Relative bioavailability and pharmacokinetic comparison of calcium glucoheptonate with calcium carbonate.

Adequate calcium intake is important for the prevention of bone loss and osteoporosis. For some populations such as those of Southeast Asia where calcium intake is very low, supplements represent a suitable dietary source of calcium. The objective of this study was to compare the relative oral bioavailability of calcium from calcium glucoheptonate, a highly soluble calcium salt containing 8.2% of elemental calcium, to that of calcium carbonate. A single-dose, randomized-sequence, open-label, two-period crossover study, with a 7-day washout period, was conducted in 24 Indonesian healthy adult volunteers. After a 12-hour (overnight) fast, subjects received either two oral ampoules of 250 mg/10 mL of calcium glucoheptonate each or one effervescent tablet of calcium carbonate containing 500 mg of elemental calcium. The relative oral bioavailability of calcium from calcium glucoheptonate as compared to calcium carbonate was 92% within 6 hours and 89% within 12 hours after study drug administration. The 90% confidence intervals for the mean test/reference ratios of the maximum plasma concentration and the area under the concentration-time curve at 12 hours post-administration were 77.09%-120.31% and 60.58%-122.30%, respectively. Five subjects experienced a total of eight adverse events which were all mild and transient; no serious adverse events or deaths were reported. These results indicate that calcium glucoheptonate is associated with a high relative bioavailability of calcium compared to calcium carbonate, and is well-tolerated. Calcium glucoheptonate might thus be a potential choice for calcium supplementation in Southeast Asian populations.

Imaging of the third gasotransmitter hydrogen sulfide using 99mTc-labeled alpha-hydroxy acids.

INTRODUCTION: Hydrogen sulfide (H2S) defined as the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO) is an important mediator of various physiological functions. Although various H2S-imaging techniques using fluorescence and luminescence have been developed, only one radionuclide imaging using 64Cu-labeled cyclen complex was reported. Thus, we tried to develop 99mTc-labeled H2S imaging agents. METHODS: Various α-hydroxy acids such as glycolate, L-lactate, D-lactate, D-gluconate, D-glucoheptonate, D-glucuronate, D-glucarate, and citrate were labeled with 99mTc in the presence of stannous chloride. The labeled compounds were incubated with 0.2 mM of NaHS, and reactive sulfur species and then analyzed by ITLC/normal saline to detect the formation of insoluble complex. Matrigels containing various concentrations of NaHS were xenografted on the shoulder of normal mice, and an imaging study was performed after intravenous injection of [99mTc]Tc-gluconate. We also obtained autoradiography image of a rat brain with a temporary brain ischemia after intravenous injection of [99mTc]Tc-gluconate. RESULTS: [99mTc]Tc-gluconate showed the highest formation of insoluble complex (87.8 ±â€¯3.6%) after incubation with 0.2 mM NaHS. The other reactive species such as glutathione, cysteine, sulfite, sulfate, thiosulfate, and NO did not form insoluble complex representing the reaction being specific to H2S. The Matrigel containing 2 µmol NaHS showed uptake of [99mTc]Tc-gluconate, which proved the feasibility as the specific H2S imaging agent in vivo. Temporary ischemic lesion of rat brain showed high radioactivity accumulation representing the feasibility as endogenous H2S imaging agents. CONCLUSION: We proved that 99mTc-labeled α-hydroxy acid especially [99mTc]Tc-gluconate is a novel endogenous H2S imaging agent, which might contribute to study and diagnosis of various diseases related with inflammation and hypoxia.

Tc-99m Glucoheptonate Single Photon Emission Computed Tomography-Computed Tomography for Detection of Recurrent Glioma: A Prospective Comparison with N-13 Ammonia Positron Emission Tomography-Computed Tomography.

PURPOSE OF THE STUDY: To assess the efficacies of Tc-99m glucoheptonate single photon emission computed tomography-computed tomography (Tc-99m GHA SPECT-CT) and N-13 ammonia positron emission tomography-computed tomography (N-13 NH3 PET-CT) in detecting recurrent glioma. MATERIALS AND METHODS: Fifty-five consecutive, histologically proven, and previously treated glioma patients (age, 38.9 ± 12.2 years; 61.8% males) presenting with clinical suspicion of recurrence were evaluated with Tc-99m GHA SPECT-CT and N-13 NH3 PET-CT. Images were evaluated both qualitatively and semiquantitatively. A combination of clinicoradiological follow-up, repeat imaging, and/or biopsy (when available) was considered as the reference standard. RESULTS: Based on the reference standard, 28/55 (50.9%) patients had recurrence. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy of Tc-99m GHA SPECT-CT, and N-13 NH3 PET-CT were 85.7%, 85.2%, 85.7%, 85.2%, 85.5% and 78.6%, 88.9%, 88.0%, 80.0%, 83.6%, respectively (concordant findings in 46 patients). The performances of the two modalities were equivalent both in overall and subgroup McNemar analyses (P = 0.508, overall; P = 0.687, low grade; P = 1.000, high grade). CONCLUSION: Tc-99m GHA SPECT-CT is an alternative imaging modality equally efficacious as N-13 NH3 PET-CT in detecting recurrent glioma.

