Comparison of photoinactivation of T. rubrum by new methylene blue (NMB) and indocyanine green (EmunDo®)

BackgroundSuperficial mycotic skin infections which are predominantly caused by Trichophyton rubrum, poorly responsd to conventional therapies. A great amount of attention has focused on finding more effective treatments. The current work is aimed to compare the effectiveness of phoinactivation of Trichophyton rubrum by two relatively new photosensitizers: a phenothiazinium dye(New methylene blue) and Indocyanine green (EmunDo^®).Materials and methodsA Final inoculum of T. rubrum which corresponded to 10⁶ colony forming unit per milliliter (CFU ml⁻¹) was prepared. Antimicrobial Photodynamic treatment (aPDT) of T. rubrum was carried out by either EmunDo^® (1 mg/ml, Infra-red laser (IRL, λ = 810 nm, Energy Density 55 J/cm²)) or NMB (10 μM, Red laser (RL), λ = 630 nm, Energy Density of 5 J/cm²). The suspensions thereafter were subcultured on Sabouraud dextrose agar (SDA) and were counted on due time. based on colony-forming unit per milliliter (CFU/ml).ResultsaPDT with either EmunDo^® (E) or NMB (N) considerably diminished the viability of inoculated T. rubrum with respective reduction of 0.64 log and 0.4 log compared to the control group (P < 0.001). No significant difference was found between two laser only groups (P = 0.79) and two aPDT groups (P = 0.73), however significant reduction of T. rubrum in red laser only group (P = 0.04) and EmunDo^® only group (P = 0.04) was found as compared to the control group (P < 0.05).ConclusionThe study provides evidence regarding satisfactory photodynamic inactivation of T. rubrum with EmunDo^® or NMB as photosensitizers. Irradiation by only red laser source was found superior to only infra-red laser source. Dark toxicity of EmunDo^® was more successful than new methylene blue dye.     

Production of [18F]F2, H18F and 18Faq− using the 20Ne(d, α)18F process

Some experience relevant to the production of ¹⁸F in three chemical forms ([¹⁸F]F₂, H¹⁸F, ¹⁸F_aq⁻) via the ²⁰Ne(d, α)¹⁸F process using a Ne gas target is described. Production of [¹⁸F]F₂ and H¹⁸F was done by introducing some technical modifications in standard methods. For ¹⁸F_aq⁻ production a post irradiation target wash system was used. Methods used for the characterization of various chemical forms of radiofluorine are outlined.     

Nicotinic α4β2 receptor imaging agents. Part III. Synthesis and biological evaluation of 3-(2-(S)-azetidinylmethoxy)-5-(3'-18F-fluoropropyl)pyridine (18F-nifzetidine)

Thalamic and extrathalamic nicotinic α4β2 receptors found in the brain have been implicated in Alzheimer's disease, Parkinson's disease, substance abuse and other disorders. We report here the development of 3-(2-(S)-azetidinylmethoxy)-5-(3′-fluoropropyl)pyridine (nifzetidine) as a new putative high-affinity antagonist for nicotinic α4β2 receptors. Nifzetidine in rat brain homogenate assays containing α4β2 sites labeled with ³H-cytisine exhibited a binding affinity: Ki=0.67 nM. The fluorine-18 analog, 3-(2-(S)-azetidinylmethoxy)-5-(3′-¹⁸F-fluoropropyl)pyridine (¹⁸F-nifzetidine), was synthesized in 20%–40% yield, and apparent specific activity was estimated to be above 2 Ci/μmol. Rat brain slices indicated selective binding of ¹⁸F-nifzetidine to thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. This selective binding was displaced >85% by 150 μM nicotine. Positron emission tomography (PET) imaging studies of ¹⁸F-nifzetidine in anesthetized rhesus monkey showed slow uptake in the various brain regions. Retention of ¹⁸F-nifzetidine was maximal in the thalamus and lateral geniculate followed by regions of the temporal and frontal cortex. Cerebellum showed the least uptake. Thalamus to cerebellum ratio was about 2.3 at 180 min postinjection and continued to rise. ¹⁸F-Nifzetidine shows promise as a new PET imaging agent for α4β2 nAChR. However, the slow kinetics suggests a need for >3-h PET scans for quantitative studies of the α4β2 nAChRs.     

