67Ga Uptake Research Articles

Development of Quantitative Norms for Normal Lung Uptake Based on Three-Dimensional Gallium-67 Single Photon Emission Computed Tomography/Computed Tomography

Abstract Purpose Gallium-67 (Ga-67) lung scans assess alveolitis and interstitial lung disease, with Ga-67 accumulation correlating with inflammation intensity as seen in lung biopsy sections. Both semi-quantitative and quantitative methods have been used, with the latter providing an inflammatory activity index linked to lung lavage and histopathological scores. However, differing reference points result in varying outcomes. This study aimed to establish standard Ga-67 index parameters using semi-quantitative analysis and a linear regression model based on planar and SPECT/CT images. Methods Twenty subjects without lung disease received a 5–6 mCi Ga-67 injection via the ankle. Both planar and SPECT/CT images were analyzed, with semi-quantitative values assessed using GraphPad Prism 9.5.1. Results Compared to planar images, SPECT/CT acquisitions for the lung-to-arm uptake ratio proved the most reliable indicator for assessing lung inflammation. Increased lung Ga-67 uptake was defined as greater than 2 standard deviations from the average Ga-67 uptake for healthy subjects. The normal range was 0.065 ± 0.049 for the right side and 0.076 ± 0.070 for the left side. Conclusion Lung-to-arm ratios in SPECT/CT images are more accurate than those in planar images. This method should be adopted as a standard clinical practice, providing more reliable diagnostic information and improving patient management. Future studies should compare patients without lung disease to those with lung disease to determine the diagnostic benefit of these norms.

Soil gallium speciation and resulting gallium uptake by rice plants

Gallium (Ga) is widely used in high-tech industries and is an emerging contaminant in the environment. This study aimed to determine Ga speciation in soils and Ga accumulation in rice plants (Oryza sativa L.) grown in three Ga-contaminated soils. The results showed that, among the soils, the acidic soil with a coarse texture had the highest soil Ga availability, which enhanced Ga uptake by rice roots. The Ga K-edge X-ray absorption near edge structure and sequential extraction results of the soils showed that the predominant species of Ga associated with iron hydroxides transformed to Ga(OH)3 precipitates, and the residue fraction increased with rice-growing time, resulting in lower Ga uptake by rice roots in the second half period of rice cultivation. A large fraction of Ga was accumulated in the rice roots, with only a small portion of Ga was transferred to the shoots and then to the rice grains. This study revealed that Ga speciation in soil-rice plant systems varied during rice cultivation and determined soil Ga availability to rice plants. Gallium accumulated in rice grains is distributed homogenously in the endosperm of the grains, suggesting a potential risk to public health via the intake of rice grains harvested from Ga-contaminated paddy fields.

Antibacterial Activities of Ga(III) against E.coli Are Substantially Impacted by Fe(III) Uptake Systems and Multidrug Resistance in Combination with Oxygen Levels.

The continued emergence and spread of antimicrobial resistance (AMR), particularly multidrug resistant (MDR) bacteria, are increasing threats driving the search for additional and alternative antimicrobial agents. The World Health Organization (WHO) has categorized bacterial risk levels and includes Escherichia coli among the highest priority, making this both a convenient model bacterium and a clinically highly relevant species on which to base investigations of antimicrobials. Among many compounds examined for use as antimicrobials, Ga(III) complexes have shown promise. Nonetheless, the spectrum of activities, susceptibility of bacterial species, mechanisms of antimicrobial action, and bacterial characteristics influencing antibacterial actions are far from being completely understood; these are important considerations for any implementation of an effective antibacterial agent. In this investigation, we show that an alteration in growth conditions to physiologically relevant lowered oxygen (anaerobic) conditions substantially increases the minimum inhibitory concentrations (MICs) of Ga(III) required to inhibit growth for 46 wild-type E.coli strains. Several studies have implicated a Trojan horse hypothesis wherein bacterial Fe uptake systems have been linked to the promotion of Ga(III) uptake and result in enhanced antibacterial activity. Our studies show that, conversely, the carriage of accessory Fe uptake systems (Fe_acc) significantly increased the concentrations of Ga(III) required for antibacterial action. Similarly, it is shown that MDR strains are more resistant to Ga(III). The increased tolerance of Fe_acc/MDR strains was apparent under anaerobic conditions. This phenomenon of heightened tolerance has not previously been shown although the mechanisms remain to be defined. Nonetheless, this further highlights the significant contributions of bacterial metabolism, fitness, and AMR characteristics and their implications in evaluating novel antimicrobials.

