Liquid metals: fundamentals and applications in chemistry.

Post-transition elements, together with zinc-group metals and their alloys belong to an emerging class of materials with fascinating characteristics originating from their simultaneous metallic and liquid natures. These metals and alloys are characterised by having low melting points (i.e. between room temperature and 300 °C), making their liquid state accessible to practical applications in various fields of physical chemistry and synthesis. These materials can offer extraordinary capabilities in the synthesis of new materials, catalysis and can also enable novel applications including microfluidics, flexible electronics and drug delivery. However, surprisingly liquid metals have been somewhat neglected by the wider research community. In this review, we provide a comprehensive overview of the fundamentals underlying liquid metal research, including liquid metal synthesis, surface functionalisation and liquid metal enabled chemistry. Furthermore, we discuss phenomena that warrant further investigations in relevant fields and outline how liquid metals can contribute to exciting future applications.

Cultural competence skills in a dental curriculum: A review.

This study aimed to analyse and evaluate the extent of transcultural content in the current curricula of the Doctor of Dental Surgery (DDS), Bachelor of Oral Health (BOH) and Master of Nursing Science (MNSc) courses at the University of Melbourne. METHODS: The study was conducted in two phases: a quantitative review and assessment of the current DDS, BOH and MNSc curricula at the University of Melbourne, and interviews with various staff from the University of Melbourne who were responsible for curriculum development for these courses. RESULTS: Staff from the DDS, BOH and MNSc courses concurred on the importance of transcultural skills, the necessity of covering cultural issues relevant to the main ethnic groups in Australia, obstacles faced and the lack of evaluation methods for cultural competency. The nursing curriculum had the most extensive coverage of transcultural content throughout both years of the course (total 71 formal contact hours; mean 36 formal contact hours per year). In contrast, modules on transcultural skills were limited to the first two of the 3-year BOH course (54 hours; 18 hours) and only the first of the 4-year dental curriculum (40 hours; 10 hours). CONCLUSION: The DDS course showed less time devoted to formal teaching of these concepts compared to the nursing and BOH courses despite showing a noticeable improvement from a previous assessment conducted in 2006. It is hoped that the DDS course continues to further increase the transcultural content and find ways to incorporate more transcultural education.

Cultural competency and communication skills of dental students: clinical supervisors' perceptions.

OBJECTIVES: This study explored clinical supervisor's (CS) views and experiences of dental students' cultural competence (CC) at the Melbourne Dental School, The University of Melbourne, Australia. Additionally, this study explored CS insights into how CC could be taught. METHODS: Semi-structured one-to-one interviews were organised with consenting CS. Interview topics included the following: the importance of CC, communication and rapport, the role of culture in oral health and the need for curriculum enhancement. Interviews were recorded, transcribed and thematically analysed to identify key areas using NVivo software. RESULTS: A total of 12 CS participated in this study. CS acknowledged the importance of CC and felt that it was important for good patient management. CS's definition of CC focused primarily on language and communication skills. CS felt that dental students were generally able to manage culturally diverse patients. However, CS indicated that additional training in this area would be beneficial. Concerns were raised about the students' ability to establish good rapport and communication, with CS highlighting areas such as misuse of interpreters and use of jargon. CS felt that clinical experience, confidence and a positive attitude are effective tools for overcoming cultural barriers. Furthermore, some CS also felt that cultural competency was a skill that is learnt through experience. CONCLUSIONS: For most CS, cultural competence was an important part of the clinician-patient exchange which would benefit from enhanced curriculum. They also highlighted areas where transcultural education could be improved. The majority of CS believed dental students managed culturally diverse patients well.

Australian/New Zealand Bachelor of Oral Health students: sociodemographics and career decisions.

