Neutron resonance capture analysis and applications

This paper addresses the development of two new radiopharmaceuticals for infection imaging. The optimization of the labeling yield of ciprofloxacin analogous, lomefloxacin and ofloxacin, with ^99mTc is described. ^99mTc-lomefloxacin was obtained with a radiochemical yield of 93.6% by adding ^99mTc to 2.5 mg lomefloxacin in the presence of 50 μg SnCl₂ while ^99mTc-ofloxacin was obtained (96.6%) by adding ^99mTc to 2 mg ofloxacin in the presence of 50 μg SnCl₂. Biodistribution studies in rats were carried out in experimentally induced infection in the left thigh using Staphylococcus aureus. Both thighs of the rats were dissected and counted and the ratio of bacterial infected thigh/contralateral thigh was then evaluated. ^99mTc-lomefloxacin showed higher uptake (T/NT = 6.5±0.5) in the infectious lesion than ^99mTc-ofloxacin (T/NT = 4.3±0.6) and abscess-to-muscle ratios for both preparations were higher than that of ^99mTc-ciprofloxacin (T/NT = 3.8±0.8), indicating that ^99mTc-lomefloxacin could be used for infection imaging.     

Quality control of a detector for the calculations of radiopharmacokinetic parameters of 99mTc-glucarate in rats

Good manufacturing practices specify that a well-type scintillation NaI(Tl) crystal detector has to be validated in order to detect radioactivity from any radiopharmaceutical used to obtain radiopharmacokinetic parameters. A 5 cm well-type NaI(Tl) scintillation detector was coupled to a multi-channel analyzer centered at the 140 keV ^99mTc peak with a 20% window. The area represents counts per minute (cpm). All the net cpm were decay corrected. The activity source was ^99mTc-glucarate developed as an imaging agent for acute myocardial infarction. Wistar rats were injected in a tail vein with 0.1 ml (3.7 MBq) of ^99mTc-glucarate solution and 13 blood samples were taken. The cpm were the input data for the WINNONLN program which calculates radiopharmacokinetic parameters. The detector's efficiency for ^99mTc was 15.03% and the sensitivity 1.12 kBq/ml in plasma. The response was linear between 0.31-14.3 kBq/ml of ^99mTc-glucarate. The maximum assay variation coefficient was 2.79 and recovery of ^99mTc-glucarate in plasma was 99.8%±0.2%. LOD was 0.31 kBq and LOQ = 1.12 kBq in plasma samples. ^99mTc-glucarate follows a two-compartment model of distribution with Vd of 21.74 ml±2.71 ml; a Vdss of 74.36 ml±12.67 ml; t _{1/2 a}0.74 h±0.19 h; t _{1/2 b} 18.98 h±4.36 h; AUC = 32.75 mCi/min^.ml ± 3.73 mCi/min^.ml; MRT = 24.35 h±5.51 h and total clearance 3.05 ml/h±0.35 ml/h. The well-type detector fulfills the quality system requirements and the radiopharmacokinetic parameters for ^99mTc-glucarate in rats are reliable. This revised version was published online in July 2006 with corrections to the Cover Date.     

Characterization of 99mTc(CO)3-iminodiacetic acid (IDA) and its comparison with 99mTc-(IDA)2 using compounds for hepatobiliary scintigraphy

The organometallic precursor of fac-[^99mTc(CO)₃(H₂O)₃]⁺ has attracted much attention because of the robustness and small size of Tc(I)-tricarbonyl complexes compared to Tc(V) complexes and the good labeling affinity with a variety of donor atoms. Among various ligand systems, an iminodiacetic acid (IDA) was proven as a good chelating group to form a Tc(III)-compelx as well as has been shown its potential as a chelating system for fac-[^99mTc(CO)₃] precursor. In an attempt to confirm the similarity and the difference between ^99mTc(CO)₃-IDA and ^99mTc-(IDA)₂-complex, M(CO)₃-IDA (M = ^99mTc, Re) complexes of disofenin, mebrofenin and N-(3-iodo-2,4,6-trimethyl phenylcarbamoylmethyl) iminodiacetic acid were prepared, and the biological evaluation of ^99mTc(CO)₃-disofenin was performed. The ^99mTc(CO)₃-IDA complexes were prepared with a high radiolabeling yield (>98%) in a quantitative manner and showed a negative charge. The in vivo pharmacokinetic behavior of ^99mTc(CO)₃-disofenin showed a similar biological activity to ^99mTc-(disofenin)₂ in that those complexes were quickly cleared from the blood by the hepatocytes and excreted into the gallbladder and intestine. Accordingly, the ^99mTc(CO)₃-IDA derivatives of disofenin and mebrofenin might be used as hepatobiliary imaging agents. Since an IDA is a promising chelator for ^99mTc-based radiopharmaceutical and the biological properties of ^99mTc(CO)₃-IDA derivative shows similar to that of ^99mTc-complex, a biomolecule containing IDA can be freely radiolabeled with fac-[^99mTc(CO)₃]-precursor or ^99mTc. However, the radiolabeling efficiency and the biological behavior demonstrates the favorable properties of ^99mTc(CO)₃-IDA compound for the development of a new imaging agent.     

