Preparation,quality control and physico-chemical properties of <Superscript>99m</Superscript>Tc-BAT-AV-45

One novel styrylpyridine derivatives(AV-45) coupled with ^99mTc complex was synthesized. ^99mTc-BAT-AV-45 was prepared by a ligand exchange reaction employing sodium glucoheptonate, and effects of the amount of ligand, stannous chloride, sodium glucoheptonate and pH value of reaction mixture on the radiolabeling yield were studied in details. Quality control was performed by thin layer chromatography and high performance liquid chromatography. Besides the stability, partition coefficient and electrophoresis of ^99mTc-BAT-AV-45 were also investigated. The results showed that the average radiolabeling yield was (95 ± 1%) and ^99mTc-BAT-AV-45 with suitable lipophilicity was stable and uncharged at physiological pH.     

Chromatographic and biological comparison of99mTc-DMSA prepared by direct labelling and ligand exchange reaction

^99mTc-dimercaptosuccinic acid /DMSA/ is one of the most favourable agents used for renal scintigraphy. This radiopharmaceutical was prepared in two different ways: by direct labelling of tin/II/-dimercaptosuccinic acid and by ligand exchange reaction from^99mTc-gluconate at tracer concentration of technetium under acidic condition. The complexes formed were compared using paper chromatography, thin layer chromatography, gel filtration and electrophoresis. Their biodistribution was studied on rats.     

Reaction of [TcNCl4]− with ethylenediamine-N,N'-diacetic acid ligand

The reaction of [^99mTcNCl₄]^– with ethylenediamine-N,N'-diacetic acid (ENDA) has been studied. Starting from [^99mTcNCl₄]^– prepared according to the method of Apparu et al.6, the exchange reaction with ENDA in the presence of stannous tartrate led to the formation of an anionic^99mTcN-ENDA complex. The labeling yield was about 90% at pH values of 10.5 and 6.5. In the absence of the reducing agent the formation of^99mTcO₄ ^– is reflected in the decrease of the complex yield. The exchange reaction of [⁹⁹TcNCl₄]^– with ENDA at pH 6.5 and in the absence of a reducing agent resulted in the formation of the anionic⁹⁹TcN-ENDA complex and⁹⁹TcO₄ ^–. The spectrophotometric characteristics (UV-vis. and IR) of the pure complex are similar to those of some tcN²⁺-complexes with amine ligands. The electrophoretic and chromatographic behaviors of^99mTcN- and⁹⁹TcN-ENDA anions are identical; this proves the formation of the same complex with both radionuclides.     

Labeling of polyaminomacrocyclic ligands BY99mTcO 4 − reduction and exchange reactions

The cationic^99mTc-complexes of 1,4,8,12-tetraazacyclopentadecane (15-ane-N₄), 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane (Me₄cyclam) and 1,4,7,10,13,16-hexaazacyclooctadecane (hexacyclen) are obtained in yields higher than 80% by^99mTcO ₄ ^– reduction at pH 12. The electrophoretic and chromatographic analyses show that these ligands form structurally similar complexes. Efficient labeling of 15-ane-N₄ (>95%) is obtained by the exchange reaction with^99mTc-citrate,^99mTc-ENDA and^99mTc-HBA at pH 12. The labeling yield of hexacyclene is 70% and 85% following the reaction with^99mTc-ENDA and^99mTc-HBA and^99mTc-citrate, respectively. The labeling of Me₄cyclam is very poor (about 10%) except starting from^99mTc-citrate (55%). The results are compared wint the available data for well characterized [TcO₂L]⁺ complexes.     