This article describes the sociodemographic profile and factors affecting career decisions of Bachelor of Oral Health (BOH) students in Australia and New Zealand. Data were collected during the 2009 and 2011 academic years via online. A total of 271 students participated. The majority were female (87.8%), single (74.5%) and of Anglo-Saxon background (59.4%), and the average age was 23.7 years. The majority indicated that their fathers had at least secondary school education. The majority (52.8%) decided to study BOH after high school, and of those who commence after high school, 53.7% worked as a dental assistant/auxiliary. Career selection was self-motivated (70.2%) and a career to 'care for and help other people' (59.6%). Most respondents wished to work in a city (59.8%), in both the public and the private sectors (47.2%). This study represents a comprehensive assessment of BOH student profile in Australia and New Zealand. Findings indicate an overall different BOH student profile compared with other oral health profession students in Australia. A significant proportion had previous employment as a dental auxiliary staff and an increasing number of male students. Findings are relevant to educators, recruitment administrators and policy makers in the way the BOH profession is presented as a career option.

Penile Carcinoma in Northern Trinidad and Tobago.

OBJECTIVE: To determine the current incidence as well as general and ethnic trends of penile carcinoma in northern Trinidad and Tobago. METHODS: A retrospective analysis was conducted on all cases of penile carcinoma presenting in north and east Trinidad, as well as Tobago over an eight-year period. RESULTS: There were 19 cases from October 2003 to February 2012 with an age range of 42-96 years, mean of 59 years; peak age of presentation was 41-50 years and the number of cases presenting per year varied from one to four, with an average of three new cases yearly. Of 19 cases, 63% (12) originated from Port-of-Spain General Hospital (POSGH), 26% (5) from Sangre Grande (SGH) and 11% (2) from Tobago (TRH). There were 14 (74%) patients of African descent, three mixed and two of East Indian descent. There were four associated inflammatory lesions, five with ulcers, five verrucous lesions and two (10.5%) with human papillomavirus (HPV). One case presented with metastatic disease to the groin with erosion into the common femoral artery resulting in a blow-out of the vessel. The patient had the vessel oversewn and an extra-anatomic bypass done. He later had an above-knee amputation due to graft infection and failure. CONCLUSION: The incidence of penile carcinoma in north Trinidad and in Tobago is low and has halved in the past two decades. It stands at 0.6 cases per 100 000 males with the peak age group being 41-50 years, and with 95% of cases occurring between 41 and 80 years. There is a statistically significant association with active infection and being Afro-Caribbean. The decreasing incidence may be attributed to better hygiene, a higher rate of circumcision and low HPV rates in our population.

Paediatric dental A&E service during the COVID-19 pandemic in the Greater London area.

PURPOSE: The UK government introduced a nationwide lockdown on the 23rd March 2020 to prevent the spread of COVID-19. All elective hospital and dental practice assessments and procedures were mandated to stop. Key hospital dental workers were required to work, and Guy's and St Thomas' NHS Foundation Trust became a designated Urgent Dental Care Centre (UDC) for the greater London area. The paediatric dental emergency walk-in service was suspended and replaced with a telephone triage system and evaluation of digital images sent by parents/carers when needed. The aim of this paper is to describe the emergency service provided by staff in the department of Paediatric Dentistry at St Thomas' Hospital during the first lockdown. METHODS: A prospective service evaluation of the modified paediatric dental emergency service was carried out between 25th March and 29th May 2020. RESULTS: Four-hundred and sixty-four patients accessed the paediatric dental emergency service via telephone during the service evaluation period. Of these, 192 (41%) had dental pain, 121 (26%) had pain and swelling of dental origin, and 89 (19%) had trauma. CONCLUSIONS: Remote telephone consultations and digital photographs were useful to screen emergency paediatric dental patients, but lack of face-to-face consultations with radiographic assessment and access to general anaesthetic services were major limiting factors.

Periodontal treatment in private dental practice: a case-based survey.

BACKGROUND: This study aimed to assess the management and referral patterns of Victorian general dental practitioners based on periodontal diagnosis. METHODS: Following ethics approval, Victorian general dental practitioners were invited to complete five randomized text-based periodontitis scenario questionnaires. Based on their diagnosis, respondents were asked for their management options and asked to specify who would perform these treatments. Respondents were also asked about referral procedures. RESULTS: One hundred and thirty-five dentists attempted the survey. Most were in group practice and based in Melbourne. Of the total respondents, 22.5% worked in a practice employing a hygienist. The management of periodontal disease was appropriate, and treatment options increased with severity. As severity increased, patients were more likely to be referred to a periodontist. Periodontal services referred by general dentists to dental hygienists increased with the number of days the hygienists worked within a practice. Over- and underdiagnosis did not markedly affect management. The recommendation of antibiotics, mouthwashes and periodontal surgery varied depending on year and school of graduation. CONCLUSIONS: The general dentists that completed the survey are managing periodontal conditions appropriately and according to current guidelines.