67Ga as a biosensor of iron needs in different organs: Study performed on male and female rats subjected to iron deficiency and exercise

The aim of the present study was to determine the iron needs in different organs and tissues using 67Ga as a biosensor in males and females rats subjected to iron deficiency (ID) and voluntary exercise (EX). 67Ga citrate was injected i.p. to female and male Wistar rats (n=5/sex/group). Groups: Control (sedentary conditions), Control+EX, ID and ID+EX. To determine the 67Ga uptake, samples from the following regions of interest (ROIs) were extracted 12h post-injection: blood, liver, gonads, bone marrow, heart, adrenal glands, skeletal muscle, stomach, kidney, eyeball, sciatic nerve, small intestine and peritoneum. The total 67Ga uptake was 412% higher in ID subjects than in control subjects, being 1011% higher in ID-males than ID-females. In ID-females, the ROIs with the greater 67Ga uptake were blood, kidney and bone marrow, while in ID-males they were sciatic nerve, eyeball and adrenals, which demonstrates that the biodistribution differed between sexes in sedentary conditions but when subjected to EX, the biodistribution was similar in each sex group although females had a greater 67Ga uptake. In ID+EX subjects, the ROIs that showed the highest uptake were sciatic nerve, eyeball and adrenal glands. Using 67Ga as a biosensor, it is possible to identify the needs of iron that each organ requires to perform their functions in normal physiological conditions. In addition, a higher or lower 67Ga uptake in a specific organ may indicate its malfunction or show damage.

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections.

ObjectiveTo evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 (67Ga) citrate scintigraphy.Materials and MethodsWe studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99mTc-EDDA-HYNIC-TOC, and 21 after injection of 111In-DTPA-octreotide. All patients also underwent 67Ga citrate imaging, except for one patient who died before the 67Ga was available.ResultsIn 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67Ga uptake in 11 of the 20 patients with positive images and similar to 67Ga uptake in the other 9 patients. The only patient who did not undergo 67Ga scintigraphy underwent 99mTc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis.ConclusionSPECT/CT with 99mTc-EDDA-HYNIC-TOC or 111In-DTPA-octreotide seems to be a good alternative to 67Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

AtSWEET13 and AtSWEET14 regulate gibberellin-mediated physiological processes.

Transmembrane transport of plant hormones is required for plant growth and development. Despite reports of a number of proteins that can transport the plant hormone gibberellin (GA), the mechanistic basis for GA transport and the identities of the transporters involved remain incomplete. Here, we provide evidence that Arabidopsis SWEET proteins, AtSWEET13 and AtSWEET14, which are members of a family that had previously been linked to sugar transport, are able to mediate cellular GA uptake when expressed in yeast and oocytes. A double sweet13 sweet14 mutant has a defect in anther dehiscence and this phenotype can be reversed by exogenous GA treatment. In addition, sweet13 sweet14 exhibits altered long distant transport of exogenously applied GA and altered responses to GA during germination and seedling stages. These results suggest that AtSWEET13 and AtSWEET14 may be involved in modulating GA response in Arabidopsis.