Technetium-99m labeling of hippuric and p-amino-hippuric acid in the presence of DTPA: Biological and pharmacokinetic evaluation and comparison with99mTc-DTPA

^99mTc-Hipp as a modified^99mTc-DTPA, and^99mTc-PAH as a new renal agent are developed. Each veal of lyophilised kit contain hippuric (Hipp) or p-aminohippuric acid (PAH), diethyltriaminepentaacetic acid as calciumtrisodium salt (CaNa₃DTPA) and stannouschloride (SnCl₂·xH₂O), in molar ratio Hipp/PAH:DTPA=4∶1. They are high radiochemical purity radiopharmaceuticals, with hydrophilic character and low percentage of protein binding. The ITL chromatography and HPLC analyses of these labeled compounds have shown almost identical results as^99mTc-DTPA, but their biological behavior in rats confirm certain differences.^99mTc-Hipp is a renal agent clearing by the glomerular system, with better pharmacokinetical parameters than^99mTc-DTPA:t _1/2(α)=4.1 min,t _1/2(β)=198.6 min,K _cl=1.2·10⁻²min⁻¹ and a twofold value for blood clearance (Cl=2.07 ml/min).^99mTc-PAH is a quite different renal agent, rapidly secreted by kidney as a tubular secretion agent. Its pharmacokinetical parameters:t _1/2(α)=2.5 min,t _1/2(β)=41.7 min andK _cl=5.1·10⁻⁴ min⁻¹ are almost equal to those of^99mTc-MAG₃, but the blood clearance of Cl=5.22 ml/min is even higher than that of IOH clearance.     

Synthesis, biodistribution and evaluation of 99mTc-sitafloxacin kit: a novel infection imaging agent

Radiosynthesis of ^99mTc-sitafloxacin (^99mTc-STF) complex and its efficacy as a potential infection imaging agent was evaluated. Effect of sitafloxacin (STF) concentration, sodium pertechnetate (Na^99mTcO₄), stannous chloride dihydrate (SnCl₂·2H₂O), and pH on the % radiochemical purity yield (RCP) of ^99mTc-STF complex was studied. A stable ^99mTc-STF complex up to 120 min with maximum %RCP yield was observed by mixing 2 mg of STF with 3 mCi of Na^99mTcO₄ and 150 μL of SnCl₂·2H₂O (1 μg/μL in 0.01 N HCl) at a pH 5.5. Artificially infected rats with Staphylococcus aureus were used for studying the biodistribution behavior of the ^99mTc-STF complex. After 30 min of the intravenous (I.V.) administration of the ^99mTc-STF complex, 7.50 ± 0.10% was absorbed in the infected thigh of the rats and the uptake gradually increased to 18.50 ± 0.20% within 90 min. Rabbits with artificially induced infection were used for evaluating the scintigraphic accuracy. Higher uptake in the infected thigh was observed after 2 h of I.V. administration of the ^99mTc-STF complex. Target to non-target organ ratio of the % absorbed dose incase of infected/normal muscle was 6.82 ± 0.40, 17.11 ± 0.60, and 23.13 ± 1.00% at 30, 60 and 90 min of administration. Stable and higher %RCP, higher uptake in the infected thigh, and spectral studies, recommend the ^99mTc-STF for routine infection imaging.     