Organic Synthesis and Technetium-99m Labeling of Some Amino-Phenol Ligands

We reported the synthesis and labeling of one tetradentate and two pentadentate amino-phenol ligands with technetium-99m by the direct pertechnetate addition and by ligand exchange methods. Labeling by direct pertechnetate addition was attended by adding pertechnetate eluate to the ethanolic solution of the amino-phenol ligands at pH 9. Stannous chloride dihydrate was used as reducing agent. Exchange studies were carried out via the use of the following ^99mTc-chelates: ^99mTc-DTPA, ^99mTc-gluconate, ^99mTc-tartrate and ^99mTc-citrate complexes. Ligand exchange method was achieved by incubation the ligand solutions with ^99mTc-co-ligands complexes in 0.05M bicarbonate buffer pH 9. At this pH value the ^99mTc-co-ligands dissociated and the more stable new ^99mTc-ligands were formed with high radiochemical yield 95%. The radiochemical yield of ^99mTc-labeled amino-phenol ligands were estimated by solvent extraction, electrophoresis and HPLC methods. The produced technetium-99m amino-phenol complexes were neutral, lipophilic and stable during the period of 24 hours.     

99mTc complexes of 1,3-propanedithiol derivatives

The labelling of 1,3-n alkylpropanedithiols and of 15-/1,3-dimercapto 2-propyl/ pentadecanoic acid by^99mTc has been performed by an exchange reaction with the hexachlorotechnetate ion^99mTcCl ₆ ^2– and by reduction of^99mTcO ₄ ^– with Sn/II/ in the presence of the ligand. The biological distribution of the exotechnetium complexes obtained by the latter method in mouse does not reveal a high tropism of these labelling compounds in relation to a particular tissue.     

Isotope exchange between 12-molybdocerate(IV) and sodium molybdate-99Mo in aqueous media

12-molybdocerate(IV) gel labelled with⁹⁹Mo has been prepared via isotope exchange between a column of inactive molybdate matrix and a mobile solution of⁹⁹-Mo-sodium molybdate(VI) in 0.1 mol·dm^–3 HNO₃. The composition and nature of the reaction mixture, concentration of Mo(VI) in the reactants, reaction temperature and/or drying temperature of the gel matrix on the exchange yeild of⁹⁹Mo and time of reaction are explored using the batch equilibration and/or the chromatographic column methods. The obtained material is evaluated for use in preparation of elution-type⁹⁹Mo-^99mTc generators.     

Synthesis of <Superscript>99m</Superscript>Tc-pefloxacin: A new targeting agent for infectious foci

Summary This investigation focused on the labeling of pefloxacin, a fluoroquinolone antibacterial agent, with ^99mTc to form ^99mTc-pefloxacin complex. The labeling process was done by direct addition of pertechnetate in isotonic solution to Sn-pefloxacin solution. The labeling technique is effective, as a high labeling yield (98%) was obtained after 30-minute reaction time. Different factors were found that influenced this labeling reaction: 0.5 mg pefloxacin or more must be used to prevent the formation of colloids in the reaction medium. Fifty micrograms of stannous chloride dihydrate were found to be sufficient to reduce all pertechnetate with activity ranging from 37 to 3700 MBq without the detection of free pertechnetate or colloids in the reaction mixture. The pH of the reaction medium was found to play an important role in the labeling process. The labeling reaction proceeds well at neutral pH (pH 6) but at acidic pH value (pH 4 or below) the yield of ^99mTc-pefloxacin complex decreased markedly to a labeling yield of 5%. The reaction mixture must be heated to 100 °C in an oil bath to enhance the formation of the ^99mTc-pefloxacin complex. The biodistribution data show that ^99mTc labeled pefloxacin was retained in infectious focus. The retention was specific since the abscess uptake of ^99mTc-pefloxacin remained high as compared to the uptake of aseptic foci at 24-hour post injection. Also, the clearance of the tracer from other tissues is rapid on the contrary to its clearance from the septic focus. This supports the hypothesis that ^99mTc-pefloxacin is retained at the infectious site because of its specific binding to the gyrase enzymes of bacterial cells.     