Periodontal diagnosis in private dental practice: a case-based survey.

BACKGROUND: Despite the prevalence of periodontitis in Australia, there are few reports regarding periodontal diagnosis and therapies in the general dental practice setting. This study aimed to assess the degree of diagnostic accuracy in periodontal cases of Victorian general dental practitioners. METHODS: Following ethics approval, dentists were invited to complete a scenario-based questionnaire on the Australian Dental Association Victorian Branch (ADAVB) website. Five text-based clinical scenarios (from a total of 10) were randomly presented, representing patients with a range of disease levels from periodontal health/gingivitis to severe periodontitis, and respondents were asked what examinations they would usually perform. Based upon the presented results of periodontal and radiographic examinations, a periodontal diagnosis was requested. RESULTS: One hundred and thirty-five dentists attempted the survey. Most were in group practice and based in Melbourne; 22.5% of respondents worked in a practice employing a hygienist. The clinical parameters most commonly measured to diagnose periodontal disease were pocket depth and mobility. The majority of respondents diagnosed health, gingivitis and mild periodontitis correctly compared to American Academy of Periodontology guidelines. However, moderate periodontitis tended to be diagnosed as severe. CONCLUSIONS: Dentists in Victoria used appropriate clinical parameters when assessing periodontal disease and were generally accurate in their diagnoses. There is a need for consensus regarding diagnostic definitions.

Biosynthesis of eicosanoids by blood cells of the crab, Carcinus maenas.

Blood cells from the crab, Carcinus maenas, stimulated with calcium ionophore A23187, in the presence of exogenous fatty acid, produced cyclooxygenase, lipoxygenase and monooxygenase derivatives of eicosatetraenoic (20:4(n - 6)) and eicosapentaenoic (20:5(n - 3)) acids. Isolation, identification and quantification of these products was achieved using chiral and reverse phase-high performance liquid chromatography, gas-chromatography, radioimmunoassay and gas chromatography-mass spectrometry. The principle metabolites observed were 8-hydroxy fatty acids and 'E' series prostaglandins. Smaller amounts of thromboxane B2, 6-keto-prostaglandin F1 alpha and 5-, 9-, 11-, 12- and 15-hydroxy-eicosatetraenoic acids were also synthesised. Lipoxygenase, cyclooxygenase and cytochrome P-450 inhibitors were used to investigate the mode of product formation. Mixtures of hydroxy-fatty acid enantiomers were produced and the dominant chiral form varied with the position of the hydroxyl group. No leukotrienes or lipoxins were detected.

Synthesis of leukotriene B and other conjugated triene lipoxygenase products by blood cells of the rainbow trout, Salmo gairdneri.

Stimulation of whole blood from rainbow trout with the calcium ionophore, A23187 (20 microM), produced leukotrienes B4 and B5 at concentrations in the range 22-30 ng.ml-1 and 8-24 ng.ml-1, respectively. Their identification and quantification was achieved using reverse-phase high-performance liquid chromatography, combined capillary column gas chromatography-electron capture chemical ionization mass spectrometry and ultraviolet spectroscopy. A number of other lipoxygenase products were also detected, but only partially analysed. The fatty acid composition of the leucocytes, which are presumed to be the site of leukotriene synthesis, was determined by thin-layer and gas-liquid chromatography to enable a comparison of the relative levels of the polyunsaturated fatty acids, which act as substrates for the synthesis of these lipoxygenase products. Arachidonic (20:4(n - 6)), eicosapentaenoic (20:5(n - 3)) and docosahexaenoic (22:6(n - 3)) acids represented approx. 6, 5 and 40%, respectively, of the total fatty acid content.

