Gallium Uptake Research Articles

PH-mediated potentiation of gallium nitrate against Pseudomonas aeruginosa.

The emergence of multidrug-resistant Pseudomonas aeruginosa isolates is a growing concern for public health, necessitating new therapeutic strategies. Gallium nitrate [Ga(NO3)3], a medication for cancer-related hypercalcemia, has attracted great attention due to its ability to inhibit P. aeruginosa growth and biofilm formation by disrupting iron metabolism. However, the antibacterial efficacy of Ga(NO3)3 is not always satisfactory. It is imperative to investigate the factors that affect the bactericidal effects of Ga(NO3)3 and to identify new ways to enhance its efficacy. This study focused on the impact of pH on P. aeruginosa resistance to Ga(NO3)3, along with the underlying mechanism. The results indicate that acidic conditions could increase the effectiveness of Ga(NO3)3 against P. aeruginosa by promoting the production of pyochelin and gallium uptake. Subsequently, using glutamic acid, a clinically compatible acidic amino acid, the pH was significantly lowered and enhanced the bactericidal and inhibitory efficacy of Ga(NO3)3 against biofilm formation by P. aeruginosa, including a reference strain PA14 and several multidrug-resistant clinical isolates. Furthermore, we used an abscess mouse model to evaluate this combination in vivo; the results show that the combination of glutamic acid and Ga(NO3)3 significantly improved P. aeruginosa clearance. Overall, the present study demonstrates that acidic conditions can increase the sensitivity of P. aeruginosa to Ga(NO3)3. Combining glutamic acid and Ga(NO3)3 is a potential strategy for the treatment of P. aeruginosa infections.

Wake biofilm up to enhance suicidal uptake of gallium for chronic lung infection treatment

The hypometabolic and nutrient-limiting condition of dormant bacteria inside biofilms reduces their susceptibility to antibacterial agents, making the treatment of biofilm-dominating chronic infections difficult. Herein, we demonstrate an intratracheal aerosolized maltohexaose-modified catalase-gallium integrated nanosystem that can ‘wake up’ dormant Pseudomonas aeruginosa biofilm to increase the metabolism and nutritional iron demand by reconciling the oxygen gradient. The activated bacteria then enhance suicidal gallium uptake since gallium acts as a 'Trojan horse' to mimic iron. The internalized gallium ions disrupt biofilms by interfering with the physiological processes of iron ion acquisition and utilization, biofilm formation, and quorum sensing. Furthermore, aerosol microsprayer administration and bacteria-specific maltohexaose modification enable accumulation at biofilm-infected lung and targeted release of gallium into bacteria to improve the therapeutic effect. This work provides a potential strategy for treating infection by reversing the dormant biofilm's resistance condition.

PET imaging of new target CDK19 in prostate cancer.

Prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) is a superior method to predict patients' risk of cancer progression and response to specific therapies. However, its performance is limited for neuroendocrine prostate cancer (NEPC) and PSMA-low prostate cancer cells, resulting in diagnostic blind spots. Hence, identifying novel specific targets is our aim for diagnosing those prostate cancers with low PSMA expression. The Cancer Genome Atlas (TCGA) database and our cohorts from men with biopsy-proven high-risk metastatic prostate cancer were used to identify CDK19 and PSMA expression. PDX lines neP-09 and P-16 primary cells were used for cellular uptake and imaging mass cytometry in vitro. To evaluate in vivo CDK19-specific uptake of gallium(Ga)-68-IRM-015-DOTA, xenograft mice models and blocking assays were used. PET/CT imaging data were obtained to estimate the absorbed dose in organs. Our study group had reported the overexpression of a novel tissue-specific gene CDK19 in high-risk metastatic prostate cancer and CDK19 expression correlated with metastatic status and tumor staging, independently with PSMA and PSA levels. Following up on this new candidate for use in diagnostics, small molecules targeting CDK19 labeled with Ga-68 (68Ga-IRM-015-DOTA) were used for PET in this study. We found that the 68Ga-IRM-015-DOTA was specificity for prostate cancer cells, but the other cancer cells also took up little 68Ga-IRM-015-DOTA. Importantly, mouse imaging data showed that the NEPC and CRPC xenografts exhibited similar signal strength with 68Ga-IRM-015-DOTA, but 68Ga-PSMA-11 only stained the CRPC xenografts. Furthermore, target specificity was elucidated by a blocking experiment on a CDK19-bearing tumor xenograft. These data concluded that 68Ga-CDK19 PET/CT was an effective technology to detect lesions with or without PSMA in vitro, in vivo, and in the PDX model. Thus, we have generated a novel PET small molecule with predictive value for prostate cancer. The findings indicate that 68Ga-CDK19 may merit further evaluation as a predictive biomarker for PET scans in prospective cohorts and may facilitate the identification of molecular types of prostate cancer independent of PSMA.