Study on the preparation and biological evaluation of <Superscript>99m</Superscript>Tc–gatifloxacin and <Superscript>99m</Superscript>Tc–cefepime complexes

The aim of this work is the development of new radiopharmaceuticals for imaging infection and inflammation in human. Gatifloxacin (fluoroquinolone derivative) and cefepime (cephalosporine derivative) are antibiotics used to treat bacterial infections were investigated to label with one of the most important radioactive isotopes (technetium-99m). The reaction parameters that affect the labeling yield such as substrate concentration, stannous chloride dihydrate concentration, pH of the reaction mixture, and reaction time were studied to optimize the labeling conditions. Maximum radiochemical yield of ^99mTc–gatifloxacin (90  ± 1.8%) complex was obtained by using 50 μg SnCl₂·2H₂O and 2.5 mg gatifloxacin at pH 10 while ^99mTc–cefepime was prepared at pH 8 with a maximum radiochemical yield of 98  ± 1.4% by adding ^99mTc to 5 mg cefepime in the presence of 50 μg SnCl₂·2H₂O. Biological distribution of ^99mTc–gatifloxacin and ^99mTc–cefepime was carried out in experimentally induced infection rats, in the left thigh, using Escherichia coli. Both thighs of the rats were dissected and counted and the ratio of bacterial infected thigh/contralateral thigh was then evaluated. T/NT for both ^99mTc–gatifloxacin and ^99mTc–cefepime was found to be 4.5  ± 0.3 and 8.4  ± 0.1, respectively, which was higher than that of the commercially available ^99mTc–ciprofloxacin. The abscess to normal muscle ratio indicated that ^99mTc–cefepime could be used for infection imaging. Besides, in vitro studies showed that ^99mTc–cefepime can differentiate between bacterial infection and sterile inflammation.     

99mTc-DMSA complex preparation: the effect of pH and tin(II) chloride amount on reaction

Labelling of meso-2,3-dimercaptosuccinic acid (DMSA) with technetium-99m was reinvestigated. Dependence of the ^99mTc-DMSA complex formation on the molar ratio of DMSA:reducing agent (SnCl₂·2H₂O) and pH was studied. Five different types of ^99mTc-DMSA complexes were determined. Especially three different complexes were established in the clinically used and prepared DMSA kit labelled with ^99mTc under alkaline condition. This radiopharmaceutical is used as imaging agent of the primary medullary carcinoma in the thyroid gland and different metastasis types. The existence of all complexes was observed by paper chromatography, paper electrophoresis and high performance liquid chromatography.     

Synthesis and biodistribution of 99mTc(CO)3-DMSA-MIBI in mice

Mixed ligand fac-tricarbonyl complex of [^99mTc(CO)₃-DMSA-MIBI] has been prepared starting from the precursor [^99mTc(OH₂)₃(CO)₃]⁺. The complex can be obtained in good yield and purity in a two-step procedure by first attaching meso-2,3-dimercaptosuccinic acid (DMSA, HOOCCH(SH)CH(SH)COOH) with [^99mTc(OH₂)₃(CO)₃]⁺, followed by addition of MIBI [tetrakis-2-methoxyisobutylisonitrile (CH₃OC(CH₃)₂CH₂-N≡C) copper(I) tetrafluoroborate] solution. The complex was characterized by TLC and HPLC and was studied by means of octanol-water partition coefficient, electrophoresis, stability in vitro, and normal mice experiment. Biodistribution in mice demonstrated that the complex showed higher myocardial uptake after 0.5-hour p.i. The ratios of heart/liver (%ID/g) in the case of ^99mTc(CO)₃-DMSA-MIBI was higher (1.88) than that observed in case of ^99mTc-MIBI¹ (0.93) after 0.5-hour p.i. (P<0.05). Results showed that the complex may be developed to a novel myocardial perfusion-imaging agent.     

Evaluation and comparison of 99mTc-labeled d-glucosamine derivatives with different 99mTc cores as potential tumor imaging agents

Isocyanide is a strong coordination ligand that can coordinate with [^99mTc(I)(CO)₃]⁺ core and [^99mTc(I)]⁺ core to produce stable ^99mTc complexes, therefore developing a ^99mTc-labeled isocyanide complex for single-photon emission computed tomography (SPECT) imaging is considered to be of great interest. In order to develop potential tumor imaging agents with satisfied tumor uptake and suitable pharmacokinetic properties in vivo, a novel d -glucosamine isocyanide derivative, 4-isocyano-N-(2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)butanamide (CN3DG), was synthesized and radiolabeled with [^99mTc(I)]⁺ and [^99mTc(CO)₃]⁺ cores to obtain [^99mTc(CN3DG)₆]⁺ and [^99mTc(CO)₃(CN3DG)₃]⁺ in high radiolabeling yields (>95%). Both of the complexes showed good hydrophilicity and great stability in vitro. Cell uptake studies performed in S180 cells demonstrated they were transported into cells by glucose transporters. Biodistribution studies of the two complexes in mice bearing S180 tumor showed they had high tumor uptakes and rapid clearance from muscle and blood so that the tumor/blood and tumor/muscle ratios were high. By comparison, [^99mTc(CN3DG)₆]⁺ was superior to [^99mTc(CO)₃(CN3DG)₃]⁺ in regard to tumor uptake, tumor/blood and tumor/liver ratios. S180 tumors could be seen clearly from the SPECT/CT images with [^99mTc(CN3DG)₆]⁺. Considering its favorable properties, [^99mTc(CN3DG)₆]⁺ would be a promising tumor imaging agent and needs to be further studied.     