Cigarette smoking: profiles of thromboxane- and prostacyclin-derived products in human urine.

Thromboxane (TX) B2, 2,3-dinor-TXB2, 11-dehydro-TXB2, 6-oxoprostaglandin (PG)F1 alpha and 2,3-dinor-6-oxo-PGF1 alpha were measured in 24 h urine samples obtained from 30 apparently healthy chronic cigarette smokers and 37 closely matched non-smoking control subjects. Samples were analysed using a newly developed assay based on immunoaffinity chromatography and capillary column gas chromatography/electron capture negative ion chemical ionisation mass spectrometry. There were significant and comparable increases in the excretion rates of both 2,3-dinor-TXB2 and 11-dehydro-TXB2 in the smoking compared with the non-smoking group (2P less than 0.001). Excretion rates of 2,3-dinor-TXB2 were 418 +/- 35 and 265 +/- 26 pg/mg creatinine in the two groups, respectively. 11-Dehydro-TXB2 excretion rates were 440 +/- 54 and 221 +/- 18 pg/mg creatinine, respectively (mean +/- S.E.). There were significant (2P less than 0.05) positive correlations between average reported cigarette consumption and excretion of both thromboxane metabolites. There were small but significant (2P less than 0.02) increases in the excretion rates of both 6-oxo-PGF1 alpha and 2,3-dinor-6-oxo-PGF1 alpha in the smoking compared with the non-smoking group. There was no significant difference in the rates of excretion of TXB2 in the two groups. The effects of acute cigarette smoke exposure (five cigarettes in 2 h) was also studied in four normally non-smoking healthy volunteers. There was no significant change in the excretion rate of any of the eicosanoids measured during control and smoking periods (at least 2 weeks apart), indicating that increased TXA2 biosynthesis in chronic smokers is unlikely to be a consequence of acute platelet activation.

Effects of dietary fatty acids on eicosanoid-generating capacity, fatty acid composition and chemotactic activity of rainbow trout (Oncorhynchus mykiss) leucocytes.

Rainbow trout, Oncorhynchus mykiss, were maintained on isocalorific diets in which either sunflower, menhaden or Fosol oils were used as the dietary source of fatty acids. At intervals over a period of 6 months, head kidney leucocytes were isolated and used for the analysis of their fatty acid composition and eicosanoid-generating capacity. Major changes in fatty acid composition were apparent within 4 weeks on the diets, with fish fed sunflower oil diets showing a 2.1-fold increase in total n-6 fatty acids and a 2.3-fold decrease in n-3 fatty acids, compared with the original basal levels. By week 8 the fatty acid composition changes were greater in the sunflower-fed fish, but thereafter remained relatively stable to the end of the experiment at week 24. Leucocytes from the fish maintained for > 8 weeks on the sunflower oil containing diet produced significantly lower percentages of 5-series lipoxygenase products derived from eicosapentaenoic acid including 12-hydroxyeicosapentaenoic acid, leukotriene B5 and lipoxin A5 compared with those cells from fish fed either menhaden or Fosol based diets. Unlike the fatty acid composition, differences in lipoxygenase product profiles between the dietary groups increased throughout the experiment and by week 24 the arachidonic acid/eicosapentaenoic acid derived product ratios were approx. 14:1 in the sunflower oil-fed fish compared with approx. 1:1.5 in the menhaden oil-fed fish. A functional consequence of these differing ratios was seen in the ability of supernatants containing these products to cause the in vitro locomotion of trout neutrophils. Supernatants from sunflower oil-fed fish were less chemo-attractive than supernatants from menhaden or Fosol oil-fed fish.

Eicosanoid generation and effects on the aggregation of thrombocytes from the rainbow trout, Oncorhynchus mykiss.

