Technetium Radiopharmaceuticals Research Articles

SERS Investigations of 2-methoxy-2-methylpropylisonitrile (MIBI) and Its Technetium Complex

"Technetium radiopharmaceuticals remain the most widely available and cost-effective compounds used in nuclear medicine imaging. However, exact information regarding the chemical structure of these compounds is scarce. In this study we present a spectroscopic investigation of Hexakis (2-methoxy-2-methylpropylisonitrile) (MIBI) Technetium (99mTc) (99mTc-sestamibi). Surface Enhanced Raman Scattering spectra of the ligand and the Technetium sestamibi complex were recorded. For the later, the measurements were recorded in solution as administered to patients and at different moments from the time of preparation in order to monitor its stability. The information provided by the vibrational characterization of the MIBI ligand allowed us to understand spectroscopic features pertaining to the SERS spectra of the Technetium complex. Keywords: Technetium; radiopharmaceuticals; SPECT; MIBI; SERS. "

Anaphylactic reaction to patent blue dye during sentinel lymph node biopsy in breast cancer

Introduction: Sentinel lymph node biopsy is indicated as gold standard in the surgical treatment of initial breast cancer, presenting as a more conservative approach and preventing total lymphadenectomy. Dyes or technetium radiopharmaceuticals can be used to identify the sentinel lymph node. The most used dyes for the identification of the sentinel lymph node are patent blue and isosulfan blue, and, in lower frequency, methylene blue. However, hypersensitivity reactions to blue dye have been described, estimating its prevalence in 0.6%‒2.7%. The clinical status that characterizes the allergic reaction to the dye can range from mild skin changes to the severe condition, with circulatory collapse. Objectives: To present a severe case of allergic reaction to patent blue in a patient submitted to surgical treatment for breast cancer. Method: This is a case report study based on the analysis of medical records and literature review. Case report: T.L.O.M, female, 49-year old woman, white, married, born in Patos de Minas, MG. Patient diagnosed with Breast cancer, T1N0A0, with indication for sentinel lymph node analysis with blue patent and segmental resection of the tumor. ASA 1 pre-anesthetic evaluation, without history of allergy. The patient was submitted to general inhalation anesthesia and subcutaneous injection in the left breast of 2ml of patent blue, followed by massage. During the anesthetic plan, after 40 minutes of surgery, the patient was hypotensive (40x20 mmHg), with low saturation (ETCO2 28), tachycardia (120 bpm), associated with bluish urticariform papules, and major edema in the ear lobes, being immediately assisted with adrenaline bolus, metaraminol, and decadron. The patient became stable, and it was possible to conclude the procedure. Then, she was referred to the intensive care unit, under sedation and intubated due to the risk of laryngospasm. She evolved hemodynamically stable, and was extubated without intercurrences. Conclusions: A severe anaphylactic reaction to patent blue can risk the life of a patient in an unpredictable manner. Considering this case, it is essential that the entire staff involved in the sentinel lymph node biopsy be aware of the possibility of a hypersensitive reaction to the dye, being prepared to recognize and immediately handle the possible repercussions.

A 99mTc-Labelled Tetrazine for Bioorthogonal Chemistry. Synthesis and Biodistribution Studies with Small Molecule trans-Cyclooctene Derivatives

A convenient strategy to radiolabel a hydrazinonicotonic acid (HYNIC)-derived tetrazine with 99mTc was developed, and its utility for creating probes to image bone metabolism and bacterial infection using both active and pretargeting strategies was demonstrated. The 99mTc-labelled HYNIC-tetrazine was synthesized in 75% yield and exhibited high stability in vitro and in vivo. A trans-cyclooctene (TCO)-labelled bisphosphonate (TCO-BP) that binds to regions of active calcium metabolism was used to evaluate the utility of the labelled tetrazine for bioorthogonal chemistry. The pretargeting approach, with 99mTc-HYNIC-tetrazine administered to mice one hour after TCO-BP, showed significant uptake of radioactivity in regions of active bone metabolism (knees and shoulders) at 6 hours post-injection. For comparison, TCO-BP was reacted with 99mTc-HYNIC-tetrazine before injection and this active targeting also showed high specific uptake in the knees and shoulders, whereas control 99mTc-HYNIC-tetrazine alone did not. A TCO-vancomycin derivative was similarly employed for targeting Staphylococcus aureus infection in vitro and in vivo. Pretargeting and active targeting strategies showed 2.5- and 3-fold uptake, respectively, at the sites of a calf-muscle infection in a murine model, compared to the contralateral control muscle. These results demonstrate the utility of the 99mTc-HYNIC-tetrazine for preparing new technetium radiopharmaceuticals, including those based on small molecule targeting constructs containing TCO, using either active or pretargeting strategies.