Ligand exchange and solvolytic reactions of99mTcBr 6 2− in non-aqueous media

Prior work had documented that^99mTcCl ₆ ^2– could undergo ready ligand exchange reaction under non-aqueous condition. We now wish to report the ligand exchange reaction of bromine in^99mTcBr ₆ ^2– in non-aqueous solvents using 8-hydroxyquinoline (oxine) as the displacing ligand. Analysis of the products obtained by paper chromatography, HPLC and electrophoresis suggest that a 12 Tcoxine complex appears to be the most stable of the complexes formed, probably^99mTc(oxine)₂ Br₂. However, displacement of bromine by polar solvents (both protic and aprotic) can also occur, both on^99mTcBr ₆ ^2– and in the above complex as a consequence of solvolytic reactions. Other Tc-oxine complexes can also be formed upon ligand exchange, but they appear to be stable only under aprotic, non solvolytic conditions. These studies again document that hexahalotechnetate complexes exhibit ligand exchange reactions under non-aqueous conditions, that they allow the ready synthesis of novel technetium complexes, but that because of their high reactivity the effect of competing reactions must be considered.     

Synthesis,labeling and biodistribution of <Superscript>99m</Superscript>Tc-3-amino-2-quinoxalin-carbonitrile 1,4-dioxide in tumor bearing mice

3-Amino-2-quinoxalincarbonitrile 1,4-dioxide (AQCD) is a quinoxaline derivative, which was synthesized by condensation method. AQCD was labeled with ^99mTc with labeling yield above 90% investigated by paper chromatography. ^99mTc-AQCD was prepared using stannous chloride as reducing agent at pH 7 and 10 min reaction time. ^99mTc-AQCD should be freshly prepared, otherwise the yield significantly decreased after 15 min post labeling. Stability study of ^99mTc-AQCD reflected the short time stability of Biodistribution study of ^99 mTc-AQCD in tumor bearing mice reflected that its uptake in tumor sites in both ascites and solid tumor sites. This uptake of ^99mTc-AQCD in tumor sites was sufficient to radioimage the inoculated sites.     

Exchange labeling of proteins:99mTc labeled transferrin

^99mTc-labeled transferrin was prepared by reduction of^99mTcO ₄ ⁻ ; with stannous DTPA or stannous citrate followed by equilibration of the technetium chelate with human transferrin. The rate of transfer of^99mTc to transferrin in the presence of 0.015M citrate buffer was dependent on pH in the order pH 2.1> pH 7.2> pH 4.1> pH 5.9. The incorporation rate was inversely proportional to the concentration of DTPA and citrate buffer. The replacement of citrate buffer by acetate buffer or oxalate buffer reduced drastically the formation of^99mTc-labeled transferrin at pH 4.1. The formation of^99mTc-labeled transferrin prepared from the reduction of^99mTcO ₄ ⁻ with stannous citrate was faster than that from the reduction with stannous DTPA in the presence of 0.015M citrate buffer and pH 2.5. Equilibration of transferrin with^99mTc-labeled pyrophosphate did not produce^99mTc-labeled transferrin at pH 4.5. The ligand exchange labeling of^99mTc to transferrin in 0.015M citrate did not cause appreciable denaturation of the protein at all pH values. This method also enabled labeling of the protein in a low concentration (2.6·10⁻⁴ M) via tin reduction. Sequential external imaging of the^99mTc-labeled transferrin in Sprague-Dawley rats bearing Walker-256 carcinosarcoma showed optimal tumor localization occurred at 3 hr after injection. In spite of this,^99mTc-labeled transferrin does not appear to be a suitable imaging agent because of the low tumor to blood ratio of^99mTc (0.50±0.17) at 3 hr post injection. This is similar to that of^{6 7}Ga-citrate (0.43±0.15%).     

[99mTcN(PNP5)(NOEt)]+: A novel potential myocardial perfusion imaging agent

Summary The asymmetrical [^99mTcN(PNP5)(NOEt)]⁺heterocomplex containing a terminal technetium-nitrogen multiple bond coordinated to the diphosphine ligand (PNP5) and the dithiocarbamate ligand (NOEt), was prepared through ligand exchange reaction. Its radiochemical purity was over 90% as measured by TLC and HPLC. Biodistribution in mice and SPECT imaging in dog were studied. The results showed that [^99mTcN(PNP5)(NOEt)]⁺ possessed high myocardial uptake and good retention, and high target to non-target ratios, suggesting that it may be a potential myocardial perfusion imaging agent.     