Epipericardial fat necrosis: a case report of an underdiagnosed disease.

Epipericardial fat necrosis: a case report of an underdiagnosed disease.

Usefulness of gallium-67 scintigraphy for evaluating the histopathological activity in interstitial nephritis

Interstitial nephritis is a common cause of renal failure. Gallium-67 scintigraphy is reportedly useful for diagnosing interstitial nephritis; however, its ability to assess disease activity remains unknown. We aimed to analyze the relationship between the renal uptake of gallium-67 and the disease activity in interstitial nephritis. We retrospectively analyzed the data of patients who underwent gallium-67 scintigraphy at a hospital in Tokyo. The renal uptake adjusted for the soft tissues beneath the kidneys was semi-quantitatively evaluated. We compared the renal uptake levels between patients clinically diagnosed with and without interstitial nephritis. Among those undergoing renal biopsy, we evaluated the predictive ability of gallium-67 scintigraphy and analyzed the renal uptake levels regarding the disease activity through a histopathological analysis. We included 143 patients; among them, 30, 17, and 96 patients were clinically diagnosed with interstitial nephritis, other kidney diseases, and non-kidney diseases, respectively. The renal uptake of gallium-67 was the highest among patients with interstitial nephritis. Among the 25 patients who underwent renal biopsy, 15 were pathologically diagnosed with interstitial nephritis. The renal uptake levels showed a high discriminative ability (C-statistic: 0.83). Furthermore, net reclassification improvement with the addition of gallium-67 scintigraphy to N-acetyl-β-D-glucosaminidase for the prediction of interstitial nephritis was 1.14. Histopathological analysis revealed a positive correlation between renal uptake and inflammation in the cortex and peritubular capillaries. This study confirmed the diagnostic value and potential usefulness of gallium-67 scintigraphy for evaluating interstitial nephritis.

Cardiac Metastasis of Neuroendocrine Tumor Without Cardiovascular Symptoms

A 72-year-old man with a stage IV small intestinal neuroendocrine tumor presented to our cardiology clinic as a referral for an abnormal positron emission tomography–computed tomography scan with an intense gallium uptake in the heart. Follow-up cardiac magnetic resonance was suggestive of myocardium infiltration by the neuroendocrine tumor with late gadolinium enhancement and T1 time elevation. (Level of Difficulty: Intermediate.)

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.

Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients.

Background: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. Methods: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. Results: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0–1.3), 0.95 (0.9–1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. Conclusions: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.

The growth and uptake of gallium (Ga) and indium (In) of wheat seedlings in Ga- and In-contaminated soils

The emerging contaminants gallium (Ga) and indium (In) are extensively used in advanced industries and are considered as toxic to humans. Limited information is available on the dynamics of Ga and In in soil-upland crop systems. Therefore, this study aimed to investigate the effects of Ga and In on the growth and uptake of Ga and In by wheat plants grown in Ga- and In-contaminated soils. The wheat seedlings were planted in soils of different properties spiked with various Ga and In concentrations (50, 100, 200, and 400 mg kg−1). The plant-available Ga, In, and Al in the soils were extracted by 0.02 M CaCl2, and their concentrations in plant tissues of wheat seedlings and plant biomass were determined after harvesting. The results indicated that the Al toxicity of wheat seedlings increased with Ga and In concentrations in acidic soils. Indium phytotoxicity was found in both neutral and acidic soils. Plant analysis results indicated that the concentration of Ga and In in roots was approximately one order of magnitude higher than that in the shoots of wheat seedlings, and the capability for Ga translocation from roots to shoots was higher than for In. The results of this study suggest that the dynamics of Ga and In in soil-upland crop systems is strongly dependent on the soil properties, such as pH and Al availability.

Invited Commentary: Radiogenomics Applied to Select Abdominal Tumors.

Invited Commentary: Radiogenomics Applied to Select Abdominal Tumors.