New rhenium complexes with ciprofloxacin as useful models for understanding the properties of [99mTc]-ciprofloxacin radiopharmaceutical

Rhenium complexes with the antibiotic ciprofloxacin have been prepared to be studied as models of technetium radiopharmaceuticals. With this aim, the new rhenium complexes 1 {[ReO(Cpf)2]Cl}, 2 {[ReO(CpfH)2]Cl3} and 3 {fac-[Re(CO)3(H2O)(Cpf)]} with ciprofloxacin (CpfH=ciprofloxacin; Cpf=conjugated base of ciprofloxacin) have been synthesised and characterised by elemental analyses, IR, NMR (1H, 19F and 13C CP-MAS) spectroscopy, as well as MS measurements. All spectroscopic data are consistent with the coordination of ciprofloxacin in all these complexes through the carbonyl and the carboxylate oxygen atoms with the formation of a six member chelate ring.The study of a Tc-ciprofloxacin solution by ESI–MS reveals the presence of [TcO(Cpf)2]+ cations, which agrees with the hypothesis that complexes 1 and 2 can be seen as model rhenium complexes of this radiopharmaceutical.Antimicrobial and DNA gyrase inhibition studies performed with complexes 2 and 3 have shown a very similar behaviour between complex 2 and the free antibiotic, whereas complex 3 exhibit a lower antimicrobial activity.Based on a joint analysis of the data reported in the literature and the chemical and biological results obtained in this study, a tentative proposal to explain some aspects of the behaviour of Tc-ciprofloxacin radiopharmaceutical has been made.

Synthesis of multidentate ligands with amido or amino donor groups for the preparation of rhenium and technetium radiopharmaceuticals

A new method to prepare novel semi-rigid multidentate ligands containing nitrogen atom, to coordinate with rhenium and technetium, was established. The method was based on formylation of substituted anilines, followed by Mannich reaction with glycine and paraformaldehyde. The method was very promising to design ligands of various molecular structures (L1–L5) to coordinate with rhenium metal ions. The complexes were prepared through ligand exchange with the complex ReOCl3(PPh3)2, giving new complex of the structure ReOCl3L(1–5). The prepared ligands and complexes were identified by the use of UV–vis, and infrared absorption spectrometric techniques, elemental analysis, molecular weight determination by depression of freezing point. These ligands were labeled with 99mTc pertechnetate, and the labeling efficiency of the complexes was measured using a well type scintillation gamma counter equipment and obtained a good yield.

Preincubation with Sn-complexes causes intensive intracellular retention of 99mTc in thyroid cells in vitro

Technetium radiopharmaceuticals are well established in nuclear medicine. Besides its well-known gamma radiation, (99m)Tc emits an average of five Auger and internal conversion electrons per decay. The biological toxicity of these low-energy, high-LET (linear energy transfer) emissions is a controversial subject. One aim of this study was to estimate in a cell model how much (99m)Tc can be present in exposed cells and which radiobiological effects could be estimated in (99m)Tc-overloaded cells. Sodium iodine symporter (NIS)-positive thyroid cells were used. (99m)Tc-uptake studies were performed after preincubation with a non-radioactive (cold) stannous pyrophosphate kit solution or as a standard (99m)Tc pyrophosphate kit preparation or with pure pertechnetate solution. Survival curves were analyzed from colony-forming assays. Preincubation with stannous complexes causes irreversible intracellular radioactivity retention of (99m)Tc and is followed by further pertechnetate influx to an unexpectedly high (99m)Tc level. The uptake of (99m)Tc pertechnetate in NIS-positive cells can be modified using stannous pyrophosphate from 3-5% to >80%. The maximum possible cellular uptake of (99m)Tc was 90Bq/cell. Compared with nearly pure extracellular irradiation from routine (99m)Tc complexes, cell survival was reduced by 3-4 orders of magnitude after preincubation with stannous pyrophosphate. Intracellular (99m)Tc retention is related to reduced survival, which is most likely mediated by the emission of low-energy electrons. Our findings show that the described experiments constitute a simple and useful in vitro model for radiobiological investigations in a cell model.