Novel 99mTc labeled σ receptor ligand as a potential tumor imaging agent

A novel ^99mTc labeled complex, [N-[2-((2-oxo-2-(4-(3-phenylpropyl)piperazin-1-yl)ethyl) (2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato]Technetium(V) oxide (PPPE-MAMA’-^99mTcO) ([ ^99m Tc]-2) has been designed and prepared based on the integrated approach. The corresponding rhenium complex (PPPE-MAMA’-ReO)(Re-2) has been prepared and characterized. In vitro competition binding assays show moderate affinity of Re-2 towards σ₁ and σ₂ receptors with K _i values of 8.67 ± 0.07 and 5.71 ± 1.88 μmol, respectively. Planar images obtained at 0.5 h, 4 h, 20 h after i.v. injection indicate the accumulation of [ ^99m Tc]-2 in MCF-7 human breast tumor bearing mice at 20 h. Furthermore, the accumulation of [ ^99m Tc]-2 has been inhibited at 20 h after co-injection of [ ^99m Tc]-2 plus haloperidol (1 mg/kg). Biodistribution studies of [ ^99m Tc]-2 display an in vivo tumor uptake of 0.14% ± 0.01% ID/g at 24 h post i.v. injection with a tumor/muscle ratio of 6.02 ± 0.87. The above results suggest that [ ^99m Tc]-2, derived from a previously published lead compound, retains certain tumor uptake and affinity for σ receptors. [ ^99m Tc]-2 may be used as a basis for further structural modifications to develop tumor imaging agents with high affinity for σ receptors.     

Synthesis and preliminary biological evaluation of a technetium-99m labeled thymidine analog

The synthesis and labeling of ^99mTc-N³-（N’-[2-sulfanyl-ethylamino）acetyl]-2-aminoethyl-sulfanyl-1-hexanamide}thymidine (^99mTc-NHT) were studied.In the presence of sodium glucoheptonate（GH） and ethylene diamine tetraacetic acid（EDTA）,^99mTc-NHT was obtained by using bisaminoethanethiol（N₂S₂） as a bifunctional coupling agent.The radiochemical purity of the ^99mTc-NHT was over 95%.Biodistribution of ^99mTc-NHT was performed in hepatoma HepA tumor-bearing mice.At 2 h p.i.,the ratios of tumor-to-muscle,tumor-to-bone and tumor-to-blood were 4.41±0.32,2.45±0.24 and 1.51±0.18,respectively.     

Labeling and biodistribution of 99mTc-7-bromo-1,4-dihydro-4-oxo-quinolin-3-carboxylic acid complex

7-Bromo-1,4-dihydro-4-oxo-quinolin-3-carboxylic acid (BDOQCA), was synthesized with a yield of 93% and well characterized. The obtained compound was investigated to label with one of the most important radioactive isotopes (technetium-99m). Effect of BDOQCA concentration, stannous chloride dihydrates (SnCl₂.2H₂O) concentration, pH and reaction time on the percent labeling yield of ^99mTc-BDOQCA complex was studied in details. ^99mTc-BDOQCA complex was obtained at a maximum yield of 97.3% by mixing 2.5 mg of BDOQCA with 25 μg SnCl₂.2H₂O at pH 6 and 30 min reaction time and the formed complex was stable for a time up to 8 h with a maximum yield of 97.3%. Biodistribution studies in mice were carried out using experimentally induced infection in the left thigh using E. coli. Both thighs of the mice were dissected and counted to evaluate the ratio of bacterial infected thigh/contralateral thigh. Higher uptake in the infected thigh was observed after 2 h of IV administration of ^99mTc-BDOQCA complex (T/NT = 7.6 ± 0.6%) than that of the commercially available ^99mTc-ciprofloxacin complex (T/NT = 3.8 ± 1%). The in vitro binding and biodistribution of ^99mTc-BDOQCA complex in the septic and aseptic inflammation bearing mice showed that, ^99mTc-BDOQCA complex is a promising agent for infection imaging and can differentiate between infected and inflamed muscle.     

