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.     

Preparation and Evaluation of Novel Folate Isonitrile 99mTc Complexes as Potential Tumor Imaging Agents to Target Folate Receptors

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA had specific tumor uptake. Compared with [^99mTc]Tc-CN5FA, the tumor/muscle ratios of [^99mTc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two ^99mTc complexes have potential as tumor imaging agents to target folate receptors.     

Radiosynthesis and evaluation of novel [99mTc(I)]+ and [99mTc(I)(CO)3]+ complexes with a 4-nitroimidazole isocyanide for imaging tumor hypoxia

[^99mTc(I)]⁺ and [^99mTc(I)(CO)₃]⁺ complexes with isocyanide exhibit high stability, which makes them suitable platforms to develop novel ^99mTc radiopharmaceuticals. To develop novel ^99mTc radiotracers for imaging hypoxia, in this study, a novel L ligand (4-nitroimidazole isocyanide derivative) was synthesized and labelled using [^99mTc(I)]⁺ core and [^99mTc(I)(CO)₃]⁺ core to produce [^99mTc(L)₆]⁺ and [^99mTc(CO)₃(L)₃]⁺ with high yields. To verify the structure of the ^99mTc complexes, corresponding rhenium analogues were synthesized and characterized. Both of the ^99mTc complexes were stable and hydrophilic. in vitro cellular uptake results showed they could exhibit good hypoxic selectivity. The evaluation of biodistribution in mice bearing S180 tumors indicated both of them could accumulate in tumor. Between them, [^99mTc(L)₆]⁺ exhibited higher tumor uptake and tumor/non-target ratio than [^99mTc(CO)₃(L)₃]⁺. Further, single photon emission computed tomography (SPECT) imaging studies of [^99mTc(L)₆]⁺ indicated an obvious accumulation in tumor and the value of the region-of-interest (ROI) ratio of the uptake for the tumor site to the corresponding non-tumor region was 5.64 ± 0.52. The above results suggested [^99mTc(L)₆]⁺ would be a potential tracer for imaging tumor hypoxia.     

Preparation and preliminary evaluation of a tris-metronidazole-<Superscript>99m</Superscript>Tc(CO)<Subscript>3</Subscript> complex for targeting tumor hypoxia

Conventional ^99mTc-radiopharmaceuticals for the detection of tumor hypoxia generally possess a single nitroimidazole moiety. Herein, we report the synthesis and evaluation of a ^99mTc-complex with three-nitroimidazole moieties in an attempt to improve hypoxic cell detection. Isocyanide derivative of metronidazole (MetroNC) was synthesized and subsequently radiolabeled with [^99mTc(CO)₃(H₂O)₃]⁺ precursor complex, wherein the three labile water molecules were replaced with MetroNC ligand to form a pseudo-octahedral [^99mTc(CO)₃(MetroNC)₃]⁺ complex. Analysis of corresponding Re(CO)₃-analog prepared in macroscopic scale confirmed the formation of expected complex. Cyclic voltammetric studies of [Re(CO)₃(MetroNC)₃]⁺ complex showed no significant change in single-electron reduction potential (SERP) of MetroNC ligand (??0.96 V) upon forming the [Re(CO)₃(MetroNC)₃]⁺ complex (??0.90 V). In vitro studies in Chinese hamster ovary (CHO) cells showed three-fold preferential accumulation of [^99mTc(CO)₃(MetroNC)₃]⁺ complex in hypoxic cells over normoxic cells. Biodistribution studies of [^99mTc(CO)₃(MetroNC)₃]⁺ complex in Swiss mice bearing fibrosarcoma tumor showed tumor uptake and steady retention till 60 min post injection. Present study constitutes a novel design approach towards development of a ^99mTc-radiopharmaceutical for hypoxia imaging application, which could be extended to other potential nitroimidazole ligands.     

Impact of Different [Tc(N)PNP]-Scaffolds on the Biological Properties of the Small cRGDfK Peptide: Synthesis,In Vitro and In Vivo Evaluations