Avaliação dos custos para realização de controles de qualidade de radiofármacos marcados com [99mTc]tecnécio em serviços de medicina nuclear no Brasil

OBJETIVO: Estabelecer os custos dos controles de qualidade para os radiofármacos marcados com [99mTc]tecnécio nos serviços de medicina nuclear do Brasil, em atenção às resoluções RDC nº 38/2008 e RDC nº 63/2009 editadas pela Agência Nacional de Vigilância Sanitária. MATERIAIS E MÉTODOS: Foram apurados preços de materiais de consumo, equipamentos e de mão-de-obra para a realização dos controles de qualidade. Os valores foram convertidos para unidades de volume, tempo e outras unidades cabíveis para a determinação do preço unitário. RESULTADOS: O investimento para aquisição de materiais de consumo e equipamentos foi estimado ser de R$ 35.500,00. O custo final para o controle de cada kit variou entre R$ 6,44 e R$ 7,80, dependendo do produto a ser analisado e do profissional selecionado para execução do procedimento. Esses valores podem representar de 0,5% a 10% do valor recebido pelas instituições pela realização dos exames. Na prática, o custo efetivo pode ser menor, uma vez que o produto de um kit pode ser utilizado em diversos pacientes. CONCLUSÃO: Em face do ganho de qualidade e segurança dos pacientes, concluímos que os custos da implantação do programa de controle de qualidade podem ser absorvidos no planejamento financeiro dos serviços de medicina nuclear.

Caution to HPLC analysis of tricarbonyl technetium radiopharmaceuticals: An example of changing constitution of complexes in column

Radio-HPLC is a powerful tool for analyzing radioactive species in radiopharmaceutical chemistry. In this paper, we found an example that the commonly used eluting solvent, acetonitrile, could coordinate with the popular radiopharmaceutical nuclides, technetium-99m, during chromatography. [ 99mTc(CO) 3(H 2O) 3] + and [Re(CO) 3(H 2O) 3] + showed quite different retention time when they were eluted using acetonitrile/water as mobile phase. However, they almost demonstrated the same retention time when they were eluted using methanol/water as mobile phase. Further analysis showed that both [ 99mTc(CO) 3(H 2O) 3] + and [Re(CO) 3(H 2O) 3] + could be changed into [ 99mTc(CO) 3(CH 3CN) 3] + and [Re(CO) 3(CH 3CN) x (H 2O) 3− x ] + during the separation, respectively. Some former works mistook the [ 99mTc(CO) 3(CH 3CN) 3] + for [ 99mTc(CO) 3(H 2O) 3] + when using acetonitrile and water in analysis. Quality control of the radiopharmaceuticals containing metal complex should be careful since HPLC solvent could replace some liable ligand molecules.

A Reverse Perfusion Pattern During Technetium-99m Stress Myocardial Perfusion Imaging Does Not Predict Flow Limiting Coronary Artery Disease

A reverse redistribution pattern during myocardial perfusion imaging is most widely described using thallium (Tl-201), when stress images exhibit greater perfusion than rest. Technetium (Tc-99 m) radiopharmaceuticals may also yield a reverse perfusion (RP) pattern, but its significance is uncertain. This study tested the hypothesis that RP correlates with the presence and location of flow limiting coronary stenosis(es). We reviewed 842 consecutive Tc-99 m tetrofosmin SPECT stress studies performed at a cardiothoracic centre over a 15 month period. 69 (8.2%) demonstrated RP. Thirty-three patients (age 32-79 mean 56, 17 female) had undergone cardiac catheterisation within 12 months of the scan. Correlation was sought between the presence and location of angiographic stenoses and RP pattern. 10/33 (30.3%) had significant (>60%) coronary stenosis(es); 5 single-vessel, 2 two-vessel and 3 three-vessel disease (3VD). Stenosis location correlated poorly with the RP territory (LAD/Anterior 5/17, RCA/Inferior 1/10, Cx/lateral 0/4 (p = 0.57)). Of the 6 patients with a lesion in the RP territory, 3 had 3VD; 2 of these had a simultaneous reversible defect. All 5 patients with previous myocardial infarction had a simultaneous fixed defect. However only 3/12 with co-existent reversible defects had significant disease. The reverse perfusion pattern is a poor predictor of flow limiting coronary disease, and does not correlate with stenosis location in those with significant lesions. Such patients should not undergo invasive investigation purely on the basis of this result.