Influence of chelation strength and bacterial uptake of gallium salicylidene acylhydrazide on biofilm formation and virulence of Pseudomonas aeruginosa

Development of antibiotic resistance in bacteria causes major challenges for our society and has prompted a great need for new and alternative treatment methods for infection. One promising approach is to target bacterial virulence using for example salicylidene acylhydrazides (hydrazones). Hydrazones coordinate metal ions such as Fe(III) and Ga(III) through a five-membered and a six-membered chelation ring. One suggested mode of action is via restricting bacterial Fe uptake. Thus, it was hypothesized that the chelating strength of these substances could be used to predict their biological activity on bacterial cells. This was investigated by comparing Ga chelation strength of two hydrazone complexes, as well as bacterial Ga uptake, biofilm formation, and virulence in the form of production and secretion of a toxin (ExoS) by Pseudomonas aeruginosa. Equilibrium constants for deprotonation and Ga(III) binding of the hydrazone N′-(5-chloro-2-hydroxy-3-methylbenzylidene)-2,4-dihydroxybenzhydrazide (ME0329), with anti-virulence effect against P. aeruginosa, were determined and compared to bacterial siderophores and the previously described Ga(III) 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (Ga-ME0163) and Ga-citrate complexes. In comparison with these two complexes, it was shown that the uptake of Ga(III) was higher from the Ga-ME0329 complex. The results further show that the Ga-ME0329 complex reduced ExoS expression and secretion to a higher extent than Ga-citrate, Ga-ME0163 or the non-coordinated hydrazone. However, the effect against biofilm formation by P. aeruginosa, by the ME0329 complex, was similar to Ga-citrate and lower than what has been reported for Ga-ME0163.

Lack of Increased FDG Uptake in the Lacrimal and Salivary Glands in Patients With Sarcoidosis and Potential Underlying Mechanism

Increased 67Ga uptake in the mediastinal/hilar lymph nodes ("lambda") and in the lacrimal/parotid/submandibular glands ("panda") often coexists in patients with sarcoidosis (Sarc-Pts). However, we observed that increased lacrimal/salivary uptake is uncommon on 18F-FDG PET/CT (FDG-panda) in many Sarc-Pts who showed increased mediastinal/hilar uptake (FDG-lambda). We evaluated parotid and lacrimal FDG activity in Sarc-Pts who showed FDG-lambda in comparison with a control patient group and attempted to find underlying mechanisms to explain the discrepancy between FDG and Ga uptake in these organs. Parotid FDG activity (FDG-P) was assessed visually using a 0- to 3-point scale (0 being = or minimally > background, and 3 > liver) and quantitatively using SUVmean in 52 confirmed Sarc-Pts with FDG-lambda (lambda group) as well as in 52 non-Sarc-Pts (control group). Lacrimal FDG activity (FDG-L) was assessed visually (0 being = or minimally > subcutaneous tissue, and 1 clearly > subcutaneous tissue). There was no significant difference in the parotid SUVmean between lambda (1.88 ± 0.65) and control (1.76 ± 0.62) groups (P = 0.333). Also, there was no difference in visually graded FDG-P between the 2 groups (P = 0.257). None of the patients in all groups showed apparently abnormal (grade 1) FDG-L. Increased FDG-L/FDG-P is rare in Sarc-Pts demonstrating FDG-lambda, which is strikingly different from the clinical experience as well as the reported data on Ga scintigraphy. Discrepancy in various cytokine levels between lacrimal samples and intrathoracic lesions in Sarc-Pts reported in the literature appears to correlate well with variable Ga and FDG uptake in the lacrimal gland and intrathoracic lesions.