Background: The [^99mTc][Tc(N)(PNP)] system, where PNP is a bisphosphinoamine, is an interesting platform for the development of tumor ‘receptor-specific’ agents. Here, we compared the reactivity and impact of three [Tc(N)(PNP)] frameworks on the stability, receptor targeting properties, biodistribution, and metabolism of the corresponding [^99mTc][Tc(N)(PNP)]-tagged cRGDfK peptide to determine the best performing agent and to select the framework useful for the preparation of [^99mTc][Tc(N)(PNP)]-housing molecular targeting agents. Methods: cRGDfK pentapeptide was conjugated to Cys and labeled with each [Tc(N)(PNP)] framework. Radioconjugates were assessed for their lipophilicity, stability, in vitro and in vivo targeting properties, and performance. Results: All compounds were equally synthetically accessible and easy to purify (RCY ≥ 95%). The main influences of the synthon on the targeting peptide were observed in in vitro cell binding and in vivo. Conclusions: The variation in the substituents on the phosphorus atoms of the PNP enables a fine tuning of the biological features of the radioconjugates. ws[^99mTc][Tc(N)(PNP3OH)]– and [^99mTc][Tc(N)(PNP3)]– are better performing synthons in terms of labeling efficiency and in vivo performance than the [^99mTc][Tc(N)(PNP43)] framework and are therefore more suitable for further radiopharmaceutical purposes. Furthermore, the good labeling properties of the ws[^99mTc][Tc(N)(PNP3OH)]– framework can be exploited to extend this technology to the labeling of temperature-sensitive biomolecules suitable for SPECT imaging.     

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [^99mTc]Tc-Sestamibi, [^99mTc]Tc-Tetrofosmin, and [^99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [^99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [^99mTc]Tc-Sestamibi and [^99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in ^99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies.     

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.     

A Review on the Current State and Future Perspectives of [99mTc]Tc-Housed PSMA-i in Prostate Cancer

Recently, prostate-specific membrane antigen (PSMA) has gained momentum in tumor nuclear molecular imaging as an excellent target for both the diagnosis and therapy of prostate cancer. Since 2008, after years of preclinical research efforts, a plentitude of radiolabeled compounds mainly based on low molecular weight PSMA inhibitors (PSMA-i) have been described for imaging and theranostic applications, and some of them have been transferred to the clinic. Most of these compounds include radiometals (e.g., ⁶⁸Ga, ⁶⁴Cu, ¹⁷⁷Lu) for positron emission tomography (PET) imaging or endoradiotherapy. Nowadays, although the development of new PET tracers has caused a significant drop in single-photon emission tomography (SPECT) research programs and the development of new technetium-99m (^99mTc) tracers is rare, this radionuclide remains the best atom for SPECT imaging owing to its ideal physical decay properties, convenient availability, and rich and versatile coordination chemistry. Indeed, ^99mTc still plays a relevant role in diagnostic nuclear medicine, as the number of clinical examinations based on ^99mTc outscores that of PET agents and ^99mTc-PSMA SPECT/CT may be a cost-effective alternative for ⁶⁸Ga-PSMA PET/CT. This review aims to give an overview of the specific features of the developed [^99mTc]Tc-tagged PSMA agents with particular attention to [^99mTc]Tc-PSMA-i. The chemical and pharmacological properties of the latter will be compared and discussed, highlighting the pros and cons with respect to [⁶⁸Ga]Ga-PSMA11.     

Synthesis and preliminary biological evaluation of 99mTc(CO)3-labeled pegylated 2-nitroimidazoles

This work reports the synthesis, radiolabeling and preliminary biodistribution results in tumor-bearing mice of ^99mTc(CO)₃-labeled pegylated (PEG) 2-nitroimidazoles for tumor hypoxia imaging. The novel 2-nitroimidazole derivatives were successfully synthesized by conjugation of tridendate chelators to 2-nitroimidazole via PEG₃ linker. Radiolabeling was performed in high yield with [^99mTc(CO)₃]⁺ core to get cationic [^99mTc(CO)₃(BPA-PEG₃-NIM)]⁺, neutral [^99mTc(CO)₃(AOPA-PEG₃-NIM)] and anionic [^99mTc(CO)₃(IDA-PEG₃-NIM)]^? respectively, all of which were hydrophilic and stable at room temperature. Biodistribution studies in tumor-bearing mice showed that ^99mTc(CO)₃-labeled pegylated 2-nitroimidazoles accumulated in the tumor with low uptake. ^99mTc-chelate and charge had significant impact on partition coefficient, radiotracer tumor uptake and pharmacokinetic properties. The results indicate the need for synthetic modification of the parent 2-nitroimidazole derivatives and the ^99mTc-chelate with a view to improve the tumor targeting efficacy and in vivo kinetic profiles.     

Preparation and Biological Evaluation of [99mTc]Tc-CNGU as a PSMA-Targeted Radiotracer for the Imaging of Prostate Cancer

