Radionuclide Imaging of Fungal Infections and Correlation with the Host Defense Response

The human response to invading fungi includes a series of events that detect, kill, or clear the fungi. If the metabolic host response is unable to eliminate the fungi, an infection ensues. Some of the host response's metabolic events to fungi can be imaged with molecules labelled with radionuclides. Several important clinical applications have been found with radiolabelled biomolecules of inflammation. 18F-fluorodeoxyglucose is the tracer that has been most widely investigated in the host defence of fungi. This tracer has added value in the early detection of infection, in staging and visualising dissemination of infection, and in monitoring antifungal treatment. Radiolabelled antimicrobial peptides showed promising results, but large prospective studies in fungal infection are lacking. Other tracers have also been used in imaging events of the host response, such as the migration of white blood cells at sites of infection, nutritional immunity in iron metabolism, and radiolabelled monoclonal antibodies. Many tracers are still at the preclinical stage. Some tracers require further studies before translation into clinical use. The application of therapeutic radionuclides offers a very promising clinical application of these tracers in managing drug-resistant fungi

Association between plasma homocysteine and myocardial SPECT abnormalities in patients referred for suspected myocardial ischaemia

BACKGROUND: Elevated plasma homocysteine level has emerged as a relatively newly recognised risk factor for coronary artery disease (CAD). However, reduction of plasma homocysteine levels in large prospective studies did not appear to reduce the risk for subsequent cardiac events. In this study, we investigated the association between plasma homocysteine levels and quantitative indices of myocardial perfusion SPECT imaging in patients referred for myocardial ischaemia. METHODS: Quantitative myocardial perfusion SPECT indices were obtained for 120 patients who were recruited for the study. All patients underwent a two-day rest-stress myocardial perfusion imaging. Plasma venous sampling was done on all patients after an overnight fast. Of the 120 participants (mean age 56 years, 53% males), 33% had elevated plasma homocysteine levels. The plasma homocysteine level was then compared to the results of imaging and other known risk factors. RESULTS: After adjustment for traditional risk factors of coronary artery disease, patients with elevated homocysteine levels had a significantly higher mean summed stress score (SSS) (11.3 vs 6.9, p = 0.02) than patients with a normal homocysteine level. This was true for both single- and multi-vessel disease. Also, patients with elevated homocysteine levels had a higher stress end-systolic volume (SESV) (137 vs 105 ml, p = 0.03) and lower post-stress left ventricular ejection fraction (SEF) (54 vs 64%, p = 0.02). The patients with elevated plasma homocysteine levels also had a significantly lower mean body mass index (BMI) (26.6 vs 30.6 kg/m2, p = 0.002). There was a significant relationship between the total number of known risk factors in a patient with CAD and the proportion of patients presenting with elevated plasma homocysteine levels (p = 0.03). Also, the extent of infarct, as measured by the summed rest score (SRS), was more closely correlated with an elevated homocysteine level than with the degree of ischaemia. CONCLUSION: There was a correlation between plasma homocysteine level and the presence and extent of myocardial perfusion abnormalities in patients with established coronary artery disease, in particular those with multiple risk factors and multi-vessel infarction.http://www.cvjsa.co.z

Monitoring Response to Therapy

Monitoring response to treatment is a key element in the management of infectious diseases, yet controversies still persist on reliable biomarkers for noninvasive response evaluation. Considering the limitations of invasiveness of most diagnostic procedures and the issue of expression heterogeneity of pathology, molecular imaging is better able to assay in vivo biologic processes noninvasively and quantitatively. The usefulness of F-18-FDG-PET/CT in assessing treatment response in infectious diseases is more promising than for conventional imaging. However, there are currently no clinical criteria or recommended imaging modalities to objectively evaluate the effectiveness of antimicrobial treatment. Therapeutic effectiveness is currently gauged by the patient's subjective clinical response. In this review, we present the current studies for monitoring treatment response, with a focus on Mycobacterium tuberculosis, as it remains a major worldwide cause of morbidity and mortality. The role of molecular imaging in monitoring other infections including spondylodiscitis, infected prosthetic vascular grafts, invasive fungal infections, and a parasitic disease is highlighted. The role of functional imaging in monitoring lipodystrophy associated with highly active antiretroviral therapy for human immunodeficiency virus is considered. We also discuss the key challenges and emerging data in optimizing noninvasive response evaluation. (C) 2017 Elsevier Inc. All rights reserved

Impact of optimized PET imaging conditions on F-18-FDG uptake quantification in patients with apparently normal aortas