Isolation and characterization of gallium resistant Pseudomonas aeruginosa mutants

Pseudomonas aeruginosa PA14 cells resistant to the novel antimicrobial gallium nitrate (Ga) were developed using transposon mutagenesis and by selecting spontaneous mutants. The mutants showing the highest growth in the presence of Ga were selected for further characterization. These mutants showed 4- to 12-fold higher Ga minimal inhibitory growth concentrations and a greater than 8-fold increase in the minimum biofilm eliminating Ga concentration. Both types of mutants produced Ga resistant biofilms whereas the formation of wild-type biofilms was strongly inhibited by Ga. The gene interrupted in the transposon mutant was hitA, which encodes a periplasmic iron binding protein that delivers Fe3+ to the HitB iron permease; complementation of the mutant with the hitA gene restored the Ga sensitivity. This hitA mutant showed a 14-fold decrease in Ga internalization versus the wild-type strain, indicating that the HitAB system is also involved in the Ga uptake. Ga uptake in the spontaneous mutant was also lower, although no mutations were found in the hitAB genes. Instead, this mutant harbored 64 non-silent mutations in several genes including those of the phenazine pyocyanin biosynthesis. The spontaneous mutant produced 2-fold higher pyocyanin basal levels than the wild-type; the addition of this phenazine to wild-type cultures protected them from the Ga bacteriostatic effect. The present data indicate that mutations affecting Ga transport and probably pyocyanin biosynthesis enable cells to develop resistance to Ga.

Less May Be as Good as More

We presented a patient with abnormal focal accumulation of 67Ga in the left upper abdomen. After drinking water, we successfully identified the abnormal radioactivity that was from the stomach. Subsequent endoscopic examination did not reveal gastric pathological condition. Gastric accumulation of 67Ga may relate to pathological conditions or physiological uptake, confounding interpretation of 67Ga scintigraphy. Simple water ingestion method can rapidly identify gastric 67Ga uptake, and the shape of distended stomach can also help to differentiate pathological conditions from physiological uptake, which is especially helpful for a busy nuclear medicine department and for places where the SPECT/CT systems are not available.

Supernumerary Breast Masquerading as Metastasis on Serial 67Ga Scan

We report the incidental discovery of supernumerary breast changes on sequential ⁶⁷Ga scans in a woman with dermatofibrosarcoma protuberans excised 5 years before. The appearance of the accessory breast fluctuated with physiological ⁶⁷Ga uptake of the breast tissue was evident. Awareness of the concomitant changes in accessory breast with breast tissue could help narrow the differential diagnosis.

Association between gallium-67 uptake by lung foci and sputum smear status in patients with pulmonary tuberculosis

Rapid determination of the inflammatory and sputum smear status in patients with pulmonary tuberculosis (PTB) is crucial for clinical decision making. The purpose of this study was to assess the relationship between gallium-67 (Ga-67) uptake by lung foci and sputum smear status in patients with PTB. We also attempted to predict the patients with acid-fast bacilli (AFB) smear-positive PTB by means of a semiquantitative measurement of Ga-67 uptake ratio using single-photon emission computed tomography images. Ninety-five patients with PTB were enrolled in this retrospective study. A volume-of-interest method was used to quantify Ga-67 uptake in single-photon emission computed tomography images. The Ga-67 uptake ratio was defined as the maximum voxel value of the pulmonary lesion divided by the maximum voxel value of normal lung tissue. The Ga-67 uptake ratio was higher in patients with active PTB than in those with inactive PTB (3.11 ± 1.52 vs. 1.42 ± 0.14, P<0.01). In active PTB, the Ga-67 uptake ratio was higher in smear-positive patients than in smear-negative patients (3.41 ± 1.60 vs. 2.16 ± 0.61, P<0.01). In patients with AFB smear grades 1+, 2+, and 3+, the Ga-67 uptake ratios were 2.51 ± 0.81, 3.30 ± 1.57, and 4.23 ± 1.73, respectively. The correlation between Ga-67 uptake ratio and AFB smear grading was statistically significant (Spearman's ρ=0.60, P<0.01). In receiver operating characteristic curve analyses, the area under the curve for the Ga-67 uptake ratio was 0.95 ± 0.02 (P<0.01) for predicting active PTB and 0.87 ± 0.04 (P<0.01) for predicting smear-positive active PTB. In patients with active PTB, more-intense Ga-67 uptake was associated with more AFB load in the sputum - that is a greater potential to transmit PTB. This finding might facilitate clinical decision making for immediate isolation and treatment to reduce transmission of PTB.