Intracavitary brachytherapy for carcinoma of the uterine cervix—Comparison of HDR (Ir-192) and MDR (Cs-137)—

Purpose

To compare the results of high dose rate (HDR) (Ir-192) and medium dose rate (MDR) (Cs-137) intracavitary brachytherapy (ICRT) for carcinoma of the uterine cervix.

Materials and Methods

Between May 1991 and March 2001, a total of 206 patients with Stage I-IVA previously untreated cervical cancer were treated with ICRT combined with external beam radiotherapy (EBRT). HDR was administered to a total of 135 patients: 22 patients in Stage I, 49 in Stage II, 56 in Stage III, and eight in Stage IVA. MDR was administered to a total of 71 patients: six patients in Stage I, 27 in Stage II, 33 in Stage III, and five in Stage IVA. The MDR at point A was 30 Gy/hour for HDR and 1.7 Gy/hour for MDR treatment, and the corresponding median follow-up periods for survivors were 55 and 68 months.

Results

For the HDR group, 5-year cause-specific survival rates were 90%, 78%, 53% and 33% for Stages I, II, III, and IVA, respectively. For the MDR group, the corresponding rates were 100%, 76%, 51%, and 40%. In the HDR group, 19 patients (14%) developed Grade 2 or higher late complications, and, in the MDR group, four patients (6%) did.

Conclusions

There was no statistically significant difference in cause-specific survivals between the results of HDR and MDR brachytherapy for cervical cancer. The incidence of late complications tended to be higher for the HDR group than for the MDR group, but did not show a statistically significant difference (p=0.07).     

Comparison of the response of raw wool to simultaneous neutron and γ-ray (neugat) transmission and simultaneous dual energy γ-ray (gamgat) transmission

Dual radiation beam methods are important for composition measurement where the material can be described as a binary mixture. In this paper the neutron/gamma transmission (neugat) response to the wool yield of raw wool has been determined to identify potential value in specifying this multicomponent product by this approach. A comparison is made with the gamma/gamma transmission (gamgat) method.     

Contrast-enhanced ultrasonography (CEUS) vs. MRI of the small bowel in the evaluation of Crohn’s disease activity

Purpose

The presence of disease activity in Crohn??s disease (CD) is one of the main parameters used to establish whether optimal therapy should be drug therapy or surgery. However, a major problem in monitoring CD is the common mismatch between the patient??s symptoms and imaging objective signs of disease activity. Bowel ultrasonography (US) has emerged as a low-cost, noninvasive technique in the diagnosis and follow-up of patients with CD. Accordingly, the use of contrastenhanced US (CEUS) has made possible an evaluation of the vascular enhancement pattern, similar to the use of magnetic resonance imaging (MRI). The aim of our study was to evaluate the role of CEUS in comparison with small-bowel MRI for assessing Crohn??s disease activity.

Materials and methods

We prospectively enrolled 30 consecutive patients with known CD. Clinical and laboratory data were compared with imaging findings obtained from MRI and CEUS of the small bowel. MRI was performed with a 1.5-T system using phased-array coils and biphasic orally administered contrast agent prior to and after gadolinium chelate administration. We performed US with a 7.5-MHz linear-array probe and a second-generation contrast agent. The parameters analysed in both techniques were the following: lesion length, wall thickness, layered wall appearance, comb sign, fibroadipose proliferation, presence of enlarged lymph nodes and stenosis. We classified parietal enhancement curves into two types in relation to the contrast pattern obtained with the time-intensity curves at MRI and CEUS: (1) quick washin, quick washout, (2) slow washin, plateau with a slow washout.

Results

Comparison between Crohn??s disease activity index (CDAI) and MRI showed a low correlation, with an rho=0.398; correlation between CDAI-laboratory data and CEUS activity was low, with rho=0.354; correlation between MRI activity and CEUS activity was good, with rho = 0.791; high correlation was found between CEUS and MRI of the small bowel when assessing wallthickness, lymph nodes and comb sign; good correlation was fund when assessing layered wall appearance, disease extension and fibroadipose proliferation. At MRI, timeintensity curves for 12/30 patients were active, compared with for 14/30 patients at CEUS; therefore there was a poor correlation between curve on CEUS and curve on MRI (r=0.167; p=0.36).

Conclusions

The use of CEUS can be recommended if there is a discrepancy between MRI and clinical/laboratory parameters. MRI of the small bowel remains the most accurate method for evaluating disease activity.     