The mobility and plant uptake of gallium and indium, two emerging contaminants associated with electronic waste and other sources

Gallium (Ga) and indium (In) are increasingly susceptible to soil contamination via disposal of electronic equipment. Chemically similar to aluminium (Al), these elements may be mobile and bioavailable under acidic conditions. We sought to determine extent and nature of Ga and In mobility in the soil – plant system and thus their potential to enter the food chain. Batch sorption experiments on a high fertility silt loam (pH 5.95, CEC 22 meq 100 g−1) showed strong retention of both elements to the soil matrix, with mean distribution coefficient (KD) values of 408 and 2021 L kg−1 for Ga and In respectively. KD increased with concentration, which we attributed to precipitation of excess ions as insoluble hydroxides. KD decreased with increased pH as Ga/In(OH)2+ and Ga/In(OH)2+ transitioned to Ga/In(OH)4-. Movement into the aboveground portions of perennial ryegrass (Lolium perenne L.) was low, with bioaccumulation factors of 0.0037 for Ga and 0.0002 for In; foliar concentrations peaked at 11.6 mg kg−1 and 0.015 mg kg−1 respectively. The mobility of Ga and In in the soil - plant system is low compared to other common trace element contaminants such as cadmium, copper, and zinc. Therefore, Ga and In are likely to accumulate in soils and soil ingestion, either directly, via inhaled dust, or dust attached to food, will be the largest pathway into the food chain. Future work should focus on the effect of redox conditions on Ga and In, as well as uptake into acidophilic plants such as Camellia spp., which accumulate Al.

Salivary Gland Scintigraphy in Patients with Sjogren's Syndrome: A local Experience with Dual-tracer.

Objective(s):To review the findings of the patients with Sjögren’s syndrome (SS) having technetium99-m-pertechnetate (99mTc-pertechnetate) and gallium67- citrate (Ga-67) salivary gland scintigraphy in the past eight years.Methods:The patients with SS, who were referred to our department for salivary gland scintigraphy during January -2008December 2015 were studied using both 99mTc-pertechnetate and Ga-67 citrate scintigraphy.Results:Eighteen patients were included in the study, 17 of whom had positive findings on 99mTc-pertechnetate salivary gland scintigraphy. One patient had negative parotid glands findings on 99mTc-pertechnetate, but positive findings in Ga-67 study. Four patients had asymmetric involvement of the parotid glands, and one patient had asymmetric involvement of the submandibular glands in 99mTc-pertechnetate salivary gland scintigraphy. On the other hand, one patient had only submandibular gland involvement in the 99mTc-pertechnetate scan. Nine patients (18/9) had positive parotid gland findings on Ga-67 study. The involvements of the parotid glands were all symmetrical, except for one patient. No abnormal gallium uptake in the submandibular glands in our patients was noted.Conclusion:99mTc-pertechnetate salivary gland scintigraphy is sufficient for the assessment in the majority of patients with SS. Ga-67 scintigraphy may be a useful supplementary test, especially if the result of 99mTc-pertechnetate scintigraphy is not conclusive.

Usefulness of 18F-Fluorodeoxyglucose-position emission tomography with computed tomography and gallium-67 scintigraphy for detection of Kaposi sarcoma lesions in a 40-year-old Japanese man with AIDS

A 40-year-old Japanese man with acquired immunodeficiency syndrome was diagnosed with Kaposi sarcoma (KS) on the basis of the results of skin lesion biopsies. In addition, 18F-fluorodeoxyglucose-position emission tomography–computed tomography revealed abnormal fluorodeoxyglucose uptake in KS lesions, whereas gallium-67 scintigraphy did not show uptake of gallium. These findings indicate that combining these imaging modalities can help distinguish KS from other malignancies and opportunistic infections.

Incidence of gallium-67 citrate uptake in brown adipose tissue in neonates

Aims: Increased 18F-fluorodeoxyglucose uptake within active brown adipose tissue (BAT) on an 18F-fluorodeoxyglucose PET/CT study is a known pitfall that has been well described in the literature. We have noted a similar phenomenon occurring in gallium-67 studies performed on neonates, which introduces an undesirable element of complexity when evaluating for the presence of infection or malignancy. Since the incidence of gallium-67 uptake in BAT in neonates has not been previously described in the literature, the goal of this study was to evaluate the pattern of uptake and its incidence in our neonatal patient population. Materials & methods: A complete review was performed of the Hospital Ste-Justine's (QC, Canada) database of nuclear medicine studies carried out from June 2001 to May 2011, revealing 64 total body gallium-67 scans of neonates (carried out within the first 28 days after birth). These studies were reviewed for BAT gallium-67 uptake. Results: Ten of out 64 patients had gallium-67 uptake in a...

A Case of Chronic Lupus Myocarditis

A 49-year old woman with a 20-year history of systemic lupus erythematosus (SLE) was admitted to our hospital with progressive exertional dyspnea despite of a maintenance dose of methylprednisolon. Her left ventricular ejection fraction (LVEF) was 37% by echocardiography, late gadolinium enhancement was detected by cardiac MRI in septal and posterior wall of the left ventricle, where gallium uptake was also apparent. An elevation of cardiac troponin T (cTnT), a decrease of C3, and mild thrombocytopenia suggested SLE flare, therefore endomyocardial biopsy was performed and infiltration of monocytes with defluxion of myocytes was revealed.

