The Theranostic Optimization of PSMA-GCK01 Does Not Compromise the Imaging Characteristics of [99mTc]Tc-PSMA-GCK01 Compared to Dedicated Diagnostic [99mTc]Tc-EDDA/HYNIC-iPSMA in Prostate Cancer.

PURPOSE: Radiolabeled PSMA-ligands play a major role in today's nuclear medicine. Since approval of [177Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with 99mTc or therapeutically with 188Re with both nuclides available from well-known generator systems. This novel tracer might aid to overcome aforementioned supply limitations. In this investigation, the biodistribution and general imaging characteristics of [99mTc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA in patients with advanced stage prostate cancer. In addition, the binding of both ligands to PSMA was analyzed at the molecular level using molecular docking. PROCEDURES: Two cohorts (n = 19 vs. n = 21) of patients with metastatic castration-resistant prostate cancer matched for age, tumor stage, and Gleason score underwent a planar gamma camera imaging with [99mTc]Tc-EDDA/HYNIC-iPSMA or [99mTc]Tc-PSMA-GCK01 prior to PSMA-ligand therapy for PSMA-phenotyping. The imaging data were retrospective analyzed for salivary gland, kidney, liver, soft tissue, and tumor uptake on a semi-automated ROI-analysis using HERMES Medical Solutions AB (HMS, Sweden). RESULTS: The data sets were semi-automated quantified on a ROI-based analysis. The tumor-to-background presented equal results of [99mTc]Tc-PSMA-GCK01 compared to [99mTc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [99mTc]Tc-PSMA-GCK01 vs. median 9.11 [99mTc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [99mTc]Tc-PSMA-GCK01 (0.83) compared to [99mTc]Tc-EDDA/HYNIC-iPSMA (0.55) with no statistical significance. This is in agreement with the results from the docking study revealing only a minor difference in the docking scores for both ligands. CONCLUSIONS: The novel theranostic tracer [99mTc]Tc/[188Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA. These results pave the way for the PSMA-targeting imaging and theranostic agents for a broader, rather low-cost, generator applied radio-ligand therapy utilization.

Imaging of Invasive Fungal Infections- The Role of PET/CT.

Over the last decades, the population at risk for invasive fungal disease (IFD) has increased because of medical therapy advances and diseases compromising patients' immune systems. The high morbidity and mortality associated with invasive fungal disease in the immunocompromised present the challenge of early diagnosis of the IFD and the need to closely monitor the infection during treatment. The definitive diagnosis of invasive fungal disease based on culture or histopathological methods often has reduced diagnostic accuracy in the immunocompromised and may be very invasive. Less invasive and indirect evidence of the fungal infection by serology and imaging has been used for the early diagnosis of fungal infection before definitive results are available or when the definitive methods of diagnosis are suboptimal. Imaging in invasive fungal disease is a non-invasive biomarker that helps in the early diagnosis of invasive fungal disease but helps follow-up the infection during treatment. Different imaging modalities are used in the workup to evaluate fungal disease. The different imaging modalities have advantages and disadvantages at different sites in the body and may complement each other in the management of IFD. Positron emission tomography integrated with computed tomography with [18F]Fluorodeoxyglucose (FDG PET/CT) has helped manage IFD. The combined functional data from PET and anatomical data from the CT from almost the whole body allows noninvasive evaluation of IFD and provides a semiquantitative means of assessing therapy. FDG PET/CT adds value to anatomic-based only imaging modalities. The nonspecificity of FDG uptake has led to the evaluation of other tracers in the assessment of IFD. However, these are mainly still at the preclinical level and are yet to be translated to humans. FDG PET/CT remains the most widely evaluated radionuclide-based imaging modality in IFD management. The limitations of FDG PET/CT must be well understood, and more extensive prospective studies in uniform populations are needed to validate its role in the management of IFD that can be international guidelines.

Molecular Imaging of Tuberculosis.