Prostate-specific membrane antigen (PSMA) is a well-established biological target that is overexpressed on the surface of prostate cancer lesions. Radionuclide-labeled small-molecule PSMA inhibitors have been shown to be promising PSMA-specific agents for the diagnosis and therapy of prostate cancer. In this study, a glutamate-urea-based PSMA-targeted ligand containing an isonitrile (CNGU) was synthesized and labeled with ^99mTc to prepare [^99mTc]Tc-CNGU with a high radiochemical purity (RCP). The CNGU ligand showed a high affinity toward PSMA (K_i value is 8.79 nM) in LNCaP cells. The [^99mTc]Tc-CNGU exhibited a good stability in vitro and hydrophilicity (log P = −1.97 ± 0.03). In biodistribution studies, BALB/c nude mice bearing LNCaP xenografts showed that the complex had a high tumor uptake with 4.86 ± 1.19% ID/g, which decreased to 1.74 ± 0.90% ID/g after a pre-injection of the selective PSMA inhibitor ZJ-43, suggesting that it was a PSMA-specific agent. Micro-SPECT imaging demonstrated that the [^99mTc]Tc-CNGU had a tumor uptake and that the uptake was reduced in the image after blocking with ZJ-43, further confirming its PSMA specificity. All of the results in this work indicated that [^99mTc]Tc-CNGU is a promising PSMA-specific tracer for the imaging of prostate cancer.     

Bioevaluation of 99mTc(CO)3–Guanine in vitro and in vivo

The aim of this study is to examine biological behaviour of radiolabeled guanine with [Tc(CO)₃]⁺ core in vitro and in vivo. In vitro biological behavior of ^99mTc(CO)₃–Gua was evaluated on Lung (A-549), Breast (MCF-7), Colonic (Caco) carcinoma cell lines and normal human bronchial epithelial (NHBE). ^99mTc(CO)₃–Gua compound showed high uptake on A-549 cell line when compared to NHBE cell line. Biodistribution characteristics of ^99mTc(CO)₃–Gua was evaluated using New Zeland Rabbits. Scintigraphic results showed that a high level of radioactivity was observed in the lungs and liver shortly after administration of the ^99mTc(CO)₃–Gua and excretion takes place via both renal and hepatobiliary route. It was concluded that ^99mTc(CO)₃–Gua could be used as a nucleotide radiopharmaceutical for imaging purposes.     

Tetraamine‐Derived Bifunctional Chelators for Technetium‐99m Labelling: Synthesis,Bioconjugation and Evaluation as Targeted SPECT Imaging Probes for GRP‐Receptor‐Positive Tumours

Owing to its optimal nuclear properties, ready availability, low cost and favourable dosimetry, ^99mTc continues to be the ideal radioisotope for medical‐imaging applications. Bifunctional chelators based on a tetraamine framework exhibit facile complexation with Tc(V)O₂ to form monocationic species with high in vivo stability and significant hydrophilicity, which leads to favourable pharmacokinetics. The synthesis of a series of 1,4,8,11‐tetraazaundecane derivatives ( 01 – 06 ) containing different functional groups at the 6‐position for the conjugation of biomolecules and subsequent labelling with ^99mTc is described herein. The chelator 01 was used as a starting material for the facile synthesis of chelators functionalised with OH ( 02 ), N₃ ( 04 ) and O‐succinyl ester ( 05 ) groups. A straightforward and easy synthesis of carboxyl‐functionalised tetraamine‐based chelator 06 was achieved by using inexpensive and commercially available starting materials. Conjugation of 06 to a potent bombesin‐antagonist peptide and subsequent labelling with ^99mTc afforded the radiotracer ^99mTc‐N4‐BB‐ANT, with radiolabelling yields of >97 % at a specific activity of 37 GBq μmol^?1. An IC₅₀ value of (3.7±1.3) nM was obtained, which confirmed the high affinity of the conjugate to the gastrin‐releasing‐peptide receptor (GRPr). Immunofluorescence and calcium mobilisation assays confirmed the strong antagonist properties of the conjugate. In vivo pharmacokinetic studies of ^99mTc‐N4‐BB‐ANT showed high and specific uptake in PC3 xenografts and in other GRPr‐positive organs. The tumour uptake was (22.5±2.6) % injected activity per gram (% IA g^?1) at 1 h post injection (p.i.). and increased to (29.9±4.0) % IA g^?1 at 4 h p.i. The SPECT/computed tomography (CT) images showed high tumour uptake, clear background and negligible radioactivity in the abdomen. The promising preclinical results of ^99mTc‐N4‐BB‐ANT warrant its potential candidature for clinical translation.     

Radiocharacterization of the 99mTc�Crufloxacin complex and biological evaluation in Staphylococcus aureus infected rat model

^99mTc?Crufloxacin (^99mTc?CRUN) complex was prepared by reaction of different amounts of reduced sodium pertechnetate with different amount of Rufloxacin (RUN) antibiotic for the in vivo scintigraphic localization of the Staphylococcus aureus (S. aureus) infectious foci in Male Wister Rats (MWR) model. The ^99mTc?CRUN complex was radiochemically and biologically characterized in terms of radiochemical stability in saline, serum, in vitro binding with S. aureus and biodistribution in artificially infected with S. aureus MWR. The ^99mTc?CRUN complex showed stability more than 90% up to 240 min in normal saline with a maximum stability value of 98.10 ± 0.18% at 30 min after reconstitution. At 37 °C the complex showed in vitro permanence in serum up to 16 h with 13.90% side products during incubation. The ^99mTc?CRUN complex showed saturated in vitro binding with S. aureus at different intervals with a maximum uptake value of 71.50%. Infected to normal muscle, infected to inflamed and inflamed to normal muscles ratios were approximately 6.04, 4.31 and 1.40. Based on the stability of the complex in saline, serum, in vitro binding with S. aureus and biodistribution results, the ^99mTc?CRUN complex is recommended for in vivo scintigraphic localization of the S. aureus in vivo infectious foci in human.     