Contribution of electrospray mass spectrometry for the characterization, design, and development of nitrido technetium and rhenium heterocomplexes as potential radiopharmaceuticals.

Diagnostic nuclear medicine (NM) is among the imaging procedures (together with X-ray, computerized tomography, magnetic resonance, and echography) the clinicians can routinely adopt to image organs or tissues and related disorders. (99m)Tc-based agents are the radiopharmaceuticals of election in diagnostic NM because of the ideal physical properties of the 99mTc nuclide (t1/2 6.01 hr; Egamma 142 keV), low cost, and easy availability through the commercial 99Mo/99mTc generator, and chemical versatility of the element. In the last two decades the synergistic work of clinics, pharmacologists, and coordination chemists has had a tremendous impact in the development of new 99mTc-based radiopharmaceuticals through the recognition of the structure at the molecular level of the agent utilized. This has been achieved by studying the physico-chemical properties of the long-lived 99gTc (t1/2 2.11 x 10(5) year; Ebeta 292 keV) and third-row congener Re isostructural compounds. Electrospray ionization mass spectrometry (ESI-MS) and collision experiments (MS/MS) represent valuable analytical techniques suitable for the characterization of both technetium and rhenium complexes relevant to NM. Unequivocal structural identification of these bioinorganic compounds, either simple coordination complexes ("essential radiopharmaceuticals") or more sophisticated structures carrying bioactive fragments ("receptor-specific" radiopharmaceuticals), can be realized in combination with multinuclear NMR spectroscopy. MS/MS experiments provide useful information on the different metal-ligand bond strength, and comparison of the fragmentation profiles of isostructural technetium and rhenium compounds give additional details on the role played by the metal in determining preferred decomposition channels. The analysis of these data contribute to design novel synthetic strategies for the obtainment of technetium and rhenium compounds relevant to NM. The chemistry underlying the production of a new class of potential radiopharmaceuticals including a terminal nitrogen bond and a mixed coordination sphere comprising heterodiphosphines and/or dithiocarbamates (DTC) is presented in detail together with the ESI-MS and MS/MS investigations.

New routes to bioconjugates of rhenium using the oxobis(dithiolato)rhenate(v) core

The development of the rhenium-188 generator has provided a convenient and economic source of radionuclide for targeted radionuclide therapy of cancer. To exploit this more widely, mild, convenient and efficient methods for stable incorporation of the radionuclide into biomolecules are required. The aim of this work is to exploit the tumour targeting therapeutic radiopharmaceutical [ReO(dmsa)2]− (H2dmsa = meso-dimercaptosuccinic acid), which is easily synthesised in radioactive form and highly stable in vivo, for this purpose. A new efficient synthesis of [ReO(dmsa)2]−, as a single isomer (syn-endo), from perrhenate using acetylhydrazine as reductant, is reported. Dehydration of the two dicarboxylic acid groups of [ReO(dmsa)2]− with dicyclohexylcarbodiimide gives the yellow cyclic dianhydride [ReO(dmsaa)2]− (H2dmsaa = meso-dimercaptosuccinic anhydride) without disrupting the ReOS4 core. As its tetraethylammonium salt, [ReO(dmsaa)2]− was characterised crystallographically as a distorted square pyramidal complex with an axial oxo-group and a syn-endo orientation of the two anhydride rings with respect to this oxo-group. [ReO(dmsaa)2]− reacts with primary and secondary amines including lysine residues of peptides, to form amide-linked conjugates, which were identified by ES-MS. The syntheses are fast, efficient and employ mild conditions, making them readily adaptable for a kit-based approach to rhenium and technetium radiopharmaceuticals.

The solid phase synthesis and NMR spectroscopy of a 99Tc chelate–bombesin derived peptide conjugate

A bombesin derived peptide– 99Tc chelate conjugate was prepared using a solid phase synthetic methodology. The reported approach involved linking a prefabricated bifunctional N 2N′S technetium chelate complex to a resin bound peptide sequence derived from bombesin, which has been shown to bind to the gastrin-releasing peptide (GRP) receptor. The technetium chelate–peptide conjugate was subsequently isolated from the solid support and characterized by electrospray mass spectrometry, HPLC and NMR spectroscopy. The goal of the approach was to develop a versatile solid phase synthetic procedure that would facilitate the future application of modern drug discovery techniques for the development of receptor selective technetium radiopharmaceuticals. Furthermore, the NMR studies of the reported radiometal–peptide conjugate provide an important reference for the characterization of future bombesin-based radiopharmaceuticals.

