[en] ^99mTc-nitrido complexes of L,L-ethylene dicysteine (^99mTcN-L,L-EC) and ^99mTcN-L,L-ethylene dicysteine diethylester (^99mTcN-L,L-ECD) were prepared and their characteristics compared to those of the respective ^99mTc-oxo complexes. ^99mTcN-L,L-EC and ^99mTcO-L,L-EC migrate to similar extents during electrophoresis at pH 12, but, at pH 6, ^99mTcN-L,L-EC migrates further than ^99mTcO-L,L-EC. Renal excretion of ^99mTcN-L,L-EC is inferior to that of ^99mTcO-L,L-EC, indicating that the TcN-glycine sequence has lower affinity for the renal tubular system. Both ^99mTcO-L,L-ECD and ^99mTcN-L,L-ECD are neutral, but ^99mTcN-L,L-ECD is hydrophilic and shows minimal brain uptake in both mice and the baboon

[en] The symmetrical complexes [^99mTc][TcN(R₂PS₂)₂] [R = CH₃, CH₂CH₃, CH₂CH₂CH₃, CH₂(CH₃)₂], and the unsymmetrical complex [^99mTc][TcN(Me₂PS₂)(Et₂PS₂)] have been prepared, at tracer level, through a two-step procedure involving the preliminary formation of a prereduced technetium nitrido intermediate followed by substitution reaction onto this species by the appropriate dithiophosphinate ligand [R₂PS₂]Na. The chemical identity of the resulting complexes have been established by comparison with the corresponding ⁹⁹Tc-analogs prepared, at macroscopic level, by reacting the complex [⁹⁹TcNCl₄] [n-Bu₄N] (n-Bu = n-butyl) with an excess of ligand in methanol, and characterized by elemental analyses and spectroscopic techniques. The complexes are neutral and lipophilic, and possess a square pyramidal geometry, with an apical Tc N group and two dithiophosphinate ligands spanning the four positions on the basal plane through the four sulfur atoms of the >PS₂ group. In vitro studies showed that these radiopharmaceuticals are stable in solution and that their chemical identity was not altered after incubation with rat blood. Biodistribution studies have been carried out in rats and primates. The results demonstrate that these compounds are significantly retained into the brain of these animals for a prolonged time. Planar gamma camera images have been obtained in monkeys showing a good visualization of the cerebral region. However, the existence of persistent blood activity yields a brain/blood ratio lower than that observed with other ^99mTc-based brain perfusion imaging agents

[en] The synthesis, at tracer level, of two Tc-99m complexes having the same chemical composition and structure, but differing by one electron in the total electron counting, is reported. These compounds have been prepared by reacting [^99mTcO₄]^- with the piperidinium salt of the ligand ferrocenedithiocarboxylate {[Fe(II)(C₅H₄CS₂)(C₅H₅)]^-=FcCS}, in the presence of N-methyl S-methyldithiocarbazate as donor of N^3- groups, and triphenylphosphine or SnCl₂ as reducing agents. The formation of the neutral complex [^99mTc(N)(FcCS)₂] (compound A) and of the monocationic, mixed-valence complex [^99mTc(N)(FcCS) (FcCS*)]⁺ (compound B) {FcCS* [Fe(III)(C₅H₄CS₂)(C₅H₅)]} was obtained in high yield. Both complexes comprise a terminal Tc≡N multiple bond and two FcCS ligands coordinated to the metal center through the two sulfur atoms of the -CS₂ group, but they differ in the oxidation state of one of the two iron atoms of the coordinated FcCS ligands. In complex A, the two Fe atoms are both in the +2 oxidation state, while in B, one Fe atom is in the +2 and the other is in the +3 oxidation state. Thus, B is a mixed-valence Fe(II)-Fe(III) complex. B is easily converted into A by one-electron exchange with various reductants such as triphenylphosphine and excess SnCl₂. Biodistribution studies in rats showed that complexes A and B are mostly retained in lungs and liver without any significant uptake in organs such as heart and brain