The stability of99mTc phosphorus compounds in plasma both in vivo and in vitro

The in vivo and in vitro stability of^99mTc hydroxyethlylidene diphosphonate, 99^mTc methylenediphosphonate and^99mTc pyrophosphate in plasma has been studied using paper chromatographic technique as the analytical tool. The results indicate that the amounts of^99mTc activity found both at the origin and R_f range of^99mTcO₄ ^? for in vivo experiments are slightly greater than those for either in vitro or control experiments. However, this amount of^99mTc activity represents about 0.16–0.4% of the injected dose. Therefore, it is suggested that^99mTc phosphorus radiopharmaceuticals are stable in vivo and neither oxidation nor hydrolysis of these bone imaging agents occurs in the blood.     

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.     

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.     

Preparation and biological evaluation of Tc-CO-MIBI as myocardial perfusion imaging agent

^99mTc-Sestamibi has been playing an important role in the cardiac imaging for the last decades. Previously, we reported that [^99mTc(CO)₃(MIBI)₃]⁺ demonstrated a significant location in myocardium with a lower liver uptake as compared with ^99mTc-Sestamibi. In this work, we found that new [^99mTc(CO)₂(MIBI)₄]⁺ could be prepared with high radiochemical purity. The inter-transformations between [^99mTc(CO)₃(H₂O)(MIBI)₂]⁺, [^99mTc(CO)₃(MIBI)₃]⁺, and [^99mTc(CO)₂(MIBI)₄]⁺ were investigated and biodistribution was performed to evaluate the [^99mTc(CO)₂(MIBI)₄]⁺ as a myocardial perfusion imaging agent. The results showed that one more CO was replaced by MIBI slowing down the pharmacokinetics. The structure characterization was performed on their corresponding rhenium complexes, and the results indicated that there were differences between ^99mTc-CO-MIBI and Re-CO-MIBI in preparation and hydrophobic characteristics.     

Sol–gel synthesis of a humic acid-silica gel composite material as low-cost adsorbent for thorium and uranium removal

In the present work, three neutral ^99mTc(CO)₃ complexes of nitroimidazole were synthesized and their potential to detect tumor hypoxia is evaluated in vivo. Triazole derivatives of 2-, 4- and 5-nitroimidazole were synthesized via ‘click chemistry’ route. The ligands synthesized were characterized and subsequently radiolabeled using [^99mTc(CO)₃(H₂O)₃]⁺ precursor complex to obtain corresponding neutral ^99mTc(CO)₃ complexes in >90 % radio chemical purity. The complexes were subsequently evaluated in Swiss mice bearing fibrosarcoma tumor and in vivo distribution observed was thoroughly analyzed. All complexes showed uptake in tumor, however, contrary to general expectations, the 5-nitroimidazole complex showed significantly higher tumor uptake (p < 0.05) at 30 min and 60 min p.i., compared to the 2-nitroimidazole counterpart. Though a conclusive explanation for this observation could not be obtained, present study underlined the significance of evaluating nitroimidazole radiotracers other than 2-nitroimidazole for detecting tissue hypoxia.     

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.     

Synthesis of 99mTc(CO)3-NOET via [99mTc(OH2)3(CO)3]+ precursor and comparative biological studies with 99mTcN-noet

Summary The organometallic precursor fac-[^99mTc(CO)₃(H₂O)₃]⁺ was reacted with N-ethoxy, N-ethyl dithiocarbamate (NOET) in phosphate buffered saline (pH 7.4) at room temperature for 30 minutes to produce the ^99mTc(CO)₃-NOET complex. The radiochemical purity (RCP) of the product was over 90% as measured by thin layer chromatography (TLC). No decomposition of the complex at room temperature (RT) was observed over a period of 6 hours. Its partition coefficient indicated that it was a lipophilic complex. The biodistribution comparison in mice of the ^99mTc(CO)₃-NOET complex and the ^99mTcN-NOET complex showed that the former had a lower heart and brain uptake as compared to that of the latter, suggesting the incorporation of the [^99mTc(CO)₃]⁺ core into the NOET ligand does not improve the biological features as a myocardial imaging agent.