Activation analysis for technetium-99 by the use of a neutron-excitation reaction

The formation of^99mTc was observed when⁹⁹Tc was irradiated by reactor neutrons as a result of the⁹⁹Tc(n, )^99mTc reaction. A good linearity was observed between the activities of^99mTc produced and⁹⁹Tc irradiated. The cross section of the excitation reaction was estimated to be 0.24 b. The application of the nuclear excitation reaction to the activation analysis for low level⁹⁹Tc was studied.     

Preparation and biological distribution of 99mTc-cefazolin complex, a novel agent for detecting sites of infection

The optimization of the radiolabeling yield of cefazolin with ^99mTc was described. Dependence of the labeling yield of ^99mTc-cefazolin complex on the amounts of cefazolin and SnCl₂·2H₂O, pH and reaction time was studied. Cefazolin was labeled with ^99mTc with a labeling yield of 89.5 % by using 1 mg cefazolin, 5 μg SnCl₂·2H₂O at pH 4 and 30 min reaction time. The radiochemical purity of ^99mTc-cefazolin was evaluated with ITLC. The formed ^99mTc-cefazolin complex was stable for a time up to 3 h, after that the labeling yield decreased 64.0 % at 8 h. Biological distribution of ^99mTc-cefazolin complex was investigated in experimentally induced inflammation mice, in the left thigh, using Staphylococcus aureus (bacterial infection model) and turpentine oil (sterile inflammation model). Both thighs of the mice were dissected and counted and the ratio of bacterial infected thigh/contralateral thigh was then evaluated. In case of bacterial infection, T/NT for ^99mTc-cefazolin complex was 8.57 ± 0.4 after 0.5 h, which was higher than that of the commercially available ^99mTc-ciprofloxacin under the same experimental conditions. The ability of ^99mTc-cefazolin to differentiate between septic and aseptic inflammation indicates that ^99mTc-cefazolin could undergo further clinical trials to be used for imaging sites of infection.     

Synthesis and biological distribution of 99mTc–norfloxacin complex, a novel agent for detecting sites of infection

The optimization of the radiolabeling yield of ciprofloxacin analogous, norfloxacin, with technetium-99m (^99mTc) was described. Dependence of the labeling yield of ^99mTc–norfloxacin complex on the concentration of norfloxacin, SnCl₂·2H₂O content, pH of the reaction mixture and reaction time was studied. Norfloxacin was labeled with ^99mTc at pH 3 with a labeling yield of 95.4% by using 5 mg norfloxacin, 50 μg SnCl₂·2H₂O and 30 min reaction time. The formed ^99mTc–norfloxacin complex was stable for a time up to 3 h. Biological distribution of ^99mTc–norfloxacin complex was investigated in experimentally induced inflammation rats using Staphylococcus aureus (bacterial infection model) and heat killed Staphylococcus aureus and turpentine oil (sterile inflammation model). In case of bacterial infection, the T/NT value for ^99mTc–norfloxacin complex was found to be 6.9 ± 0.4 which was higher than that of the commercially available ^99mTc–ciprofloxacin under the same experimental condition.     

Radioiodinated paroxetine, a novel potential radiopharmaceutical for lung perfusion scan

Paroxetine (a selective serotonin reuptake inhibitor) was successfully labeled with ¹²⁵I via direct electrophilic substitution reaction at ambient temperature. The reaction parameters studied were paroxetine amount, CAT amount, pH of the reaction mixture, reaction temperature, reaction time and in vitro stability of ¹²⁵I-paroxetine. ¹²⁵I-paroxetine was obtained with a maximum labeling yield of 94 ± 0.23% and in vitro stability up to 24 h. Biodistribution studies showed that maximum in vivo uptake of ¹²⁵I-paroxetine in lungs was 27.89 ± 1.03% injected activity/g tissue at 15 min post-injection and retention in lungs remained high up to 1 h, whereas the clearance from mice appeared to proceed mainly via the hepatobiliary pathway. ¹²⁵I-paroxetine is not a blood product and so it is more safe than the currently available ^99mTc-macroaggregated albumin (^99mTc-MAA), and its lung uptake is higher than that of the recently discovered ^99mTc(CO)₅I and ^99mTc-DHPM. As a conclusion, radioiodinated paroxetine could be used as a novel radiopharmaceutical for lung perfusion scan safer than the currently available ^99mTc-MAA and more potential than the recently discovered ^99mTc(CO)₅I and ^99mTc-DHPM.     