ChemInform Abstract: Chemistry of Technetium Radiopharmaceuticals. Part 1. Chemistry Behind the Development of Technetium‐99m Compounds to Determine Kidney Function

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Chemistry of technetium radiopharmaceuticals 1: Chemistry behind the development of technetium-99m compounds to determine kidney function

The chemistry behind the development of technetium-99m (Tc-99m) complexes useful for determining renal (kidney) function is discussed. The design of these compounds so that they will be (1) stable in vivo, (2) actively taken up by the kidney and (3) excreted from the body without being metabolized is also discussed. Such issues as the purity of the product (>90% yield required), in vitro stability, and the requirement for ease of preparation are also mentioned. The development and chemistry of commercialized Tc-99m renal function radiopharmaceuticals are covered as are the interplay of the chemistry of Tc-99m and it macroscopic daughter isotope, Tc-99g. Basic technetium chemistry as well as renal physiology and function are also discussed briefly. An attempt is made to highlight areas where further work is needed.

New and Versatile Ternary Ligand System for Technetium Radiopharma-ceuticals: Water Soluble Phosphines and Tricine as Coligands in Labeling a Hydrazinonicotinamide-Modified Cyclic Glycoprotein IIb/IIIa Receptor Antago-nist with 99mTc

New and Versatile Ternary Ligand System for Technetium Radiopharma-ceuticals: Water Soluble Phosphines and Tricine as Coligands in Labeling a Hydrazinonicotinamide-Modified Cyclic Glycoprotein IIb/IIIa Receptor Antago-nist with ^99mTc

New and versatile ternary ligand system for technetium radiopharmaceuticals: water soluble phosphines and tricine as coligands in labeling a hydrazinonicotinamide-modified cyclic glycoprotein IIb/IIIa receptor antagonist with 99mTc.

A hydrazinonicotinamide-functionalized cyclic platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist [cyclo(D-Val-NMeArg-Gly-Asp-Mamb(5-(6-(6-hydrazinonicotin amido) hexanamide))) (HYNIC-tide)] was labeled with 99mTc using tricine and a water soluble phosphine (TPPTS, trisodium triphenylphosphine-3,3',3"-trisulfonate; TPPDS, disodium triphenylphosphine-3,3'-disulfonate; or TPPMS, sodium triphenylphosphine-3-monosulfonate] as coligands. The synthesis of technetium complexes, [99mTc(HYNICtide)(L)(tricine)] (1, L = TPPTS; 2, L = TPPDS; 3, L = TPPMS), can be performed in one or two steps in high yield and with high specific activity (> or = 20,000 Ci/mmol). For example, the reaction of the HYNICtide, [99mTc]pertechnetate, stannous chloride, and tricine at pH 4-5 and room temperature results in the complex [99mTc(HYNICtide)(tricine)2], which reacts with TPPTS (50 degrees C for 30 min) to give complex 1 in > or = 90% yield as determined by radio-HPLC. Complexes 1-3 are formed as equal mixtures of two isomeric forms and are stable for > or = 6 h in the reaction mixture and in dilute solution. Both isomeric forms of complex 1 were found by a platelet-binding assay to contain the 99mTc-labeled HYNICtide and possess biological activity. The composition of these complexes was determined to be 1:1:1:1 for Tc:HYNICtide:L:tricine through a series of mixed ligand experiments on the tracer (99mTc) level. Surprisingly, this composition is maintained over a wide range of relative ligand ratios. The relative bonding capability of the three phosphine coligands to the Tc was determined by spiking various amounts of TPPDS or TPPMS into TPPTS and falls in the order TPPMS > TPPDS > TPPTS. The lipophilicity of the [99m Tc]HYNICtide complexes can be systematically varied by the choice of the phosphine and aminocarboxylate coligands. Using the combination of tricine and a phosphine ligand, HYNIC-derivatized peptides or other small molecules can be labeled with 99mTc in high specific activity and with high stability for potential use as radiopharmaceuticals.