Nicotinic α4β2 receptor imaging agents. Part IV. Synthesis and Biological Evaluation of 3-(2-(S)-3,4-dehydropyrrolinyl methoxy)-5-(3′-18F-Fluoropropyl)pyridine (18F-Nifrolene) using PET

Imaging agents for nicotinic α4β2 receptors in the brain have been under way for studying various CNS disorders. Previous studies from our laboratories have reported the successful development of agonist, ¹⁸F-nifene. In attempts to develop potential antagonists, ¹⁸F-nifrolidine and ¹⁸F-nifzetidine were previously reported. Further optimization of these fluoropropyl derivatives has now been carried out resulting in 3-(2-(S)-3,4-dehydropyrrolinylmethoxy)-5-(3′-Fluoropropyl)pyridine (nifrolene) as a new high affinity agent for nicotinic α4β2 receptors. Nifrolene in rat brain homogenate assays – labeled with ³H-cytisine – exhibited a binding affinity of 0.36 nM. The fluorine-18 analog, ¹⁸F-nifrolene, was synthesized in approximately 10%–20% yield and specific activity was estimated to be > 2000 Ci/mmol. Rat brain slices indicated selective binding to anterior thalamic nuclei, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. This selective binding was displaced > 90% by 300 μM nicotine. Thalamus to cerebellum ratio (> 10) was the highest for ¹⁸F-nifrolene with several other regions showing selective binding. In vivo rat PET studies exhibited rapid uptake of ¹⁸F-nifrolene in the brain with specific retention in the thalamus and other brain regions while clearing out from the cerebellum. Thalamus to cerebellum ratio value in the rat was > 4. Administration of nicotine caused a rapid decline in the thalamic ¹⁸F-nifrolene suggesting reversible binding to nicotinic receptors. PET imaging studies of ¹⁸F-nifrolene in anesthetized rhesus monkey revealed highest binding in the thalamus followed by regions of the lateral cingulated and temporal cortex. Cerebellum showed the least binding. Thalamus to cerebellum ratio in the monkey brain was > 3 at 120 min. These ratios of ¹⁸F-nifrolene are higher than measured for ¹⁸F-nifrolidine and ¹⁸F-nifzetidine. ¹⁸F-Nifrolene thus shows promise as a new PET imaging agent for α4β2 nAChR.     

Comparison of visibility of circumscribed masses on Digital Breast Tomosynthesis (DBT) and 2D mammography: are circumscribed masses better visualized and assured of being benign on DBT?

Objective

To compare the visibility of circumscribed masses on digital breast tomosynthesis (DBT) images and 2D mammograms and determine the usefulness of DBT for differentiation between benign and malignant circumscribed masses.

Methods

Seventy-one (19 malignant and 52 benign) mammographic well-circumscribed masses were included. Visibility of the masses and halo signs on DBT images were retrospectively compared with 2D mammograms. The effects of mammographic breast density on mass visibility were also evaluated.

Results

For DBT, 83% were superior and 17% were equivalent in visibility of the masses to that of 2D, and superiority of DBT was significantly enhanced in the high breast density group compared with the low breast density group (91% vs 68%, respectively, p = 0.016). Three lesions were only detected on DBT. There was no significant difference in the superiority of DBT for lesion visibility between malignant and benign masses. The halo sign was detected in 58% lesions on DBT and in 4% on 2D (p < 0.001).

Conclusion

Circumscribed masses were better visualized on DBT than on 2D mammograms, particularly in high-density breasts. The halo sign often appeared on DBT and gave a clearer mass margin. However, circumscribed masses on DBT are not assured of being benign.

Key Points

? Circumscribed masses were better visualized on breast tomosynthesis than on 2D mammography. ? Tomosynthesis visualized circumscribed masses better than 2D for all breast density categories. ? Halo signs often appeared on tomosynthesis and contributed to detect circumscribed margins. ? Circumscribed masses on tomosynthesis images are not assured of being benign lesions.

