections with radiolabeled anti-infective agents

Infection specific radiopharmaceuticals can be used for diagnosis, decision-making in therapy and treatment follow-up. Research has been ongoing to develop infection specific markers since clinically used tracers cannot discriminate between infection and inflammation. A specific radiopharmaceutical for infection imaging should satisfy the following criteria: high and specific uptake at the infection site, rapid infection detection and background clearance, minimal accumulation in non-target tissues, low toxicity, zero immune response and especially the ability to differentiate infection from sterile inflammation. Radiolabeled anti-infective agents can fulfill the majority of these requirements. Technetium-99m (99mTc) labeled antibiotics have potential to differentiate sterile inflammation from infection. There are numerous studies reporting the use of radiolabeled antibacterial and antifungal agents for infection detection. Other promising agents are antimicrobial peptides (AMPs) since they preferentially bind to bacteria membranes instead of those of mammalian cells thus distinguishing between infection and sterile inflammation. Synthetic AMPs derived from human natural peptides offers possibility for studying the effects of polymerization and substituting the amino acid sequence to design a specific micro-organism seeking tracer. 99mTc-labeled anti-infectives are ideal as infection-seeking agents because of its direct and fast accumulation. Clinical studies already undertaken and further evaluation with different pathogen types such as viruses, fungi, parasites and intracellular pathogens in humans will improve the potential of these compounds. Radiochemical techniques for labeling anti-infectives have been developed to optimize biodistribution and targeting properties of tracers. An important issue is the technetium-99m specific coordination site in the anti-infective molecule and its chemical and biochemical characterization. © 2009 Bentham Science Publishers Ltd

Chemical and biological evaluation of Tc-99m (CO)(3) and Tc-99m complexes of some IDA derivatives

The confirmation that N-substituted imidodiacetic acids, as small and simple ligand systems containing amines and carboxylic acids, could be coordinated to the tricarbonyl core and form inert complexes with [Tc-99m (CO)(3)(H2O)(3)](+). is demonstrated. The HPLC quality control results of Tc-99m-carbonyl tagged IDA molecules, performed by gradient HPLC, have shown that HIDA, EHIDA and p-butyl-IDA form complexes with [Tc-99m(CO)(3)(H2O)(3)](+), with a labeling yield of similar to90% for each of Tc-99m(CO)(3) IDA derivatives. However, the changes in the structure of labeled compounds, e.g., EHIDA, influence the changes in the biological behavior. In comparison with Tc-99m-EHIDA, the biliary excretion of Tc-99m(CO)(3) EHIDA was lower, but the urinary excretion higher

Crystal structure of fac-aqua[(E)-4-(benzo[d]thiazol-2-yl)-N-(pyridin-2-ylmethylidene)aniline-κ2N,N′]tricarbonylrhenium(I) hexafluoridophosphate methanol monosolvate

In the title compound, fac-[Re(C19H13N3S)(CO)3(H2O)]PF6·CH3OH, the coordination environment of the ReI atom is octahedral with a C3N2O coordination set. In this molecule, the N,N′ bidentate ligand, (E)-4-(benzo[d]thiazol-2-yl)-N-(pyridin-2-ylmethylidene)aniline, and the monodentate aqua ligand occupy the three available coordination sites of the [Re(CO)3]+ core, generating a `2 + 1' mixed-ligand complex. In this complex, the Re—C bonds of the carbonyl ligands trans to the coordinating N,N′ atoms of the bidentate ligand are longer than the Re—C bond of the carbonyl group trans to the aqua ligand, in accordance with the intensity of their trans effects. The complex is positively charged with PF6− as the counter-ion. In the structure, the complexes form dimers through π–π intermolecular interactions. O—H...O and O—H...N hydrogen bonds lead to the formation of stacks parallel to the a axis, which further extend into layers parallel to (0\overline{1}1). Through O—H...F hydrogen bonds between the complexes and the PF6−counter-anions, a three-dimensional network is established

Crystal structure of fac-tricarbonyl(quinoline-2-carboxylato-κ2N,O)(triphenylarsane-κAs)rhenium(I)

In the title compound, [Re(C10H6NO2)(CO)3{As(C6H5)3}], the coordination environment of ReI is that of a distorted octahedron. Three coordination sites are occupied by three carbonyl groups in a facial arrangement and the remaining three sites by triphenylarsane and deprotonated quinaldic acid in As-mono- and N,O-bidentate fashions, respectively. In the crystal, the complexes are linked through weak C—H...O hydrogen bonds, forming a three-dimensional network. It worth noting that, as far as we know, this complex is the first ReI triphenylarsane tricarbonyl compound to be reported

Convenient route leading to neutral fac-M(CO)3(NNO) complexes (M = Re, 99mTc) coupled to amine pharmacophores

The synthesis and characterization of three neutral tricarbonyl fac-M(CO)3(NNO) (M = Re, 99mTc) complexes based on the picolylamine N,N-diacetic acid (PADA) ligand is reported. One of the two carboxylate groups of the PADA ligand is efficiently and conveniently derivatized with an amine nucleophile through the use of the PADA anhydride. In this work, aniline, benzylamine and pyrrolidine were used as model amine nucleophites. The rhenium complexes were synthesized using the [NEt 4]2[Re(CO)3Br3] precursor and fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography. The analogous technetium-99m complexes were also prepared quantitatively using the (99mTc(CO)3(H2O) 3]+ precursor. The reaction scheme presented for the synthesis of the fac-M(CO)3(NNO) (M = Re, 99mTc) complexes can be applied to the development of target-specific radiopharmaceuticals because, in principle, any bioactive pharmacophore bearing an amine group can be used in the place of the model amine nucleophiles. © 2008 American Chemical Society

Solid-phase synthesis of a peptide derivative of thymosin alpha1 and initial studies on its 99mTc-radiolabelling

A derivative (1) of the immunopotentiating 28-peptide thymosin alpha1 has been especially designed, so that it can be 99mTc-radiolabelled, and synthesized following the Fmoc solid-phase peptide synthesis approach. Derivative 1 contains the N-terminal fragment Tα1[1-14] as a bioactive segment, at the C-terminus of which a 99mTc-chelating moiety consisting of Nα,Nα-dimethylglycine, serine and cysteine is linked through the Nε-amino group of a 'bifunctional' lysine residue; the latter is indirectly anchored on the solid-phase peptide synthesis resin through 6-aminocaproic acid (dmGSCK{N ε-Tα1[1-14]}Aca). Synthetic derivative 1 was obtained at high overall yield (approximately 35%) and purity (>95%) and shown to be efficiently radiolabelled with 99mTc, thus resulting in the first, to our knowledge, so far reported 99mTc-radiolabelled derivative of thymosin alpha1, which may be eventually used as a specific molecular tool for the in vitro/in vivo study of the mode of action of the parent bioactive peptide. © 2007 The Authors