Development of an HPLC/UV method for the evaluation of extractables and leachables in plastic: Application to a plastic-packaged calcium gluconate glucoheptonate solution.

Calcium gluconate glucoheptonate (GGCa) is known to interact with glass containers, leading to the leaching of aluminum from the glass into the solution at toxic level. Therefore, plastic containers seem to be a preferable packaging alternative. Nevertheless, plastics contain potentially toxic additives which could be released into the solution. In order to study content container interaction between GGCa and two plastic containers (polypropylene PP and polyethylene PE containers), an HPLC-PDA method was developed to separate, detect and quantify eleven additives commonly found in plastic materials, with good limit of detection and quantification. This method was then applied to evaluate the compatibility between GGCa and the two plastic containers. After 3 months of storage at 25 °C, none of the eleven additives were detected in GGCa solutions. The safety concern threshold (SCT) and of the analytical evaluation threshold (AET) were evaluated to discriminate the need to identify and qualify unknown peaks.

A comparison between different concentrations and sources of cobalt in goat kid nutrition.

There have been extensive studies in sheep and cattle considering cobalt (Co) supplementation and its effects on vitamin B12 concentrations in the body. However, there are limited studies on goats. The aim of this study was to compare two different sources of Co (sulfate v. glucoheptonate) at two different concentrations (0.25 and 0.5 mg/kg dry matter) in goat kid nutrition, and to evaluate the effects of these supplements on performance, serum vitamin B12, blood biochemistry and rumen volatile fatty acids. For this purpose, 30 weaned male goat kids were randomly allotted to five treatments. Serum vitamin B12 increased during the trial in the Co-supplemented groups. Co supplementation increased serum glucose concentrations. On day 35, Co-supplemented groups had greater glucose concentrations compared with control. Propionic+iso-butyric acid concentrations increased only in the 0.5 mg Co glucoheptonate treatment (P<0.05). Our results suggest that, despite the two sources of Co proving mostly similar, the main advantage of Co glucoheptonate compared with Co sulfate was in the ruminal synthesis of vitamin B12. However, although providing Co at National Research Council recommendation levels maintained vitamin B12 above or at normal concentrations, Co supplementation of the Co sufficient basal diet increased vitamin B12 and glucose concentrations.

Evaluation of Technetium-99m glucoheptonate single photon emission computed tomography for brain tumor grading.

BACKGROUND: This study is designed to appraise the diagnostic value of technetium-99m glucoheptonate (Tc-99m GHA) single photon emission computed tomography (SPECT) in brain tumor grading. SUBJECTS AND METHODS: The study was performed on 30 patients referred from the Department of Neurosurgery, who were from both urban and rural areas. Data were collected through interview, history taking, and clinical examination followed by recording the desired parameters and finally imaging. The study subjects were divided into five groups: Controls (n = 4), low-grade tumors (n = 8), high-grade tumors (n = 8), metastases (n = 5), and nonneoplastic lesions (n = 5). This division was based on the World Health Organization (WHO) classification postclinico-histological diagnosis. Each of the subjects underwent contrast-enhanced computed tomography/contrast-enhanced magnetic resonance and Tc-99m GHA SPECT preoperatively. All were followed up postoperatively, and histopathological reports were regarded as the gold standard for tumor grading wherever available. RESULTS: It was found that high-grade tumors (Grades III/IV and IV/IV according to the WHO classification) showed significantly higher tumor to normal (T/N) ratios as well as Tmax/N ratios when compared with low-grade tumors (Grades I/IV and II/IV), metastases or nonneoplastic lesions. CONCLUSIONS: In summary, the results of this study suggest that in situations where a preoperative grading of tumor is required Tc-99m GHA can be used in tumor grading and its use should be encouraged. Semi-quantitative analysis using both T/N as well as Tmax/N can be used in differentiating high-grade tumors from low-grade ones.

Use of 99m-technetium-glucoheptonate as a tracer for brain tumor imaging: An overview of its strengths and pitfalls.

Brain tumors represent a vexing clinical problem in oncology due to their increasing incidence, difficulties in treatment and high rates of recurrence. It is especially challenging to evaluate the posttreatment disease status because differentiation of recurrence from treatment-induced changes (radiation necrosis) is not possible with the use of magnetic resonance imaging, the most commonly used imaging method in this setting. Various functional imaging methods, including positron emission tomography and single photon emission computed tomography (SPECT) have been employed in this context. SPECT with 99m-technetium (99mTc)-glucoheptonate (GHA) has shown promising results for differentiation of recurrent brain tumor from radiation necrosis. In this review, we have discussed in details the basics of 99mTc-GHA SPECT imaging in brain tumor along with the available literature in this regard.

Tc-99m glucoheptonate is poor man's fluorodeoxyglucose.