     

Efficacy and Toxicity of NN′N″N‴-tetra(2,3,4-trihydroxybenzoyl)-spermine for Decorporation of 239Pu from Mice

Summary

Male SAS/4 mice were injected i.v. with 6·6 kBq ²³⁹Pu-citrate. After 1 or 24 h a single i.p. injection of 15 or 30 μmol kg^?1 or repeated (three or four) daily injections of 30 μmol kg^?1 of tetra-THB-spermine were given, and at 4 or 7 days Pu retention was measured in liver, kidneys and femur. Besides tetra-THB-spermine, equimolar doses of tetra-DHB-spermine were injected for comparison, or equimolar doses of diethylene triamine-pentaacetic acid (DPTA) as a reference compound. Histological changes in kidneys and liver were examined after i.p. injections of 30 μmol kg^?1 or at 2–13 times higher doses of tetra-THB-spermine. The results show that: (1) Introduction of an additional hydroxy group into the aromatic moieties of tetra-DHB-spermine results in increased hydrophilicity, lower toxicity and a lower renal retention of Pu. (2) Tetra-THB-spermine and tetra-DHB-spermine are similarly effective in removing plutonium from liver and bone. Their efficacies in removing Pu from bone are approximately similar to those of DTPA but for whole-body removal they are generally inferior. (3) Multiple (30 μmol kg^?1) of tetra-THB-spermine were no more effective than a single injection at mobilizing Pu from the liver. (4) Four injections of tetra-THB-spermine induced cloudy swelling and fatty degeneration in epithelial cells of the proximal convoluted tubules. At levels of 400 μmol kg^?1 tetra-THB-spermine produced severe degenerative glomerular lesions, foci of liver necrosis and thromboses of the portal vein branch.     

Validation and assessment of the Investigator® 24plex QS kit for forensic casework application: Comparison with the PowerPlex® fusion system and GlobalFiler™ PCR amplification kits

Casework evidence samples are likely to be placed under diverse and harsh environments as compared to quantified DNA samples including serial-diluted standard DNA samples. Internal validation of a novel STR kit using casework evidence sample, which is conducted according to various conditions such as DNA contamination and degradation, is crucial before being used as a forensic application. Therefore, this study aimed to elucidate the reliability of the Investigator® 24plex QS kit through DNA derived from casework evidence and to assess whether it is applicable to STR analysis together with PowerPlex® Fusion System and GlobalFiler™ PCR Amplification Kit. DNA was extracted from 189 casework evidence samples in a total of 77 cases. The mismatch of the allelic size of this kit through allelic sizing precision test, was suitable according to ENFSI guidelines. All heterozygous balance of the three kits were above 0.6 recommended value of ENFSI guideline. The number of allele drop-in was most frequent in the GlobalFiler™ PCR Amplification Kit. In addition, the number of allele drop-out was most frequent in the Investigator® 24plex QS kit. The cutoff concentration of DNA detected in three kits of one complete STR was approximately 45 pg/μL on average. Despite of several limitations, the Investigator® 24plex QS kit is considered to have the capability to be used for STR analysis of casework evidence samples.     

Comparison of 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (FLT PET) and FDG PET/CT for the detection and characterization of pancreatic tumours

Purpose

Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3′-deoxy-3′-[¹⁸F]fluorothymidine (FLT) positron emission tomography (PET) and [¹⁸F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery.

Methods

A total of 46 patients with pancreatic tumours suspicious for malignancy and scheduled for resective surgery were recruited prospectively. In 41 patients, FLT PET and FDG PET/CT scans were performed. A diagnostic CT performed on a routine basis was available in 31 patients. FLT PET and FDG PET/CT emission images were acquired according to standard protocols. Tracer uptake in the tumour [FDG and FLT standardized uptake value (SUV)] was quantified by the region of interest (ROI) technique. For FDG PET/CT analysis, correct ROI placement was ensured via side-by-side reading of corresponding CT images.

Results

Of 41 patients, 33 had malignancy, whereas 8 patients had benign disease. Visual analysis of FDG and FLT PET resulted in sensitivity values of 91% (30/33) and 70% (23/33), respectively. Corresponding specificities were 50% (4/8) for FDG PET and 75% (6/8) for FLT PET. In the subgroup of patients with contrast-enhanced CT (n?=?31), sensitivities were 96% (PET/CT), 88% (CT alone), 92% (FDG PET) and 72% (FLT PET), respectively. Mean FLT uptake in all malignant tumours was 3.0 (range SUV_max 1.1–6.5; mean FDG SUV_max 7.9, range 3.3–17.8; p?Conclusion For differentiation of pancreatic tumours, FDG PET and FDG PET/CT showed a higher sensitivity but lower specificity than FLT PET. Interestingly, visual analysis of FLT PET led to two false-positive findings by misinterpreting physiological bowel uptake as pathological FLT uptake in the pancreas. Due to the limited number of patients, the clinical value of adding FLT PET to the diagnostic workup of pancreatic tumours remains to be determined.