Fish blood lacks anucleate platelets but contains a nucleated cell type termed the thrombocyte that is thought to be functionally analogous. Thrombocytes were purified from the peripheral blood of the rainbow trout, Oncorhynchus mykiss, by a two step gradient centrifugation method. Following this procedure, the recovered thrombocytes were 78-86% pure as defined by immunoreactivity to a panel of monoclonal antibodies and were of variable morphology from round to spindle-shaped. Incubation of thrombocyte suspensions with either calcium ionophore, A23187, platelet-activating factor or a thromboxane (TX) mimetic, U-46619, generated a range of eicosanoids derived from arachidonic acid including 12-hydroxyeicosatetraenoic acid (12-HETE), TXB2, prostaglandin (PG) E2, leukotriene (LT) B4 and lipoxin (LX) A4. The equivalent products derived from eicosapentaenoic acid were also formed. Co-incubation of thrombocytes with either erythrocytes or granulocytes/monocytes in the presence of calcium ionophore did not result in the formation of any further new lipoxygenase products. Incubation of isolated thrombocytes in plasma-free conditions with U-46619 (0.03-10 microM) resulted in a rapid, dose-dependent aggregatory response. This effect was markedly augmented in the presence of mammalian fibrinogen (400 micrograms ml-1). Thrombin (0.1-1.3 units ml-1), like U-46619, was also a potent proaggregatory compound for trout thrombocytes. LXA4 and LTB4 had limited aggregatory potential and then only at high concentrations (10 microM), while 12-HETE and PAD had no significant effect at all concentrations tested. These results demonstrate that some of the eicosanoids released during the activation of trout thrombocytes are involved in the aggregatory behaviour of this cell type.

Effect of lipoxins and other eicosanoids on phagocytosis and intracellular calcium mobilisation in rainbow trout (Oncorhynchus mykiss) leukocytes.

Rainbow trout (Oncorhynchus mykiss) macrophages generated lipoxin (LX) A4, LXA5, leukotriene (LT) B4, LTB5 and 12-hydroxyeicosatetraenoic acid (12-HETE) during the phagocytosis of zymosan and Escherichia coli, but not of the yeast Saccharomyces cerevisiae. Prostaglandin (PG) E2 was also detected in supernatants from macrophages incubated with either zymosan or calcium ionophore A23187. LXA4 (10(-8)-10(-6) M) and LTB4 (10(-9)-10(-7) M) provoked rapid and transient dose-dependent increases in intracellular calcium ([Ca]i) concentrations in leukocyte suspensions containing 40-60% macrophages. EC50 values were 14.9 and 1.2 nM, respectively. PGE2 and 12-HETE had no effect on [Ca]i at concentrations up to 30 microM. PGE2 and 12-HETE (10(-5)-10(-10) M) enhanced the in vitro phagocytosis of yeast test particles by trout macrophages, whereas LXA4 and LTB4 had no demonstrable effect on the responses of these cells at concentrations up to 10(-5) M. In conclusion, the processes involved in trout macrophage stimulation are complex but involve generation of both cyclooxygenase and lipoxygenase products. The increase in [Ca]i caused by LXA4 and LTB4 may form part of the chemotactic transduction mechanism that recruits granulocytes and macrophages to sites of inflammation. The effects of eicosanoids on phagocytosis appear to be independent of changes in [Ca]i.

Prostacyclin and thromboxane biosynthesis in mild essential hypertension.

The possibility that prostacyclin or thromboxane biosynthesis is abnormal in patients with established mild essential hypertension was investigated in 46 patients. These eicosanoids have opposing effects both on vascular smooth muscle and on platelets. An imbalance in their biosynthesis could therefore influence both vascular tone and predisposition to thrombosis. We studied the relation between blood pressure and the biosynthesis of prostacyclin and thromboxane A2 by measuring urinary excretion rates of stable breakdown products of prostacyclin (6-oxo-prostaglandin F1 alpha and 2,3-dinor-6-oxo-prostaglandin F1 alpha) and of thromboxane A2 (thromboxane B2 and 2,3-dinor-thromboxane B2) using immunoaffinity chromatography and gas chromatography/electron capture mass spectrometry. Excretion rates of both of the prostacyclin-derived products ranged from less than 5 to more than 100 ng/g creatinine; each was significantly negatively correlated with blood pressure (r = 0.36-0.45). A reduction of 2,3-dinor-6-oxo-prostaglandin F1 alpha excretion of 100 ng/g creatinine was associated with an increase in arterial pressure of 14 mm Hg (systolic) and 8 mm Hg (diastolic) in patients who had been without antihypertensive medication for 2 weeks. The same reduction in 6-oxo-prostaglandin F1 alpha excretion was associated with an increased pressure of 19 mm Hg (systolic) and 12 mm Hg (diastolic) (2p less than 0.05 for diastolic pressure and 2p less than 0.01 for systolic pressure in each case). There were similar correlations between the excretion rates of these products and blood pressure in the same patients while they were receiving antihypertensive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Thromboxane A2 receptor antagonism and synthase inhibition in essential hypertension.

