[en] A novel procedure for the high-yield preparation of Re-188 radiopharmaceuticals containing a terminal Re≡N 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 non-radioactive 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

[en] New Tc-99m radiopharmaceuticals with the ligand (o-hydroxyphenyl)diphenylphosphine have been prepared and their biodistributions evaluated in rats. The monoxo Tc(V) complex [^99mTc(O)Cl(PO)₂], the Tc(IV) complex [^99mTc(OH)₂(PO)₂], the Tc(III) complex [^99mTc(PO)₃], and the nitrido Tc(V) complex [^99mTc(N)(PO)₂] have been characterized by TLC and HPLC chromatography, and their chemical structure elucidated by comparison with the corresponding complexes obtained using the β-emitting isotope Tc-99g. Biodistribution studies of these complexes have been carried out in rats

[en] A new efficient approach for the preparation of ¹⁸⁸Re radiopharmaceuticals starting from [¹⁸⁸ReO₄]^-, produced at a carrier-free level through the ¹⁸⁸W/¹⁸⁸Re generator system, is described. The reaction procedure was based on the combined action of different reagents and has been applied in detail to the preparation of the therapeutic agent ¹⁸⁸Re(V)-DMSA (H₂DMSA [meso-2,3-dimercaptosuccinic acid]). The most efficient combination required the use of SnCl₂, oxalate ions, and γ-cyclodextrin. These were reacted with [¹⁸⁸ReO₄]^- and H₂DMSA to afford the final radiopharmaceutical in high radiochemical purity, at room temperature, and in weakly acidic solution. The role played by the various reagents in the reaction was investigated. It was found that SnCl₂ behaved as the actual reducing agent, whereas oxalate and γ-cyclodextrin greatly enhanced the ease of reduction of [¹⁸⁸ReO₄]^- through the action of two hypothetical mechanisms. In the first step of the reaction, oxalate ions gave rise to the formation of Re(VII) complexes with the concomitant expansion of the coordination sphere of the metal. This process strongly favored the electron transfer between Sn²⁺ and Re⁺⁷ centers, giving rise to intermediate reduced rhenium complexes. These species were further stabilized by the formation of transient host-guest aggregates with γ-cyclodextrin and finally converted into ¹⁸⁸Re(V)-DMSA through simple replacement of the coordinated ligands by H₂DMSA

[en] The iodinated oil lipiodol is commonly used as a carrier for in situ delivery of drugs or radioactivity to hepatic tumors. Recently, we reported a new kit formulation for high-activity labeling of lipiodol with the β-emitting radionuclide Re-188. Since the whole preparation involves different steps and complex manipulations of high-activity samples, we describe here an automated synthesis module that allows the easy preparation of sterile and pyrogen-free samples of Re-188 lipiodol ready to be administered to the patient. Important advantages include the possibility to incorporate high Re-188 activity into the lipiodol hydrophobic phase and a sharp reduction of radiation exposure of the operator assisting the labelling procedure. Application of this modular reaction system could be also extended to the preparation of other Re-188 radiopharmaceuticals and to compound labelled with different β-emitting therapeutic radionuclides.

[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] The octapeptide D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-NH₂ ([D-Ala¹]TNH₂), an analog of peptide T (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH) associated with CD₄/T₄ receptors involved in human immunodeficiency virus infection, was combined with the chelating polyazamacrocycle 1,4,8,11-tetraazacyclotetradecane (cyclam) to afford the bifunctional ligand cyc-[D-Ala¹]TNH₂. This was then reacted with [^99mTcO₄]^- and Sn²⁺ to yield the monocationic complex [^99mTc(O)₂(cyc-[D-Ala¹]TNH₂)]⁺. Biological activity of both the cyclam-peptide conjugate and the resulting Tc-99m complex were evaluated by measuring their chemotactic indexes. Results showed that N-cyclam acylation and subsequent labeling with Tc-99m of [D-Ala¹]TNH₂ were tolerated, and both cyc-[D-Ala¹]TNH₂ and [^99mTc(O)₂(cyc-[D-Ala¹]TNH₂)]⁺ retained the high chemotactic capacity of the original octapeptide. Biodistribution of the Tc-99m complex was carried out in rats. Fast blood clearance and no accumulation in organs of interest were observed

[en] A novel class of Tc-99m complexes able to cross the blood brain barrier has been investigated and described here. These compounds are formed by reacting the bis-substituted nitride precursors [^99mTc(N)(PS)₂] (PS phosphino-thiol ligand) with triethylborane (BEt₃) under strictly anhydrous conditions and using non-aqueous solvents. The molecular structure of these tracers was not fully established, but preliminary experimental evidence suggests that they result from the interaction of the Lewis base [^99mTc(N)(PS))₂] with the Lewis acid BEt₃, which leads to the formation of the novel -B-N≡ Tc- adduct. After purification and recovery in a physiological solution, the new borane-nitride Tc-99m derivatives were injected in rats for evaluating their in vivo biological behavior. Results showed a significant accumulation in brain tissue, thus indicating that these complexes are capable of penetrating the intact blood brain barrier. Uptake in the central nervous system was confirmed by imaging the distribution of activity on the integrated living animal using a YAP(S)SPECT small animal scanner. (author)

[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

No abstract available

[en] The chemical methods for the production of technetium 99 m radiopharmaceuticals containing a terminal Tc identical to N triple bond have been established more than a decade ago. From that time, the chemistry of nitrido Tc 99 m 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 99 m 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 99 m (TcN-NOEt) will be summarized along with the preparation and preliminary biological evaluation of the first class of monocationic nitrido technetium 99 m radiopharmaceuticals exhibiting improved biodistribution properties closer to those expected for and ideal perfusion imaging agent. (author)