[Morphological and biochemical characterization during seed development of Notopterygium incisum].

This study aimed to examine the morphological, physiological, and biochemical alterations occurring in Notopterygium incisum seeds throughout their developmental stages, with the objective of establishing a theoretical foundation for the cultivation of superior quality seeds. The experimental materials utilized in this study were the seeds of N. incisum at various stages of development following anthesis. Through the employment of morphological observation and plant physiology techniques, the external morphology, nutrients, enzyme activity, and endogenous hormones of the seeds were assessed. The results revealed a transition in seed coat color from light green to brown during the growth and development of N. incisum seeds. Additionally, as the seeds matured, a decrease in water content was observed. Conversely, starch content exhibited a progressive increase, while sucrose content displayed fluctuations. At 7 days after anthesis, the soluble sugar content attained its highest level of 4.52 mg·g~(-1), whereas the soluble protein content reached its maximum of 6.00 mg·g~(-1) at 14 days after anthesis and its minimum of 4.94 mg·g~(-1) at 42 days after anthesis. The activity of superoxide dismutase(SOD) exhibited an initial increase, followed by a decrease, and eventually reached a stable state. Conversely, the activities of catalase(CAT) and peroxidase(POD) demonstrated a decrease initially, followed by an increase, and then another decrease. The levels of the four endogenous hormones, namely gibberellin(GA_3), zeatin riboside(ZR), auxin(IAA), and abscisic acid(ABA), in the seeds displayed significant variations, with IAA and ABA exhibiting considerably higher levels compared to the other hormones. The levels of plant growth-promoting hormones, represented by IAA, generally displayed a pattern of initial increase followed by a subsequent decrease during seed development, while the plant growth-inhibiting hormone ABA showed the opposite trend. The findings indicate that the alterations in nutrient composition, antioxidant enzyme activity, and endogenous hormone levels vary throughout the maturation process of N. incisum seeds. These observations hold relevance for the cultivation of N. incisum seeds.

The Preparation and Execution of Exploratory Human Studies on Novel 99mTc-Labeled Glucosamine Derivatives Containing Different Phenyl Isonitriles as Promising Tumor Imaging Agents.

As the "molecule of the century", 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) is a radioactive 18F-labeled glucose derivative with a wide range of applications for positron emission tomography (PET) imaging. Single photon emission computed tomography (SPECT) imaging is widely used, but there is no clinical probe comparable to [18F]FDG. In our previous work, [99mTc]Tc-CN5DG and [99mTc]Tc-CN7DG were successfully developed and achieved high-quality SPECT images. However, they still have the disadvantage of low tumor uptake and/or high uptake by nontarget organs. To develop novel tumor imaging agents with high tumor uptake and excellent tumor/nontarget ratios, in this study, starting from d-glucosamine hydrochloride, four phenyl group-containing isonitrile ligands were designed, synthesized, and radiolabeled with 99mTc. All the complexes had high radiochemical purity and good hydrophilicity and stability. Biodistribution experiments showed that [99mTc]Tc-L4 (i.e., [99mTc]Tc-CNMBDG) had the highest tumor uptake and tumor/background ratios among the four probes. In SPECT imaging studies, the tumor detected by [99mTc]Tc-L4 was more clearly visible than that of [99mTc]Tc-CN7DG because of the inappreciable interference from abdominal uptake. Preliminary clinical studies of [99mTc]Tc-L4 have been conducted and successfully showed the lesion location in a patient with non-small-cell lung cancer. In summary, [99mTc]Tc-L4 is expected to be a promising tumor SPECT imaging agent.

Development of a 18F-Labeled Bicyclic Peptide Targeting EphA2 for Molecular Imaging of PSMA-Negative Prostate Cancer.

Although PSMA PET/CT imaging has great potential for noninvasively detecting prostate cancer (PCa), limitations exist for patients with low PSMA expression, caused by androgen deprivation treatment or neuroendocrine differentiation. Analysis of The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data found that erythropoietin-producing hepatocellular receptor A2 (EphA2), a receptor overexpressed in most PCa could be a potential target for PSMA-negative PCa. A fluorescent ligand ETF and a radiolabeled ligand [18F]AlF-ETN derived from a EphA2-targeting bicyclic peptide were synthesized and investigated. ETF could selectively stain and visualize the EphA2-positive but PSMA-negative PC3 cells, in complementary to the PSMA-targeting probe. PET/CT imaging and biodistribution experiments demonstrated that [18F]AlF-ETN specifically accumulated in PC3 tumors with a high contrast (tumor-to-muscle ratio: 21.29 ± 6.55). In conclusion, we have demonstrated the potential for using EphA2 to detect PSMA-negative PCa and developed a radiolabeled ligand [18F]AlF-ETN to specifically image EphA2 expressing PCa with high contrast.