[en] A novel class of technetium-99m radiopharmaceuticals showing high heart uptake is described. These complexes were prepared through a simple and efficient procedure, and their molecular structure fully characterized. They are formed by a terminal Tc≡N multiple bond and two bidentate phosphine-thiol ligands [R₂P-(CH₂)_nSH, n=2,3] coordinated to the metal ion through the neutral phosphorus atom and the deprotonated thiol sulfur atom. The resulting geometry was trigonal bipyramidal. Biodistribution studies were carried out in rats. The complexes exhibited high initial heart uptake and elimination through liver and kidneys. The washout kinetic from heart was dependent on the nature of the lateral R groups on the phosphine-thiol ligands. When R=phenyl, heart activity was rapidly eliminated within 10-20 min. Instead, when R=tolyl,cyclohexyl, persistent heart uptake was observed. Extraction of activity from myocardium tissue showed that no change of the chemical identity of the tracer occurred after heart uptake. On the contrary, metabolization to more hydrophilic species occurred in liver and kidneys

[en] The reaction of pertechnetate with the S-methyl ester of dithiocarbazic acid, H₂N-NR-C(=S)SCH₃ (R = H or CH₃), in the presence of HCl and triphenylphosphine, affords the technetium nitrido complex [TcNCl₂(PPh₃)₂] in high yield. Derivatives of S-methyl dithiocarbazate of the type R¹(R²)C=N-NR³-C(=S)SCH₃, where R¹ = o-C₆H₄OH, C₆H₅, or CH₃, R² = H or CH₃, and R³ = H or CH₃, behave as sources of N^3- groups, giving rise to a variety of technetium complexes containing the Tc≡N multiple bond. These reactions apply equally well to the preparation of technetium-99m radiopharmaceuticals containing the Tc≡N group, at the non-carrier-added level of nuclear medicine. (author)

[en] Labelled molecules for human administration are comparable to drugs and hence chosen according to both physicochemical and radioactive criteria. Factors to be considered are the metabolic fate of the vector molecule, its manner of administration and the characteristics of the label, which must be able to fix into the molecule and be detected externally. Different labelling techniques and presentations are reviewed in this article; their choice depends on the nature of the label and the vector

[en] These are simple salts of radioelements produced by nuclear reactions either in nuclear reactors or by cyclotrons. This chapter reviews the different production methods suited to the two techniques. Examples of preparation of some of the most important radioisotopes, together with their medical use, are given for each case. The last part of the chapter is devoted to radioisotope generators, simple systems designed for the separation of radioactive mother-daughter products

No abstract available

[en] This chapter describes the different instruments used to follow and measure the distribution of a radionuclide or a labelled molecule after its introduction into the human body

[en] A major goal of nuclear oncology is the development of new radiolabelled tracers as proliferation markers. Intracellular calcium waves play a fundamental role in the course of the cell cycle. These waves occur in non-excitable tumour cells via store-operated calcium channels (SOCCs). Bis(N-ethoxy, N-ethyldithiocarbamato) nitrido technetium (V)-99m (^99mTcN-NOET) has been shown to interact with L-type voltage-operated calcium channels (VOCCs) in cultured cardiomyocytes. Considering the analogy between VOCCs and SOCCs, we sought to determine whether ^99mTcN-NOET also binds to activated SOCCs in tumour cells in order to clarify the potential value of this tracer as a proliferation marker. Uptake kinetics of ^99mTcN-NOET were measured in human leukaemic HL-60 cells over 60 min and the effect of several calcium channel modulators on 1-min tracer uptake was studied. The uptake kinetics of ^99mTcN-NOET were compared both with the variations of cytosolic free calcium concentration measured by indo-1/AM and with the variations in the SG₂M cellular proliferation index. All calcium channel inhibitors significantly decreased the cellular uptake of ^99mTcN-NOET whereas the activator thapsigargin induced a significant 10% increase. In parallel, SOCC activation by thapsigargin, as measured using the indo-1/AM probe, was inhibited by nicardipine. These results indicate that the uptake of ^99mTcN-NOET is related to the activation of SOCCs. Finally, a correlation was observed between the tracer uptake and variations in the proliferation index SG₂M. The uptake of ^99mTcN-NOET seems to be related to SOCC activation and to cell proliferation in HL-60 cells. These results indicate that ^99mTcN-NOET might be a marker of cell proliferation. (orig.)