Synthesis and Bioevaluation of Novel Technetium-99m-Labeled Complexes with Norfloxacin HYNIC Derivatives for Bacterial Infection Imaging.

To seek a novel 99mTc-labeled quinolone derivative for bacterial infection SPECT imaging that aims to lower nontarget organ uptake, a novel norfloxacin 6-hydrazinoicotinamide (HYNIC) derivative (HYNICNF) was designed and synthesized. It was radiolabeled with different coligands, such as tricine, trisodium triphenylphosphine-3,3',3″-trisulfonate (TPPTS), sodium triphenylphosphine-3-monosulfonate (TPPMS), and ethylenediamine-N,N'-diacetic acid (EDDA), to obtain three 99mTc-labeled norfloxacin HYNIC complexes, namely, [99mTc]Tc-tricine-TPPTS-HYNICNF, [99mTc]Tc-tricine-TPPMS-HYNICNF, and [99mTc]Tc-EDDA-HYNICNF. These complexes were purified (RCP > 95%) and evaluated in vitro and in vivo for targeting bacteria. All three complexes are hydrophilic, maintain good stability, and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection demonstrated that [99mTc]Tc-EDDA-HYNICNF showed a higher abscess uptake and lower nontarget organ uptake and was able to distinguish bacterial infection and sterile inflammation. Single photon emission computed tomography (SPECT) image study in bacterial infection mice showed there was a visible accumulation in the infection site, suggesting that [99mTc]Tc-EDDA-HYNICNF is a potential radiotracer for bacterial infection imaging.

Radiolabeling and evaluation of a novel [99mTcN]2+ complex with deferoxamine dithiocarbamate as a potential agent for bacterial infection imaging.

In order to find a 99mTc-labeled deferoxamine radiotracer for bacterial infection imaging, deferoxamine dithiocarbamate (DFODTC) was successfully synthesized and it was radiolabeled with [99mTcN]2+ core to prepare the 99mTcN(DFODTC)2 complex. 99mTcN(DFODTC)2 was obtained with high radiochemical purity without further purification. The complex was lipophilic and exhibited good in vitro stability. According to the result of bacterial binding study, the binding of 99mTcN(DFODTC)2 to bacteria was specific. Biodistribution in mice study indicated that 99mTcN(DFODTC)2 had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses at 120 min after injection, which showed that the radiotracer could differentiate between bacterial infection and sterile inflammation. SPECT/CT images showed that there was a clear accumulation in infection sites, suggesting that 99mTcN(DFODTC)2 could be a potential bacterial infection imaging radiotracer.

Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents.

To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [99mTc][Tc(I)]+ core to obtain [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF were specific to bacteria. Compared with [99mTc]Tc-CN4NF, biodistribution studies of [99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.

Preparation and Bioevaluation of Novel 99mTc-Labeled Complexes with a 2-Nitroimidazole HYNIC Derivative for Imaging Tumor Hypoxia.

To develop novel 99mTc-labeled single-photon emission computed tomography (SPECT) radiotracers for imaging hypoxia, a novel HYNICNM ligand (6-hydrazinonicotinamide (HYNIC) 2-nitroimidazole derivative) was designed and synthesized. It was radiolabeled with technetium-99m using tricine/trisodium triphenylphosphine-3,3',3''-trisulfonate (TPPTS), tricine/sodium triphenylphosphine-3-monosulfonate (TPPMS) and tricine as co-ligands to obtain [99mTc]Tc-tricine-TPPTS-HYNICNM, [99mTc]Tc-tricine-TPPMS-HYNICNM, and [99mTc]Tc-(tricine)2-HYNICNM, respectively. The three technetium-99m complexes were radiolabeled in one step with a high yield (95%) and had good stability in saline and mouse serum. In vitro cellular uptake results showed that these complexes exhibited good hypoxic selectivity. The partition coefficient indicated that they were good hydrophilic complexes, and [99mTc]Tc-tricine-TPPTS-HYNICNM displayed the highest hydrophilicity (-3.02 ± 0.08). The biodistribution in mice bearing S180 tumors showed that [99mTc]Tc-tricine-TPPTS-HYNICNM exhibited higher tumor uptake (1.05 ± 0.27% IA/g); more rapid clearance from the liver, blood, muscle, and other non-target organs; and a higher tumor/non-target ratio, especially for the tumor/liver ratio (1.95), than [99mTc]Tc-tricine-TPPMS-HYNICNM and [99mTc]Tc-(tricine)2-HYNICNM. The results of single-photon emission computed tomography (SPECT) imaging studies of [99mTc]Tc-tricine-TPPTS-HYNICNM were in accordance with the biodistribution results, which suggested that [99mTc]Tc-tricine-TPPTS-HYNICNM is a promising agent for imaging tumor hypoxia.

99mTc-CN7DG: A Highly Expected SPECT Imaging Agent of Cancer with Satisfactory Tumor Uptake and Tumor-to-Nontarget Ratios.

A novel glucose derivative (CN7DG) possessing an isonitrile as a coordinating group was synthesized, and 99mTc-CN7DG, which was expected to be a powerful tumor imaging agent for SPECT, was prepared in a kit by the reaction of CN7DG with SnCl2·2H2O and 99mTcO4-. 99mTc-CN7DG exhibited good stability and was transported via glucose transporters. Biodistribution results in mice bearing A549 tumor models showed that 99mTc-CN7DG had a higher uptake at the tumor sites and better tumor/blood and tumor/muscle ratios than did [18F]FDG and 99mTc-CN5DG. SPECT/CT imaging studies showed obvious accumulation in tumor sites, suggesting that 99mTc-CN7DG is a promising candidate for tumor imaging. Because 99mTc and 188Re stand for a "theranostic pair", 188Re-CN7DG is expected to be prepared as a promising agent for tumor therapy.