Preparation and Evaluation of [18F]AlF-NOTA-PBB for PET Imaging of Cyclin-dependent Kinase 4/6 in Tumors.

Cyclin-dependent kinases (CDKs), especially cyclin-dependent kinase 4/6 (CDK4/6), have been targets for the development of specific tumor imaging agents. Palbociclib is a highly selective CDK4/6 inhibitor. In this study, to develop a novel 18F-labeled palbociclib derivative for specific tumor imaging, we designed and synthesized a ligand (NOTA-PBB) consisting of palbociclib as the targeted pharmacophore and NOTA as the macrocyclic bifunctional chelator. The corresponding [18F]AlF-NOTA-PBB complex was prepared with high radiochemical purity (98.4 ± 0.15%) and yield (58.7 ± 4.5%) within 35 min without requiring HPLC purification through a simple one-step 18F-labeling strategy of NOTA-AlF chelation chemistry. The radiotracer was lipophilic (log P = 0.095 ± 0.003) and had good stability in vitro and in vivo. The cellular uptake studies performed on the MCF-7 breast cancer cell line (ER-positive and HER2-negative) showed that radioactive uptake was blocked by preincubating with a molar dose of palbociclib and it had a nanomolar binding affinity to CDK4/6 (IC50 = 16.23 ± 1.84 nM), demonstrating a CDK4/6-mediated uptake mechanism. Its ex vivo biodistribution in nude mice-bearing MCF-7 tumors showed obvious tumor uptake and a high tumor/muscle ratio of [18F]AlF-NOTA-PBB, and tumor uptake was inhibited with 100 µg of palbociclib, demonstrating specific binding to CDK4/6. Radioactivity accumulation in MCF-7 tumors was observed in PET imaging with [18F]AlF-NOTA-PBB. Based on the results of this work, [18F]AlF-NOTA-PBB has the promising capability as a CDK4/6-targeted tumor imaging agent.

99mTc-HFAPi imaging identifies early myocardial fibrosis in the hypertensive heart.

BACKGROUND: This study aimed to explore whether 99mTc-radiolabeled fibroblast activation protein inhibitor (99mTc-HFAPi) imaging can detect early myocardial fibrosis in the hypertensive heart. METHODS: In the experimental model, spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto rats (WKYs) were randomly divided into three groups (8, 16, and 28 weeks). The animals underwent 99mTc-HFAPi imaging and echocardiography. Autoradiography and histological analyses were performed in the left ventricle. The mRNA and protein expression level of the fibroblast activation protein (FAP) and collagen I were measured using quantitative PCR and western blot. In the clinical investigation, a total of 106 patients with essential hypertension and 20 gender-matched healthy controls underwent 99mTc-HFAPi imaging and echocardiography. RESULTS: In-vivo and in-vitro autographic images demonstrated diffusely enhanced 99mTc-HFAPi uptake in the SHR heart starting at week 8, before irreversible collagen deposition. The mRNA and protein levels of FAP in SHRs began to increase from week 8, whereas changes in collagen I levels were not detected until week 28. In the clinical investigation, even in hypertensive patients with normal diastolic indicators, normal left ventricular geometry, and normal global longitudinal strain (GLS), the prevalence of increased 99mTc-HFAPi uptake reached 34, 41, and 20%, respectively, indicating that early fibrogenesis precedes structural and functional myocardial abnormalities. CONCLUSION: In hypertension, 99mTc-HFAPi imaging can detect early fibrotic process before myocardial functional and structural changes.

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.

Evaluation of 99mTc-CN5DG as a broad-spectrum SPECT probe for tumor imaging.