Abstract 17849: Additional Use of Methotrexate Improved Clinical Findings and Metabolic Profile in Patients with Cardiac Sarcoidosis Refractory to Corticosteroids

Background. Corticosteroids are indicated in cardiac sarcoidosis (CS). However, some patients worsen clinically despite corticosteroid treatment, and are suffering from steroid-related side effects. Methotrexate (MTX) is one of the most commonly used cytotoxic agents and has steroid-sparing effects for autoimmune diseases. Furthermore, aniti-inflammatory property of this agent may affect the pathogenesis of chronic heart failure. We hypothesized that MTX has a potential to improve clinical findings and reduce side effects of corticosteroids in patients with refractory CS. Methods. Out of 30 ambulatory CS patients treated with corticosteroids, we added MTX in combination with maintenance dose of corticosteroids for 7 patients who were suffering from relapse or deterioration and steroid-related side effects such as poorly controlled diabetes, osteoporosis or psychosis. All of the 7 were treated with 7.5mg of MTX once a week. A mean duration of corticosteroid treatment in the 7 patients was 61 months (32 to 95 months). Results. During a mean follow-up of 30 (12 to 46) months, no cardiac event and no major side effect occurred. The addition of MTX reduced maintenance steroid doses without further deterioration (8.3±3.4 to 6.4±2.2mg, p&lt;0.05) during the follow-up periods. Although LVEF was not significantly increased, plasma BNP level was significantly decrease from 120±106 to 75±68pg/ml (p&lt;0.05). There were significant improvements in diabetes (HbA1c:7.6±1.9 to 7.2±2.0%, p&lt;0.05) and lipid profile (Triglyceride levels: 226±124 to 167±118mg/dl, p&lt;0.05). Increased uptake of 99m Tc-sestamibi and decreased uptake of 67 Ga in the myocardium were clearly observed in 2 patients after the addition of MTX. Conclusion. MTX is safe and helpful in combination with corticosteroids improving clinical findings, allowing for lower steroid doses, and reducing side effects of corticosteroids in patients with CS.

Use of an oral effervescent agent in the evaluation of gastric 67Ga uptake

Gastric uptake of (67)Ga may be observed in patients with no obvious gastric lesions, as well as those with gastric malignancy. The aim of this study was to investigate whether the use of an effervescent agent aids in evaluating gastric (67)Ga uptake. Twenty patients having or suspected of having gastric uptake on whole-body (67)Ga scintigrams were studied. Anterior abdominal images were obtained at baseline and after the oral intake of the effervescent agent (gas contrast image). The presence or absence of malignant gastric uptake was judged visually using the baseline image or gas contrast image. The judgment was compared with the clinical diagnosis, and the clinical usefulness of the gas contrast technique was assessed. In all patients, successful distension of the stomach was indicated in the gas contrast image. Clinical assessment showed gastric lesions in six patients (gastric involvement of lymphoma in 3, primary gastric lymphoma in 2, and adenocarcinoma in 1). The gas contrast image yielded accurate judgments of malignant gastric uptake in all patients except one with adenocarcinoma. Imaging after gastric distension induced by the oral effervescent agent contributed to excluding malignant gastric uptake in eight patients and demonstrating malignant gastric uptake in four patients. Benign gastric uptake may complicate the assessment of gastric lesions in (67)Ga scintigraphy. Additional spot imaging after oral intake of an effervescent agent can aid in evaluating malignant gastric lesions through gastric distension.

67Ga Uptake in Secondary Tumoral Calcinosis

Secondary tumoral calcinosis is a rare disorder that is most prevalent in patients with chronic renal failure. It is characterized by lobular densely calcified masses confined to the soft tissue, generally at the extensor surface of a joint in the anatomic distribution of a bursa. We describe a case of a 38-y-old man undergoing dialysis who presented with pyrexia of unknown origin and raised inflammatory markers but was otherwise asymptomatic. A (67)Ga scan was performed, on which an incidental diagnosis of secondary tumoral calcinosis was made.