Technetium Radiopharmaceuticals—Fundamentals, Synthesis, Structure, and Development

AbstractTechnetium‐99m radiopharmaceuticals are increasingly finding application in nuclear medicine for scintigraphic and emission tomographic imaging, morphologic description and functional testing of organs. Over 80% of the radiopharmaceuticals currently clinically used are labeled with the short‐lived, metastable nuclide 99mTc, whose nuclear properties are almost optimal with regard to a low radiation exposure of the patient and an effective detection of the emitted γ quanta. 99mTcO can be easily prepared without the use of accelerator systems through generator columns. Most of the 99mTc radiopharmaceuticals are complexes which are synthesized by reduction of 99mTcO in the presence of suitable ligands. To achieve a high organ specificity, some understanding of the relationship between the structure of the diagnostic agent and its organ distribution is necessary. Structure analyses can be carried out on analogous compounds of the long‐lived nuclide technetium‐99g; these compounds are obtainable in weighable quantities. The development of new 99mTc radiopharmaceuticals is a challenge to coordination chemists. The syntheses, molecular structures, and applications of the most important 99mTc radiopharmaceuticals will be described in this review, and current directions and tendencies of the development will be shown.

Technetium 94m-labeled methoxyisobutyl isonitrile: dosimetry and resting cardiac imaging with positron emission tomography.

Development of a positron-emitting form of technetium has allowed the imaging of technetium radiopharmaceuticals with positron emission tomography (PET). We used 94mTc to compare the distribution of the myocardial perfusion agent sestamibi at rest with the conventional PET perfusion tracer 13N-labeled ammonia (13N-ammonia). Dosimetry calculations were performed with the known whole-body distribution of 99mTc-labeled sestamibi. Dynamic PET imaging of 13N-ammonia and 94mTc-labeled sestamibi (94mTc-sestamibi) for 32 minutes was performed in eight patients with previous myocardial infarction. Initial myocardial and extramyocardial distribution of 94mTc-sestamibi was compared with that of 13N-ammonia by qualitative and quantitative analysis. Quantitative comparison of the two tracers was performed with region-of-interest analysis and circumferential profiles. Qualitatively, the cardiac distribution of the tracers was similar in normal and infarcted myocardium. A decrease in the definition of the epicardial and endocardial borders of the heart was seen with 94mTc-sestamibi, presumably because of the lower dose of radionuclide injected. Quantitatively, there was no difference in infarct size, defined prospectively as tracer activity less than 20% of maximum activity for the section, between the two tracers. Circumferential profile analysis with 12-degree radial sections similarly demonstrated no difference in regional cardiac distribution of the tracers. These results revealed no significant difference in myocardial uptake compared with 13N-ammonia suggesting that the myocardial uptake of sestamibi correlates with that of myocardial perfusion.

Preparation, characterization and electrochemical properties of technetium(II) complexes with 1,2-bis(diethylphosphino)ethane (depe) and dithiocarbamate ligands. Single-crystal structural analysis of [Tc((CH 3) 2NCS 2)(DEPE 2)](PF 6)

Three technetium(II) complexes of the type [Tc(dtc)(DEPE) 2] + have been newly prepared and isolated, where DEPE denotes 1,2-bis(diethylphosphino)ethane and dtc represents dimethyldithiocarbamate (dmdc), diethyldithiocarbamate (dedc) or pentamethylenedithiocarbamate (pmdc). The complexes have been characterized by elemental analysis, UV-vis spectroscopy. FAB mass spectroscopy, electrochemistry and high performance liquid chromatography. Bidentate coordination of the dithiocarbamate ligand is confirmed by a single-crystal structural analysis of the prototypical complex [Tc(dmdc) (DEPE) 2](PF 6). Bond lengths around the approximately octahedral technetium(II) centre are TcS = 2.449(6), TcP ( trans to P) = 2.43(2) and TcP ( trans to S) = 2.38(2) Å. The TcP length trans to the sulphur atom is significantly shorter than that which is trans to a phosphorus atom. Electrochemical measurements for the [Tc(dtc)(DEPE) 2] + complexes show a reversible technetium(II/I) couple between −0.517 and −0.544 V (vs Ag/AgCl) and another reversible technetium(III/II) couple ranging from +0.298 to +0.312 V (vs Ag/AgCl) in 0.5 M TEAP/DMF. The relevance of this chemistry to the design and development of new technetium radiopharmaceuticals is briefly discussed.

Synthesis, characterization and biodistribution of a new hexadentate aminethiol ligand labeled with Tc-99m

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-N 3S 3 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.