Previously, we reported a [99mTc(ǀ)]+ labeled d-glucoamine derivative (99mTc-CN5DG) and evaluated it as a tumor imaging agent in mice bearing A549 tumor xenografts. In this paper, 99mTc-CN5DG was further studied in U87 MG (human glioma cells), HCT-116 (human colon cancer cells), PANC-1 (human pancreatic cancer cells) and TE-1 (human esophageal cancer cells) tumor xenografts models to verify its potential application for imaging of different kinds of tumors. The biodistribution data showed that 99mTc-CN5DG had a similar biodistribution pattern in four tumor models at 2 h post-injection with high accumulation in tumors and kidneys. The tumor/muscle ratios (from 4.08 ±â€¯0.42 to 9.63 ±â€¯3.53) and tumor/blood ratios (from 17.18 ±â€¯7.40 to 53.17 ±â€¯16.16) of 99mTc-CN5DG in four tumor models were high. All four kinds of tumors could be clearly seen on their corresponding SPECT/CT images. Pharmacokinetic study in healthy CD-1 mice demonstrated that 99mTc-CN5DG cleared fast from blood (2 min, 12.97 ±â€¯0.88%ID/g; 60 min, 0.33 ±â€¯0.06%ID/g) and the blood distribution, elimination half-life was 5.81 min and 21.16 min, respectively. No abnormality was observed through the abnormal toxicity study. All of the above results demonstrated that 99mTc-CN5DG could be a broad-spectrum SPECT probe for tumor imaging and its further clinical application is warranted.

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.

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 (Ki 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.

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.

Preparation and evaluation of 99mTc-labeled HYNIC-palbociclib analogs for cyclin-dependent kinase 4/6-positive tumor imaging.

Overexpression and amplification of cyclin-dependent kinase 4/6 (CDK4/6) occur in many cancers and may be the cause of resistance to CDK4/6 inhibitors in preclinical models. However, there are few investigations on the assessment of CDK4/6 expression in tumors or other tissues. Palbociclib, which was approved in 2015 to treat ER+/HER2-breast cancer in combination with letrozole, is a selective CDK4/6 inhibitor. In this study, an intermediate (compound 3), which could be hydrolyzed into the ligand (compound L) consisting of palbociclib as the bioactive molecule and 6-hydrazino nicotinamide (HYNIC) as the bifunctional chelator, was synthesized. Compound L was radiolabeled with 99mTc using tricine/TPPTS or tricine/TPPMS as co-ligands. 99mTc-tricine-TPPTS-L and 99mTc-tricine-TPPMS-L were prepared with high radiochemical purity without postlabeling purification. They had great in vitro stability. Both radiotracers were hydrophilic, but 99mTc-tricine-TPPTS-L had a lower log P value. In vitro cell uptake studies in MCF-7 cells showed that cellular uptake was blocked by preincubation with palbociclib, suggesting a CDK4/6-mediated uptake mechanism. Biodistribution in mice bearing MCF-7 tumors showed that 99mTc-tricine-TPPTS-L had higher tumor uptake than 99mTc-tricine-TPPMS-L, while they had comparable tumor-to-muscle and tumor-to-blood ratios. Radioactivity accumulation in tumors was obvious in micro-SPECT/CT images with 99mTc-tricine-TPPTS-L. When mice were preinjected with palbociclib, tumor uptake of 99mTc-tricine-TPPTS-L significantly decreased and the tumor accumulation was clearly lost, confirming CDK4/6 specificity. All results in this work indicated that 99mTc-tricine-TPPTS-L is a promising tumor imaging agent that targets CDK4/6.

Synthesis and Biological Evaluation of Novel 99mTc-Labeled Palbociclib Derivatives Targeting Cyclin-Dependent Kinase 4/6 (CDK4/6) as Potential Cancer Imaging Agents.

Cancer results from cell proliferation that exceeds normal growth control. There are various specific proteins that control and regulate the cell cycle, such as cyclin-dependent kinases (CDKs), cyclins, and retinoblastoma protein (pRb). The aberration of the cyclin D-CDK4/6-INK4-pRb pathway occurs frequently in cancers; thus, CDK4/6 is an attractive target for the development of radiopharmaceuticals for tumor imaging. In this study, we chose palbociclib, which was approved by the FDA for treating ER+/HER2- advanced breast cancer as the target vector and the isonitrile group, which can coordinate strongly with the [99mTc(CO)3]+ core as the bifunctional chelator, to develop four novel 99mTc-labeled radiotracers for tumor imaging. The ligands (L2, L3, L4, and L5) were synthesized by reacting palbociclib with isocyanide-containing active esters and then radiolabeling with a [99mTc(CO)3]+ core to produce radiotracers (99mTc-L2, 99mTc-L3, 99mTc-L4, and 99mTc-L5) with high radiochemical purity (>95%) and good stability in vitro. The structures of the 99mTc complexes were identified by preparation and characterization of the corresponding stable rhenium complexes. Partition coefficient results indicated that these complexes were lipophilic. A kinase inhibition assay demonstrated the high affinity of the stable Re complexes for CDK4. A cell study showed that all four complexes had substantial uptake by MCF-7 cells and could be significantly inhibited by palbociclib and nonradiolabeled ligand, indicating a CDK4/6-specific uptake mechanism. Biodistribution studies in nude mice bearing MCF-7 tumors showed that the complexes had obvious accumulation in tumors at 2 h postinjection. 99mTc-L2 exhibited the highest tumor uptake and tumor/blood ratio, whereas 99mTc-L4 showed the highest tumor/muscle ratio. The micro-SPECT/CT study showed that complex 99mTc-L4 had visible uptake at the tumor site, and the accumulation was clearly reduced in the image after pretreatment with palbociclib, further indicating CDK4/6 specificity. All the results showed that the 99mTc-labeled complexes in this work have the potential for tumor imaging.