The role of gallium-67 scintigraphy in comparing inflammatory activity between tuberculous and nontuberculous mycobacterial pulmonary diseases

The purpose of this study was to compare the inflammatory activity of pulmonary lesions between active tuberculosis and nontuberculous mycobacterial (NTM) infection in acid-fast bacilli smear-positive non-HIV-infected patients using gallium-67 (Ga) scintigraphy. Twenty-four patients with culture-proven active pulmonary tuberculosis (PTB) and an additional 17 patients meeting the criteria of pulmonary NTM infection were enrolled into the retrospective study. The Ga uptake of the pulmonary lesion was assessed by visual scoring of uptake grade and semiquantitative region of interest analysis of the uptake ratio using the thoracic spine as a reference. Ga scans were positive in 23 of the 24 patients (95.8%) with PTB and in 12 of the 17 patients (70.6%) with pulmonary NTM infection. Twenty patients with active PTB had moderate or intense visual Ga uptake grade, whereas only three patients with pulmonary NTM infection had moderate visual Ga uptake grade. The semiquantitative pulmonary Ga uptake ratios in patients with active PTB and NTM infection were 1.17 ± 0.28 (range: 0.77-1.86) and 0.79 ± 0.12 (range: 0.60-1.03), respectively. The Ga uptake grade and ratio of active PTB were both significantly higher than NTM infection (both P < 0.001). In the receiver operating characteristic curve analysis for predicting active PTB, the area under the curves of Ga uptake grade and ratio were 0.90 ± 0.05 and 0.93 ± 0.04, respectively (both P < 0.001). The inflammatory activity of active PTB is significantly higher than that of pulmonary NTM infection in non-HIV-infected patients. Ga uptake grade and ratio could be used to predict active PTB in acid-fast bacilli smear-positive patients.

Prognostic value of dual‐time‐point 18F‐fluorodeoxyglucose positron emission tomography in patients with pulmonary sarcoidosis

The value of dual-time- point (18) F-FDG PET was investigated to predict the prognosis of patients with pulmonary sarcoidosis. Twenty-one patients with pulmonary sarcoidosis underwent (18) F-FDG PET examinations at two time points: an early scan at 60min and a delayed scan at 180min after injection of (18) F-FDG. Standardized uptake values (SUVs) at the two time points and the retention index (RI-SUV) calculated from these were evaluated. To evaluate disease progression, all patients underwent chest CT 1year after (18) F-FDG PET. Using these results, the accuracy of (18) F-FDG PET parameters and (67) Ga uptake for predicting disease persistence were compared, and the correlations between those parameters and serum markers were assessed. RI-SUV was significantly higher in patients with increased or unchanged pulmonary lesions at follow-up CT (persistent group; 21.3±9.6%) than in patients with improved pulmonary lesions (improved group; -9.2±28.6%, P=0.0075). The diagnostic accuracy of RI-SUV in the persistent group was significantly greater than that of early SUV or (67) Ga uptake, and serum soluble IL-2 receptor showed a significant correlation with RI-SUV. RI-SUV showed better diagnostic accuracy compared with early SUV or (67) Ga uptake, in patients with persistent lung involvement at 1year. It may be a useful measure of persistent inflammation in patients with pulmonary sarcoidosis.