Short-term effects of ridogrel, a combined thromboxane synthase inhibitor and receptor antagonist, were investigated in 16 patients with uncomplicated essential hypertension. After a 2-week placebo period without antihypertensive medication, patients were admitted to the hospital overnight on two occasions 3 weeks apart. On each occasion, they received two doses of either placebo or ridogrel (300 mg) 12 hours apart according to a double-blind crossover protocol. Renal and systemic thromboxane A2 and prostacyclin biosynthesis were investigated by measuring urinary excretion of thromboxane B2, 6-oxo-prostaglandin F1 alpha, and their respective 2,3-dinor metabolites using gas chromatography/mass spectrometry. Responses of platelets to a thromboxane A2 mimetic and to adenosine diphosphate were studied turbidometrically. Blood pressure was measured automatically at 20-minute intervals. Ridogrel reduced excretion of 2,3-dinor-thromboxane B2 and thromboxane B2 compared with placebo (21 +/- 6 versus 279 +/- 28 and 14 +/- 4 versus 39 +/- 9 ng/g creatinine, respectively; P < .0001 and P < .05). Excretion of 2,3-dinor-6-oxoprostaglandin F1 alpha and 6-oxoprostaglandin F1 alpha was increased by ridogrel compared with placebo (184 +/- 20 versus 146 +/- 11 and 86 +/- 9 versus 58 +/- 6 ng/g creatinine, respectively; P < .05). Ridogrel selectively antagonized platelet aggregation to the thromboxane mimetic (P < .0001). Blood pressure did not differ significantly between ridogrel and placebo treatment periods. Thus, in patients with essential hypertension, acute administration of ridogrel reduces renal and extrarenal thromboxane A2 biosynthesis, increases renal and extrarenal prostacyclin biosynthesis, inhibits thromboxane receptor-activated platelet aggregation, but has no effect on systemic arterial pressure.

Prostacyclin concentrations in cord blood and in the newborn.

The levels of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) were measured in cord blood and in peripheral venous blood in newborns using gas chromatography coupled with negative ion chemical ionization mass spectrometry. The plasma concentrations of 6-oxo-PGF1 alpha in cord blood increased significantly between delivery and placental expulsion (P less than .005). In newborns, the circulation levels of 6-oxo-PGF1 alpha after four hours of life were low and comparable to adult levels. Large quantities of prostacyclin are produced by the uteroplacental unit during parturition, but only small amounts are transmitted to the newborn during a normal delivery. The low plasma concentrations of 6-oxo-PGF1 alpha in newborns suggest that prostaglandin I1 is not a circulating vasodilator during the first week of life.

Localization of radiolabeled chemotactic peptide at focal sites of Escherichia coli infection in rabbits: evidence for a receptor-specific mechanism.