<Superscript>99m</Superscript>Tc(CO)<Subscript>3</Subscript>–AOPA colchicine conjugate as a potential tumor imaging agent

This work reports the synthesis, radiolabeling and preliminary biodistribution results in tumor-bearing mice of the ^99mTc(CO)₃–AOPA colchicine conjugate. The novel ligand was successfully synthesized by conjugation of N-(acetyloxy)-2-picolylamino (AOPA) to deacetylcolchicine via a short carbonyl-methylene linker. Radiolabeling was performed in high yield with [^99mTc(CO)₃]⁺ core. ^99mTc(CO)₃–AOPA colchicine conjugate was hydrophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that ^99mTc(CO)₃–AOPA colchicine conjugate accumulated in the tumor with good uptake and retention. However, its clearance from normal organs was not so fast, resulting in poor T/NT ratios. Further modification on the linker or/and ^99mTc-chelate to improve the tumor targeting efficacy and in vivo kinetic profiles is currently in progress.     

Synthesis,radiochemical and biological characteristics of <Superscript>99m</Superscript>Tc-8-hydroxy-7-substituted quinoline complex: a novel agent for infection imaging

2,2′-[(8-hydroxyquinolin-7-yl)methylazanediyl]diacetic acid (HQMADA) was synthesized via reaction of 8-hydroxyquinoline with iminodiacetic acid in presence of paraformaldehyde with a yield of 27%. The obtained compound was well characterized via different analytical techniques. Labeling of the synthesized compound with technetium-99m in pertechnetate form (^99mTcO₄ ⁻) in the presence of stannous chloride dihydrate was carried out via chelation reaction. The reaction parameters that affect the labeling yield such as HQMADA concentration, stannous chloride dihydrate concentration, pH of the reaction mixture, and reaction time were studied to optimize the labeling conditions. Maximum radiochemical yield of ^99mTc-HQMADA complex (91.9%) was obtained by using 1.5 mg HQMADA, 50 μg SnCl₂·2H₂O, pH 8 and 30 min reaction time. Biodistribution studies in mice were carried out in experimentally induced infection in the left thigh using E. coli. ^99mTc-HQMADA complex showed higher uptake (T/NT = 5.5 ± 0.3) in the infectious lesion than the commercially available ^99mTc-ciprofloxacin (T/NT = 3.8 ± 0.8). Biodistribution studies for ^99mTc-HQMADA complex in Albino mice bearing septic and aseptic inflammation models showed that ^99mTc-HQMADA complex able to differentiate between septic and aseptic inflammation.     

A new agent for sentinel lymph node detection: preliminary results

Sentinel lymph node detection is widely used to identify lymph nodes that receive lymphatic drainage from a primary tumor. ^99mTc labeled iron oxide nanoparticles were prepared to invent a new colorful radioactive agent for sentinel lymph node detection. Iron oxide nanoparticles were produced by co-precipitation of FeCl₃ and FeCl₂ in the presence of NaOH. Then iron oxide nanoparticles were labeled with ^99mTc. ^99mTc labeled nanoparticles (7.4 MBq/0.1 mL) were intradermally injected in the distal hind limb of 16 rabbits. Dynamic and static lymphoscintigraphic images were taken for 24 h. Labeling efficiencies of ^99mTc-iron oxide nanoparticles were over 99%. Their sizes are between 50 and 60 nm. ^99mTc-iron oxide nanoparticles were accumulated in the popliteal lymph node in 11 of 16 rabbits (69%). Retention of nanoparticles in the popliteal lymph node was obvious at from 2nd through 24th hours. The radioactive lymph node was identified easily by gamma probe. The popliteal lymph node was excised and established for radioactivity and black dye. These black and radioactive nanoparticles may be potential agent successfully used for sentinel lymph node detection.     