Semiquantitative measurement of pulmonary hilar gallium-67 uptake using single photon emission computed tomography/computed tomography for the diagnosis of autoimmune pancreatitis

We ascertained the difference in the level of pulmonary hilar (PH) gallium-67 (Ga-67) uptake in autoimmune pancreatitis (AIP) patients between the active (before corticosteroid therapy) and remittent (after 4 weeks of corticosteroid therapy) phases using a semiquantitative measurement method based on single photon emission computed tomography (SPECT) with integrated low-dose computed tomography (CT). Ga-67 planar scans and SPECT were performed in 11 AIP patients before and after 4 weeks of corticosteroid therapy. A region of interest (ROI) was drawn over the bilateral pulmonary hilum and the liver, and average counts of the pulmonary hilum and liver were calculated. The average counts of the pulmonary hilum divided by those of the liver gave the pulmonary hilum/liver ratio (H/L). A significant difference was observed in the H/L between active and remittent phases. H/L in the active phase was 1.03±0.32 and that in the remittent phase was 0.58±0.25 (t-test, P=0.0016). PH Ga-67 uptake in patients with active AIP was semiquantitatively higher than that in those with remittent AIP. Hence, this may be a useful finding for an early diagnosis, estimating the effectiveness of corticosteroid therapy, and following up patients with this disease.

Unravelling the gallic acid degradation pathway in bacteria: the gal cluster from Pseudomonas putida

Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is widely distributed in nature, being a major phenolic pollutant and a commonly used antioxidant and building-block for drug development. We have characterized the first complete cluster (gal genes) responsible for growth in GA in a derivative of the model bacterium Pseudomonas putida KT2440. GalT mediates specific GA uptake and chemotaxis, and highlights the critical role of GA transport in bacterial adaptation to GA consumption. The proposed GA degradation via the central intermediate 4-oxalomesaconic acid (OMA) was revisited and all enzymes involved have been identified. Thus, GalD is the prototype of a new subfamily of isomerases that catalyses a biochemical step that remained unknown, i.e. the tautomerization of the OMAketo generated by the GalA dioxygenase to OMAenol. GalB is the founding member of a new family of zinc-containing hydratases that converts OMAenol into 4-carboxy-4-hydroxy-2-oxoadipic acid (CHA). galC encodes the aldolase catalysing CHA cleavage to pyruvic and oxaloacetic acids. The presence of homologous gal clusters outside the Pseudomonas genus sheds light on the evolution and ecology of the gal genes in GA degraders. The gal genes were used for expanding the metabolic abilities of heterologous hosts towards GA degradation, and for engineering a GA cellular biosensor.

Assessment of inflammation in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia

PurposeArrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a myocardial disease that predominantly affects the right ventricle (RV). Its hallmark feature is fibro-fatty replacement of RV myocardium. However, patchy inflammatory infiltrates in the RV are also consistently reported using autopsy and myocardial biopsy. Although the role of inflammation in ARVC/D is unresolved, the ability to assess inflammation non-invasively may aid in the diagnostic process. We aimed to establish whether cardiac inflammation can be assessed non-invasively in ARVC/D patients.MethodsIn eight ARVC/D patients and nine controls (haematology/oncology patients), the level of inflammatory activation was assessed by measuring plasma levels of inflammatory cytokines. Regional myocardial inflammation was assessed with 67Ga scintigraphy.ResultsARVC/D patients had higher plasma levels than controls of the pro-inflammatory cytokines interleukin (IL)-1β (1.22 ± 0.07 vs 0.08 ± 0.01 pg/ml, p < 0.0001), IL-6 (3.16 ± 0.44 vs 0.38 ± 0.04 pg/ml, p < 0.0001) and tumour necrosis factor (TNF)-α (9.16 ± 0.90 vs 0.40 ± 0.06 pg/ml, p < 0.0001), while levels of the anti-inflammatory cytokine IL-10 were not significantly different (1.36 ± 0.15 vs 1.20 ± 0.30 pg/ml, p = 0.74). 67Ga uptake in the RV was higher in ARVC/D patients than in controls. In ARVC/D patients, 67Ga uptake in the RV wall was higher than in the interventricular septum or left ventricular wall.ConclusionInflammation in the RV wall of ARVC/D patients can be detected non-invasively with the combined analysis of plasma levels of inflammatory cytokines and cardiac 67Ga scintigraphy.