Background The cardiovascular committee of the European Association of Nuclear Medicine (EANM) recently published recommendations on imaging conditions to be observed during F-18-FDG PET imaging of vascular inflammation. This study aimed to evaluate the impact of applying these optimized imaging conditions on PET quantification of arterial F-18-FDG uptake. Methods and Results Fifty-seven patients were prospectively recruited to undergo an early F-18-FDG PET/CT imaging at 60 minutes and repeat delayed imaging at >= 120 minutes post tracer injection. Routine oncologic F-18-FDG PET protocol was observed for early imaging, while delayed imaging parameters were optimized for vascular inflammation imaging as recommended by the EANM. Aortic SUVmax of the ascending aorta and SUVmean from the lumen of the superior vena cava (SVC SUVmean) were obtained on early and delayed imaging. Target-to-background ratio (TBR) was obtained for the early and delayed imaging. Aortic SUVmax increased by a mean of 70%, while SVC SUVmean decreased by a mean of 52% between early and delayed imaging (P 180 minutes. Aortic SUVmax significantly increased at imaging time-points between 120 and 180 minutes. No significant improvement in aortic SUVmax was seen at imaging time-points beyond 180 minutes. Conclusions F-18-FDG PET imaging conditions optimized for vascular inflammation imaging lead to an improved quantification through an increase in the quantified vascular tracer uptake and decrease in blood-pool background activity

The adjunctive use of carbimazole during radioactive iodine treatment reduces the cure rate of Graves’ disease

BACKGROUND : Radioactive iodine (RAI) is widely used in the treatment of hyperthyroidism. Adjunctive antithyroid drugs (ATDs) are commonly prescribed to treat the hyperthyroid state before the RAI has taken effect. However, there is no consensus on the use of or timing of adjunctive ATD treatment with RAI. OBJECTIVES : To determine the influence of the ATD carbimazole on the cure rate of RAI treatment for Graves’ disease. METHODS: A retrospective chart review was conducted in the Department of Nuclear Medicine of the Steve Biko Academic Hospital in Pretoria. The cure rate of patients treated with RAI for Graves’ disease was analysed. The effect of adjunctive carbimazole treatment with regard to its use and timing with RAI dosing was analysed. The cure rate was determined in patients treated with carbimazole either before RAI or before and after RAI administration. Cure rate was defined by the biochemical thyroid function status (thyroxine (T4), thyroidstimulating hormone (TSH)) as euthyroid or hypothyroid from 3 months and sustained at 12 months. The need for a second dose of RAI was recorded. RESULTS : RAI treatment was administered to 171 patients with Graves’ disease. The cure rate was higher in patients receiving a higher dose of RAI. The overall cure rate increased progressively from 3 months and was 91% at 12 months. The cure rate in 97 patients not receiving carbimazole was 98%. The cure rate of the 27 patients on carbimazole treatment given before RAI administration was 81%, and 73% in the 37 patients in whom it was resumed after RAI administration. The overall cure rate was lower in patients who received carbimazole (p<0.001), but especially in patients in whom carbimazole was continued after RAI administration (p<0.001). CONCLUSIONS : Adjunctive carbimazole treatment decreased the RAI cure rate of Graves’ disease significantly.http://www.samj.org.zadm2022Nuclear MedicineSurger

Imaging fungal infections in children

Fungal infections in children rarely occur, but continue to have a high morbidity and mortality despite the development of newer antifungal agents. It is essential for these infections to be diagnosed at the earliest possible stage so appropriate treatment can be initiated promptly. The addition of high-resolution computer tomography (HR CT) has helped in early diagnosis making; however, it lacks both sensitivity and specificity. Metabolic changes precede anatomical changes and hybrid imaging with positron emission tomography (PET) integrated with imaging modalities with high anatomical resolution such as CT or magnetic resonance imaging (MRI) is likely to detect these infections at an earlier stage with higher diagnostic accuracy rates. Several authors presented papers highlighting the advantages of PET/CT in imaging fungal infections. These papers, however, usually involve a limited number of patients and mostly adults. Fungal infections behave different in children than in adults, since there are differences in epidemiology, imaging findings, and response to treatment with antifungal drugs. This paper reviews the literature and explores the use of hybrid imaging for diagnosis and therapy decision making in children with fungal infections