Lacrimal Gland Uptake of 67Ga-gallium Citrate Correlates with Biopsy Results in Patients with Suspected Sarcoidosis

Purpose: To investigate whether lacrimal gland uptake on 67Ga-gallium citrate scintigraphy correlates with histopathologic evidence of sarcoidosis.Methods: A retrospective, pilot study of 31 patients with suspected sarcoidosis who underwent gallium scintigraphy and lacrimal gland biopsy. Lacrimal gland gallium uptake was assessed by subjective visual scoring (SVS) and lacrimal uptake ratio (LUR).Results: Eleven (36%) patients had lacrimal gland biopsies containing noncaseating granulomas. A statistically significant correlation was found between lacrimal gland gallium uptake and biopsy positivity using SVS (p = 0.03) or LUR (p = 0.01). Using SVS, biopsy positivity rate increased from 0 to 50% in patients with mild to intense uptake. Using LUR, biopsy positivity rate increased linearly as the ratio increased from 13% (LUR < 4) to 100% (LUR > 8).Conclusions: Lacrimal biopsy positivity rate significantly correlated with gallium uptake on scintigraphy. Both SVS and LUR methods appear to correlate with histologic results and may potentially aid in patient selection for biopsy.

Erythropoietin-producing tubercle granuloma in a hemodialysis patient

BackgroundWe describe a case of a fever of unknown etiology that was caused by a caseating tubercle granuloma which produced erythropoietin. To our knowledge, this is the first report of an erythropoietin- producing granuloma.Case presentationA 48-year-old Japanese man with a 5-year history of maintenance hemodialysis for diabetic nephropathy presented with an intermittent fever over a few months. During febrile periods he developed erythema nodosum on his legs. Computed tomography showed axillary lymph node enlargement and this was further corroborated by a gallium scan that revealed high gallium uptake in these nodes. A Mantoux test was positive and an interferongamma release assay for tuberculosis diagnosis was also positive. Lymph node tuberculosis was suspected and the patient underwent lymphadenectomy. Histological analysis of the lymph nodes revealed a caseating granuloma that showed positive results on an acid-fast bacteria stain and a Mycobacterium tuberculosis polymerase chain reaction test. After lymphadenectomy, however, the patient’s hemoglobin levels rapidly decreased from 144 to 105 g/L, and this was further compounded by a decrease in serum erythropoietin from 223 mIU/mL to 10.7 mIU/mL by postoperative day 21. We suspected the tubercle to be a source of the erythropoietin and this was further confirmed by in situ hybridization.ConclusionsWe report for the first time ectopic erythropoietin production by a tuberculous lymph node. Our observations are substantiated by a postoperative decline in his erythropoietin level and a clinical requirement for erythropoietin treatment.

Poster Abstracts

Poster Abstracts

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.

Fever of unknown origin (FUO) due to large B-cell lymphoma: The diagnostic significance of highly elevated alkaline phosphatase and serum ferritin levels

BackgroundDetermining the cause of fever of unknown origin (FUO) is often a vexing and difficult diagnostic process. In most cases, the signs and symptoms in adult FUOs suggest a malignant, infectious, or rheumatic/inflammatory etiology. The diagnosis of FUO may be narrowed if specific findings are present (eg, hepatosplenomegaly) that limit the diagnostic possibilities. Infectious causes of FUO with hepatosplenomegaly include miliary tuberculosis, typhoid fever, and visceral leishmanosis (kala-azar). However, FUOs with hepatosplenomegaly are most often attributable to malignant neoplasms, ie, Hodgkin lymphoma, non-Hodgkin lymphoma, hepatoma, hypernephroma (renal-cell carcinoma), or preleukemia. Methods and ResultsWe present a middle-aged woman with FUO and hepatosplenomegaly. Inpatient nonspecific laboratory findings included a highly elevated erythrocyte sedimentation rate, and elevated levels of vitamin B12, lactate dehydrogenase, angiotensin-converting enzyme, ferritin, and alkaline phosphatase. These individual findings are nonspecific, but together point to a lymphoma. An important test in differentiating malignant from infectious FUOs is the Naprosyn test, and her Naprosyn test was positive, indicating malignancy. A gallium scan suggested a uterine lymphoma. A computed tomography scan revealed hepatosplenomegaly, but the gallium uptake was not increased in her liver and spleen. Uterine and bone marrow biopsies were negative for lymphoma. ConclusionWe present a case of FUO with hepatosplenomegaly attributable to large B-cell lymphoma as diagnosed via liver biopsy.