Preparation of <Superscript>99m</Superscript>Tc-PQQ and preliminary biological evaluation for the NMDA receptor

Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator and nerve growth factor found in a class of enzymes called quinoproteins, was labeled with ^99mTc by using stannous fluoride (SnF₂) method. Radiolabeling qualification, quality control and characterization of ^99mTc-PQQ and its biodistribution studies in mice were performed and discussed. Effects of pH values, temperature, time and reducing agents concentration on the radiolabeling yield were investigated. The quality control procedure of ^99mTc-PQQ was determined by thin layer chromatography (TLC), radio high-performance liquid chromatography (RHPLC) and paper electrophoresis methods. The average radiolabeling yield was 94 ± 1% under optimum conditions of 0.99 mg of PQQ, 30 μg of SnF₂, 0.5 mg of ethylenediaminetetraacetic acid disodium salt (EDTA-2Na) and 18.5 MBq of Na^99mTcO₄ at pH 6 and 25 °C with a response volume of 1 ± 0.1 mL. ^99mTc-PQQ was stable and anionic. Lipid–water partition coefficient of ^99mTc-PQQ was −1.49 ± 0.16. The pharmacokinetics parameters of ^99mTc-PQQ were t _1/2α = 18.16 min, t _1/2β = 100.45 min, K ₁₂ = 0.013 min⁻¹, K ₂₁ = 0.017 min⁻¹, K _e = 0.016 min⁻¹, AUC (area under the curve) = 1040.78 ID% g⁻¹ min and CL (plasma clearance) = 0.096 mL min⁻¹. The dual-exponential equation was Y = 10.88e^−0.038t  + 5.21e^−0.0069t . The biodistribution of ^99mTc-PQQ was studied in ICR (Institute for Cancer Research 7701 Burhelme Are., Fox Chase, Philadelphia, PA 1911 USA) mice. In vitro autoradiographic studies clearly showed that the ^99mTc-PQQ radioactivity accumulated predominantly in the hippocampus and cortex, which had a high density of N-methyl-d-aspartate Receptor (NMDAR). The enrichment can be blocked by NMDAR redox modulatory site antagonists-ebselen (EB) and ^99mTc-PQQ is therefore a promising candidate for the molecular imaging of NMDAR. To date, however, there have been no studies characterizing ^99mTc-PQQ.     

Synthesis and biological evaluation of novel 99mTc‐oxo and 99mTc‐tricarbonyl complexes with C3′‐functionalized thymidine dithiocarbamate for tumor imaging

A novel C3′‐functionalized thymidine dithiocarbamate derivative (3’DTC‐TdR) was successfully synthesized and labelled using [^99mTcO]³⁺ core and [^99mTc(CO)₃(H₂O)₃]⁺ core with high yields. The structures of the ^99mTc complexes were verified by preparation and characterization of the corresponding stable rhenium complexes. Both of the complexes were lipophilic and stable in vitro. Cell internalization experiments indicated that the uptakes of ^99mTcO‐3’DTC‐TdR were related to nucleoside transporters. Biodistribution of these complexes in mice bearing tumor showed that they had high tumor uptakes, good tumor/muscle ratios and tumor/blood ratios. Especially for ^99mTcO‐3’DTC‐TdR, it exhibited the highest tumor/muscle ratio and tumor/blood ratio at 4 h post‐injection. SPECT/CT imaging studies indicated clear accumulation in tumor, suggesting ^99mTcO‐3’DTC‐TdR would be a promising candidate for tumor imaging.     

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.     

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.     

In vitro incorporation studies of 99mTc–alendronate sodium at different bone cell lines

Bisphosphonates can be labeled with Technetium-99m (^99mTc) and are used for bone imaging because of their good localization in the skeleton and rapid clearance from soft tissues. Over the last decades bone scintigraphy has been used extensively in the evaluation of oncological patients to provide information about the sites of bone lesions, their prognosis and the effectiveness of therapy by showing the sequential changes in tracer uptake. Since the lesion visualization and lesion/bone ratio are important utilities for a bone scanning radiopharmaceutic; in this study incorporation of ^99mTc labeled alendronate sodium (^99mTc–ALD) was evaluated in U₂OS (human bone osteosarcoma) and NCI-H209 (human bone carcinoma) cell lines. ALD was directly labeled by ^99mTc, radiochemical purity and stability of the complex were analyzed by radioactive thin layer chromatography and radioactive high performance liquid chromatography studies. For cell incorporation study, NCI-H209 and U₂OS cell lines were used with standard cell culture methods. The six well plates were used for all experiments and the integrity of each cell monolayer was checked by measuring its transepithelial electrical resistance (TEER) with an epithelial voltammeter. Results confirmed that ALD was successfully radiolabeled with ^99mTc. ^99mTc–ALD incorporated with NCI-H209 and U₂OS cells. The uptake percentages of ^99mTc–ALD in NCI-H209 and U₂OS cell lines were found significantly different. Since ^99mTc–ALD highly uptake in cancer cell line, the results demonstrated that radiolabeled ALD may be a promising agent for bone cancer diagnosis.