Radionuclide Imaging of Invasive Fungal Disease in Immunocompromised Hosts

Invasive fungal disease (IFD) leads to increased mortality, morbidity, and costs of treatment in patients with immunosuppressive conditions. The definitive diagnosis of IFD relies on the isolation of the causative fungal agents through microscopy, culture, or nucleic acid testing in tissue samples obtained from the sites of the disease. Biopsy is not always feasible or safe to be undertaken in immunocompromised hosts at risk of IFD. Noninvasive diagnostic techniques are, therefore, needed for the diagnosis and treatment response assessment of IFD. The available techniques that identify fungal-specific antigens in biological samples for diagnosing IFD have variable sensitivity and specificity. They also have limited utility in response assessment. Imaging has, therefore, been applied for the noninvasive detection of IFD. Morphologic imaging with computed tomography (CT) and magnetic resonance imaging (MRI) is the most applied technique. These techniques are neither sufficiently sensitive nor specific for the early diagnosis of IFD. Morphologic changes evaluated by CT and MRI occur later in the disease course and during recovery after successful treatment. These modalities may, therefore, not be ideal for early diagnosis and early response to therapy determination. Radionuclide imaging allows for targeting the host response to pathogenic fungi or specific structures of the pathogen itself. This makes radionuclide imaging techniques suitable for the early diagnosis and treatment response assessment of IFD. In this review, we aimed to discuss the interplay of host immunity, immunosuppression, and the occurrence of IFD. We also discuss the currently available radionuclide probes that have been evaluated in preclinical and clinical studies for their ability to detect IFD.</p

Prognostic value of 11C-methionine volume-based PET parameters in IDH wild type glioblastoma

PURPOSE: (11)C-Methionine ((11)C-MET) PET prognostication of isocitrate dehydrogenase (IDH) wild type glioblastomas is inadequate as conventional parameters such as standardized uptake value (SUV) do not adequately reflect tumor heterogeneity. We retrospectively evaluated whether volume-based parameters such as metabolic tumor volume (MTV) and total lesion methionine metabolism (TLMM) outperformed SUV for survival correlation in patients with IDH wild type glioblastomas. METHODS: Thirteen IDH wild type glioblastoma patients underwent preoperative (11)C-MET PET. Both SUV-based parameters and volume-based parameters were calculated for each lesion. Kaplan-Meier curves with log-rank testing and Cox regression analysis were used for correlation between PET parameters and overall survival. RESULTS: Median overall survival for the entire cohort was 393 days. MTV (HR 1.136, p = 0.007) and TLMM (HR 1.022, p = 0.030) were inversely correlated with overall survival. SUV-based (11)C-MET PET parameters did not show a correlation with survival. In a paired analysis with other clinical parameters including age and radiotherapy dose, MTV and TLMM were found to be independent factors. CONCLUSIONS: MTV and TLMM, and not SUV, significantly correlate with overall survival in patients with IDH wild type glioblastomas. The incorporation of volume-based (11)C-MET PET parameters may lead to a better outcome prediction for this heterogeneous patient population

FDG PET/CT for evaluating systemic arterial inflammation induced by anthracycline-based chemotherapy of Hodgkin lymphoma : a retrospective cohort study

To evaluate arterial fluorodeoxyglucose (FDG) uptake as a marker of arterial inflammation in multiple vascular beds in patients treated with anthracycline-based chemotherapy for Hodgkin lymphoma (HL). We used maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) to quantify arterial FDG uptake in the carotid artery, ascending aorta, abdominal aorta, and femoral artery obtained on positron emission tomography/computed tomography (PET/CT) imaging performed at baseline before chemotherapy and after completion of chemotherapy in patients with HL treated with an anthracycline-containing regimen. We compared the SUVmax and TBR obtained at baseline with that obtained postchemotherapy for each arterial bed to evaluate the effect of anthracycline-based chemotherapy. We evaluated the effect of cardiovascular risk factors such as human immunodeficiency virus (HIV) infection, smoking, hypertension, and diabetes on the changes in SUVmax and TBR seen in the different arterial beds after anthracycline-based chemotherapy. Fifty-two patients were included with a mean age of 34.56±10.19 years. There were 33 males, and 18 patients were HIV-infected. The mean interval between completion of chemotherapy and follow-up flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan was 65 weeks. We found no significant difference in arterial FDG uptake measured by SUVmax and TBR in all arterial beds between the pre- and post-chemotherapy FDG PET/CT. There was no significant impact of HIV infection, smoking, and hypertension on the changes in arterial FDG uptake following treatment with anthracyclinebased chemotherapy. In patients with HL who were treated with anthracycline-based chemotherapy, we found no significant increase in arterial inflammation measured by FDG PET/CT after an average follow-up period of about 65 weeks since completion of chemotherapy.https://journals.lww.com/md-journal/pages/default.aspxam2021Nuclear Medicin