UNLABELLED: The infection imaging properties of a high-affinity 99mTc-labeled chemotactic peptide receptor agonist (N-formyl-methionyl-leucyl-phenylalanine-lysine; N-For-MLFK) were compared with a low-affinity agonist (N-Acetyl-MLFK; N-Ac-MLFK), a moderate-affinity antagonist (N-isobutyloxycarbonyl-MLFK; N-IBoc-MLFK) and non-specific inflammation imaging agents. METHODS: All peptides were prepared by solid-phase methods and purified by high-performance liquid chromatography. The products were assayed in vitro for N-formyl-methionyl-leucyl-phenylalanine receptor binding and superoxide production. Three types of studies were performed in rabbits with Escherichia coli infection: (Study A) Four groups of six animals were coinjected with 99mTc-N-For-MLFK-hydrazinonicotinamide (N-For-MLFK-HYNIC) plus 111In-immunoglobulin G, 111In-red blood cells or 111In-diethylene triamine pentaacetic acid. (Study B) Three groups of six rabbits were coinjected with 111In-leukocytes plus 99mTc-N-For-MLFK-HYNIC, 99mTc-N-Ac-MLFK-HYNIC or 99mTc-N-IBoc-MLFK-HYNIC. (Study C) Two groups of six rabbits were injected with 99mTc-N-For-MLFK-HYNIC and 111In-leukocytes with and without an excess of antagonist. In all three studies, the radiopharmaceuticals were injected 24 hr after infection and dual photon (99mTc and 111In) gamma camera images were acquired at 2-3 and 16-18 hr later. Target-to-background (T/B) ratios were calculated for regions of interest drawn over the infected and contralateral normal tissue. RESULTS: N-For-MLFK, N-Ac-MLFK and N-IBoc-MLFK had EC50s for receptor binding of 2.0, 830 and 150 nM, respectively. The corresponding EC50s for superoxide production were 20.0, approximately 10(3) and > 10(4). Study A demonstrated that the T/B for 99mTc-N-For-MLFK-HYNIC was higher than for any of the nonspecific imaging agents (p < 0.001), and 111In-immunoglobulin G had a higher T/B ratio than 111In-diethylenetriamine pentaacetic acid (p < 0.01) or 111In-red blood cells (p = NS). Study B showed that 99mTc-N-For-MLFK-HYNIC had a higher T/B ratio than the other peptides (p < 0.001). 111In-leukocytes and 99mTc-N-IBoc-MLFK-HYNIC had comparable T/B ratios, which were higher than for 99mTc-N-Ac-MLFK-HYNIC (p < 0.05). Study C demonstrated that coinjection with an antagonist resulted in a significant reduction in the T/B ratio for 99mTc-N-For-MLFK-HYNIC (p < 0.001), but did not affect the T/B ratio for 111In-leukocytes. CONCLUSION: Nonspecific mechanisms contribute minimally to the localization of 99mTc-chemotactic peptide analogs at sites of infection and the majority of the accumulation appears to be receptor mediated. Also, chemotactic peptide receptor antagonists can be used for infection imaging. These results provide important new insights for future radiopharmaceutical development.

Biodistribution and dosimetry of technetium-99m-hydrazino nicotinamide IgG: comparison with indium-111-DTPA-IgG.

UNLABELLED: The biological behavior of human polyclonal immunoglobulin G (IgG), radiolabeled with 99mTc via a nicotinyl hydrazine derivative (99mTc-HYNIC-IgG), was evaluated in normal human subjects. METHODS: Initial biodistribution and dosimetry studies were performed in six normal male volunteers. Additionally, 99mTc-IgG and 111In-DTPA-IgG were co-injected into six subjects and scintillation camera images were acquired at 6 and 18 hr later and serial blood and urine samples were collected. Biodistribution of both radiopharmaceuticals were measured by region of interest analysis. In the dual-injection group, images were crossover-corrected. RESULTS: All subjects tolerated injection of the radiolabeled IgG preparations without apparent ill effects. Biodistribution of the two antibody preparations were remarkably similar with an increase in liver and abdominal activity for the 111In preparation. Linear correlation of the tissue-to-blood ratios of 99mTc and 111In-labeled IgG was observed at both times (r2 > 0.98). The slopes of the regression line were 0.97 and 0.76 at 6 and 18 hr, respectively. The beta phase of the blood clearance of 99mTc-HYNIC-IgG was significantly delayed (p < 0.01) compared with 111In-IgG (t1/2: 51.9 +/- 6.5 versus 35.3 +/- 3.4 hr). In contrast, the volumes of redistribution and urinary excretions of the radiopharmaceuticals were not significantly different. CONCLUSION: These studies establish that the biodistribution of 99mTc-HYNIC-IgG in normal human subjects is nearly identical to 111In-DTPA-IgG.