Design, Preparation, and Evaluation of a Novel 99mTcN Complex of Ciprofloxacin Xanthate as a Potential Bacterial Infection Imaging Agent.

In order to seek novel technetium-99m bacterial infection imaging agents, a ciprofloxacin xanthate (CPF2XT) was synthesized and radiolabeled with [99mTcN]2+ core to obtain the 99mTcN-CPF2XT complex, which exhibited high radiochemical purity, hydrophilicity, and good stability in vitro. The bacteria binding assay indicated that 99mTcN-CPF2XT had specificity to bacteria. A study of biodistribution in mice showed that 99mTcN-CPF2XT had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses, indicating that it could distinguish bacterial infection from sterile inflammation. Compared to 99mTcN-CPFXDTC, the abscess/blood and abscess/muscle ratios of 99mTcN-CPF2XT were higher and the uptakes of 99mTcN-CPF2XT in the liver and lung were obviously decreased. The results suggested that 99mTcN-CPF2XT would be a potential bacterial infection imaging agent.

Synthesis and evaluation of [99mTcN]2+ core and [99mTcO]3+ core labeled complexes with 4-nitroimidazole xanthate derivative for tumor hypoxia imaging.

A 4-nitroimidazole xanthate ligand (NMXT) was synthesized and radiolabeled with [99mTcN]2+ core and [99mTcO]3+ core to obtain 99mTcN-NMXT and 99mTcO-NMXT, respectively. The two 99mTc-complexes were prepared with high radiochemical purity and had good stability. The partition coefficient results indicated both of them were hydrophilic, and cellular uptake studies showed they exhibited good hypoxic selectivity. From the biodistribution study results, 99mTcO-NMXT showed more favourable tumor uptake (1.73 ± 0.14 ID%/g) and higher tumor/muscle ratio (7.01 ± 0.16) than 99mTcN-NMXT at 4 h post-injection. Single photon emission computed tomography (SPECT) imaging study of 99mTcO-NMXT showed there was a visible accumulation in tumor site, suggesting it would be a promising candidate as a tumor hypoxia imaging agent.

Novel 99mTc-labelled complexes with thymidine isocyanide: radiosynthesis and evaluation as potential tumor imaging tracers.

A novel thymidine isocyanide (CN-TdR) functionalized at the N3 position of thymidine was synthesized and then radiolabelled with 99mTc(i) and [99mTc(i)(CO)3]+ cores to produce [99mTc(CN-TdR)6]+ and [99mTc(CO)3(CN-TdR)3]+, respectively. Both of them were prepared with high radiochemical purity and were stable over 6 h in saline at ambient temperature and in serum at 37 °C. The partition coefficient results demonstrated that they were hydrophilic. The cell internalization studies showed that their uptake might be mediated by nucleoside transporters. Biodistribution of these complexes in mice bearing the S180 tumor showed that they accumulated in the tumor with high uptake and cleared rapidly from blood and muscles, producing high tumor/blood and tumor/muscle ratios. Between them, [99mTc(CN-TdR)6]+ exhibited advantages concerning a higher tumor uptake, tumor/blood ratio and tumor/muscle ratio at 60 min post-injection. Single photon emission computed tomography imaging studies showed that there was a clear accumulation in tumor sites, suggesting that [99mTc(CN-TdR)6]+ could be a promising candidate for tumor imaging.

[Research on the ultraviolet reflectivity characteristic of simulative targets of oil spill on the ocean].

The authors set up an experiment instrument to measure the ultraviolet (UV) characteristic of oil spill simulation targets for the marine oil spill. After selecting appropriate conditions for experiments, the authors tested UV reflective spectrum of four simulation targets for oil spill (gasoline, kerosene, diesel fuel, lubricating oil). The authors calculated the UV absolute spectrum reflectivity of all testing targets from the standard white board as reference, whose UV reflectivity was given. With processing and analyzing the data from experiments, the authors got the reflective characteristics of them in contrast to the reflectivity of water, which was measured in the same conditions. All targets were tested from 320 to 400 nm, and UV reflectivity wave-band between 360 and 380 nm was representative. Testing data were shown as follows: (1) The reflectivity of water was from 5.3% to 5.5%. (2) When the thickness of oil film was 400 microm, the reflectivity of gasoline was from 8.5% to 8.8%, 5.4%-5.8% for kerosene, 8.3%-8.4% for diesel fuel, and 9.4%-9.7% for lubricating oil in the same wave-band between 360 and 380 nm. Correspondingly, the indeterminacy of reflectivity was 0.32%, 0.45%, 0.25%, and 0.33% respectively. (3) Hence the thickness of oil film changed, the rule of the UV reflectivity varied depending on the sort of oil spill. The results show that there were some obvious reflectivity differences among oil films and water, which were mainly determined by the sort and thickness of oil film. This experiment method is also fit for the actual oil spill target, and it will fulfill some theory and experimental foundation for inspecting the marine oil spill by UV remote sensing in the future.