The interaction of <Superscript>99m</Superscript>Tc with pyrimidine compounds

The reaction of ^99mTc of different oxidation states (+7, +4) with 2-thiouracil and 5-nitrobarbituric acid have been studied at different temperatures, pH and concentrations. The reaction mixtures have been analyzed at different times using thin layer chromatography (TLC) and a radio detector to show the peaks at the plates. ^99mTc is obtained from the Mo generators with oxidation state (+7). The use of SnCl₂ as a reducing agent gave ^99mTc with oxidation state (+4). It is very difficult to separate the complexes formed from the reactions in very small concentration. The percentage of ^99mTc and its oxidation state involved in the complexes can be determined. The labeling efficiencies (percentage of complex) in the reaction of ^99mTc⁺⁷ with 5-nitro-barbituric-acid increases mostly at pH  10. Both oxidation states of ^99mTc(+7, +4) can be detected at pH’s 4 and 10, but at pH  4, the reduced form ^99mTCO₂, is more pronounced. At pH  7 no complexes were detected and most of ^99mTc remains as ^99mTCO₄ ⁻ . By increasing the ligand concentration, the labeling efficiencies of the complex increases. For the reaction of ^99mTc of oxidation states (+4, +7) with 2-thiouracil at different temperatures and analytical times it is concluded that several complexes with different R_f values were observed in equilibrium and most of these complexes were unstable.     

The preparation of99mTc-labelled methionine

^99mTc-labelled methionine was prepared by ligand substitution reaction. Methionine was reacted with^99mTc-citrate under physiological conditions, to form a radiochemically pure, neutral Tc complex. Labelling parameters involving incubation period of methionine in^99mTc-citrate solution were studied by paper and thin-layer chromatography.     

Synthesis and preclinical pharmacological evaluation of a novel 99mTc–shikonin as a potential tumor imaging agent

Shikonin was isolated from Ratanjot pigment then the obtained shikonin was well characterized. This study is aimed to optimize radiolabeling yield of shikonin with ^99mTc with respect to factors that affect the reaction conditions such as shikonin amount, SnCl₂·2H₂O amount, reaction time and pH of the reaction mixture. In vitro stability of the radiolabeled complex was checked and it was found to be stable for up to 6?h. Biodistribution studies showed that, ^99mTc?Cshikonin accumulate in tumor sites with higher T/NT than other currently available ^99mTc(CO)₃-VIP, ^99mTc?Cnitroimidazole analogues and ^99mTc?Cpolyamine analogues indicating that shikonin deliver ^99mTc to the tumor sites with a percentage sufficient for imaging and can overcome many drawbacks of other radiopharmaceuticals used for tumor imaging.     

Recovery of plutonium from nitric acid containing oxalate and fluoride by a macroporous bifunctional phosphinic acid resin (MPBPA)

Summary Piroxicam was labeled effectively with ^99mTc due to the presence of electron donating atoms such as sulfur, nitrogen, and oxygen in its structure. The labeling yield was found to be influenced by different factors such as the amount of piroxicam, stannous chloride dihydrate, pH of the reaction mixture, reaction time and reaction temperature. The suitable amount of stannous chloride dihydrate required to produce high labeling yield of ^99mTc-piroxicam was 50 μg, above this quantity (200 μg) a colloidal solution was formed. Another factor which plays a significant role in this labeling reaction is the pH of the reaction medium. The labeling reaction was done only at alkaline pH range from 9-11, because piroxicam was not soluble at acidic or neutral pH. The labeling reaction proceeded well at room temperature and the complex was decomposed by heat. The labeled piroxicam (^99mTc-piroxicam ) showed good localization in inflamed foci and good imaging must be taken at 24-hour post injection, as the ratio of both types of inflammation (sterile and septic) to the background are 10.6 and 8.7, respectively.