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.

Novel 99mTc-Labeled Glucose Derivative for Single Photon Emission Computed Tomography: A Promising Tumor Imaging Agent.

In this study, a d-glucosamine derivative with an isonitrile group (CN5DG) was synthesized and it was chosen to coordinate with 99mTc for preparing 99mTc-CN5DG. 99mTc-CN5DG could be readily obtained with high radiochemical purity (>95%) and had great in vitro stability and metabolic stability in urine. The radiotracer demonstrated a positive response to the administration of glucose and insulin in S180 and A549 tumor cells in vitro, suggesting the mechanism of 99mTc-CN5DG into tumor cells was related to glucose transporters. Biodistribution studies in mice bearing A549 xenografts showed 99mTc-CN5DG had a high tumor uptake and high tumor-to-background ratios. SPECT/CT images further supported its ability for tumor imaging. As a cheap, conveniently made and widely available probe, 99mTc-CN5DG would become a potential "working horse" and be a breakthrough in 99mTc-labeled radiopharmaceuticals for tumor detection.

Macrocyclic triamine derived glucose analogues for 99m Tc(CO)3 labeling: synthesis and biological evaluation as potential tumor-imaging agents.

[99m Tc(CO)3 (H2 O)3 ]+ has attracted great attention among 99m Tc-labeling techniques, due to its ease of preparation, readily substituted water molecules of the precursor fac-[99m Tc(CO)3 (H2 O)3 ]+ by a variety of functional groups, small size and inertness. Bifunctional chelator based on a macrocyclic polyamine framework shows easy complexation with [99m Tc(CO)3 (H2 O)3 ]+ to produce stable complex. In this study, two novel 1, 5, 9-triazacyclododecane derivatives containing a glucose group (6 and 7) were successfully synthesized by reacting different glucose-azides with alkyne-[12]aneN3 via the so-called click chemistry and radiolabeled with [99m Tc(CO)3 (H2 O)3 ]+ to form 99m Tc(CO)3 -6 (C-1-substituted complex) and 99m Tc(CO)3 -7 (C-2-substituted complex) in high yields. The complexes were stable in vitro over 6 h when incubated in saline at room temperature and in mouse serum at 37 °C. The partition coefficient results showed that they were hydrophilic. The biodistribution studies in Kunming mice bearing S 180 tumor showed both complexes showed accumulation in the tumor. Between them, 99m Tc(CO)3 -7 had the advantages of much higher tumor uptake and tumor/muscle ratio. Compared with other reported 99m Tc-radiolabeled glucose derivatives, 99m Tc(CO)3 -7 also showed a higher tumor uptake and tumor/muscle ratio, suggesting it would be a potential candidate for further development as a tumor-imaging agent.

A Stimuli-Responsive Biosensor of Glucose on Layer-by-Layer Films Assembled through Specific Lectin-Glycoenzyme Recognition.

The research on intelligent bioelectrocatalysis based on stimuli-responsive materials or interfaces is of great significance for biosensors and other bioelectronic devices. In the present work, lectin protein concanavalin A (Con A) and glycoenzyme glucose oxidase (GOD) were assembled into {Con A/GOD}n layer-by-layer (LbL) films by taking advantage of the biospecific lectin-glycoenzyme affinity between them. These film electrodes possess stimuli-responsive properties toward electroactive probes such as ferrocenedicarboxylic acid (Fc(COOH)2) by modulating the surrounding pH. The CV peak currents of Fc(COOH)2 were quite large at pH 4.0 but significantly suppressed at pH 8.0, demonstrating reversible stimuli-responsive on-off behavior. The mechanism of stimuli-responsive property of the films was explored by comparative experiments and attributed to the different electrostatic interaction between the films and the probes at different pH. This stimuli-responsive films could be used to realize active/inactive electrocatalytic oxidation of glucose by GOD in the films and mediated by Fc(COOH)2 in solution, which may establish a foundation for fabricating novel stimuli-responsive electrochemical biosensors based on bioelectrocatalysis with immobilized enzymes.