While fluoro-deoxy-glucose (FDG) has emerged as an important radiotracer for imaging tumors, myocardial viability and infection, the role of other glucose analogues should also be explored. Tc-99m Glucoheptonate (GHA) has been used for imaging brain tumors and lung tumors. The uptake mechanism may be linked to GLUT-1 (Glucose transporter) and GLUT-4 expression similar to FDG. GHA is easily available and cheap. With the availability of single photon emission computed tomography/computed tomography (SPECT/CT), GHA imaging should be re-explored as a tumor agent and also for imaging myocardial viability.

The experimental study of monitoring gene-based therapy with the binding of diglycylcysteine binding motifs and 99Tcm-glucoheptonate / 中华核医学杂志

Objective To evaluate the feasibility of monitoring the gene expression of VEGF165 via the diglycylcysteine (GGC) reporter gene system by reporter probe of 99Tcm-GH. Methods DNA fragments encoding GGC binding motifs were prepared by PCR and positioned at the C end of VEGF165 gene after the linearization of pcDNA3-VEGF165 plasmid. A replication-defective adenovirus vector Ad5-VEGF165GGC motif-internal ribosomal entry site(IRES) -enhanced green fluorescent protein (EGFP) (Ad5-VIE)was constructed, with a cytomegalovirus (CMV) early promoter driving the expression of VEGF165 gene,GGC motif and EGFP, under the aid of an IRFS. A replication-defective adenovirus carrying the Ad5-EGFP was used as the control. Mensenchymal stem cells (MSC) were infected with the recombinant adenovirus at a multiplicity of infection (MOI) from 0 to 100 infectious units (0,10,25,50,100). The cellular uptake of 99Tcm-GH in infected MSC were then studied at 30, 60, 90 and 120 min. VEGF165 was detected by quantitative reverse transcriptase real-time PCR (RT-PCR), Western-blot, and immunohistochemisty. EGFP was observed by RT-PCR and fluorescence microscopy. The correlation analysis was studied between the cellular uptake of 99Tcm-GH and the expression of VEGF165. SPSS 13.0 was applied for statistical analysis. Independent samples t-test, q-test and Pearson correlation coefficient were used. Results After infected with different viral titer of Ad-VIE, the cellular uptake of 99Tcm-GH increased with the increasing virus titer(r2 =0.86, P ＜0.05), with the peak rate (7.94 ±0.75) % at MOI = 100. In time-dependent uptake study, the cellular uptake rates increased rapidly with the time extension, and the highest uptake occurred at 120 min with the peak uptake rate (7.72 ±0.22)%. The uptake rates of 99Tcm-GH in Ad5-VIE-infected cells were significantly higher than those of Ad5 -EGFP-transfected cells at all time points (t = 15.10- 54.92, all P ＜0.05). The VEGF165 and EGFP mRNA levels increased with increasing virus titer, and the VEGF165 mRNA correlated well with the EGFP mRNA(r2 = 0. 99, P ＜ 0.05). After infected with different MOI of Ad5-VIE, good relationship was found between the cellular uptake of 99Tcm-GH and the expression of VEGF165protein in MSC(r2 =0.90, P ＜0.05). Inmunohistochemisty showed VEGF165 protein expressed obviously at Ad5-VIE-infected MSC, and the EGFP was observed by fluorescence microscopy. Conclusions The cellular uptake of 99Tcm-GH in Ad5-VIE-infected MSC are well correlated with the expression of VEGF165 in vitro. The expression of therapeutic gene VEGF165 can be monitored by the GGC peptide expression.

Evaluation of Brain SPECT Using Tc-99m-Glucoheptonate and Tc-99m-HMPAO in Brain Tumors

Brain SPECT with Tc-99m-Glucoheptonate(GH) and Tc-99m-HMPAO were performed in 41 patients with brain tumors to determine the difference of uptake ratio in various histological type of tumors. SPECT studies were carried out with a rotating gamma camera in 60 minutes after intravenous injection of 15mCi of Tc-99m-GH and Tc-99m-HMPAO respectively. We counted tumor/skull(T/S) ratio on Tc-99m-GH SPECT(30 cases) and tumor/normal(T/N) ratio on Tc-99m-HMPAO SPECT(33 cases) by the use of ROI(Region of Interest) analysis. In our present study, we obtained positive uptake scans in all cases of brain tumors performed Tc-99m-GH SPECT and there was statistically significant correlation among certain type of tumor and uptake ratio. On Tc-99m-HMPAO SPECT, most of brain tumors showed decreased uptake, even in the tumors showing increased vascularity on angiographys and no definite correlation was found between tumor type and uptake ratio. Conclusively, brain SPECT with Tc-99m-GH is considered to be simple but very sensitive method in detecting brain tumors and has some value in preoperative differentiation of tumor types. Tc99m-HMPAO SPECT could be used as a tool of predicting the response to chemotherapy or radiation therapy if it was performed preoperatively and during the postoperative course.