Despite the introduction of many novel diagnostic techniques and newer treatment agents, tuberculosis (TB) remains a major cause of death from an infectious disease worldwide. With about a quarter of humanity harboring Mycobacterium tuberculosis, the causative agent of TB, the current efforts geared towards reducing the scourge due to TB must be sustained. At the same time, newer alternative modalities for diagnosis and treatment response assessment are considered. Molecular imaging entails the use of radioactive probes that exploit molecular targets expressed by microbes or human cells for imaging using hybrid scanners that provide both anatomic and functional features of the disease being imaged. Fluorine-18 fluorodeoxyglucose (FDG) is the most investigated radioactive probe for TB imaging in research and clinical practice. When imaged with positron emission tomography interphase with computed tomography (PET/CT), FDG PET/CT performs better than sputum conversion for predicting treatment outcome. At the end of treatment, FDG PET/CT has demonstrated the unique ability to identify a subset of patients declared cured based on the current standard of care but who still harbor live bacilli capable of causing disease relapse after therapy discontinuation. Our understanding of the pathogenesis and evolution of TB has improved significantly in the last decade, owing to the introduction of FDG PET/CT in TB research. FDG is a non-specific probe as it targets the host inflammatory response to Mycobacterium tuberculosis, which is not specifically different in TB compared with other infectious conditions. Ongoing efforts are geared towards evaluating the utility of newer probes targeting different components of the TB granuloma, the hallmark of TB lesions, including hypoxia, neovascularization, and fibrosis, in TB management. The most exciting category of non-FDG PET probes developed for molecular imaging of TB appears to be radiolabeled anti-tuberculous drugs for use in studying the pharmacokinetic characteristics of the drugs. This allows for the non-invasive study of drug kinetics in different body compartments concurrently, providing an insight into the spatial heterogeneity of drug exposure in different TB lesions. The ability to repeat molecular imaging using radiolabeled anti-tuberculous agents also offers an opportunity to study the temporal changes in drug kinetics within the different lesions during treatment.

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

PURPOSE: 11C-Methionine (11C-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 11C-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 11C-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 11C-MET PET parameters may lead to a better outcome prediction for this heterogeneous patient population.

18F-FDG-PET/CT imaging of uterine cervical cancer recurrence in women with and without HIV infection.

BACKGROUND: To compare the rate, time and, pattern of recurrence of cervical cancer between patients with and without HIV infection and to determine factors predicting cervical cancer recurrence in patients evaluated by 18F-FDG-PET/CT. METHODS: We reviewed the 18F-FDG-PET/CT images of patients with histologically proven cervical carcinoma who were presenting with suspected recurrence. We extracted epidemiologic data, previous treatment, histologic subtype, HIV status, viral load and CD4 counts from the electronic laboratory database and the referral form for the 18F-FDG-PET/CT study. RESULTS: We studied 303 women including 112 HIV-infected patients. FIGO stage III disease was present in 131 patients. Of 198 patients with recurrence, 74 were HIV-infected while 124 were not (P=0.849). HIV infected patients were younger (41.99±9.30 years) compared to HIV-uninfected (50.19±11.09), P<0.001. Local recurrence was present in 125 patients while 100 patients had a distant recurrence. Recurrence occurred at a single site in 88 patients and two or more sites in 110 patients. No significant difference in the recurrent patterns between HIV-infected and uninfected patients. Median time to recurrence was 10.50 months (range: 6.00-156.00) among HIV-infected versus 12.00 months (IQR:7.00-312.00) among the uninfected, P=0.065. FIGO stage III (P=0.042) and the presence of histological sub-types other than SCC (P=0.005) were significant predictors of recurrence. HIV infection by itself was not significant in predicting recurrence (P=0.843). CONCLUSIONS: HIV infection has no significant impact on the rate, time or pattern of recurrence in women with suspected cervical carcinoma recurrence. Advanced disease and histological variant other than SCC are predictive of recurrence.

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.

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.

The Added Value of [18F]FDG PET/CT in the Management of Invasive Fungal Infections.

Anatomy-based imaging methods are the usual imaging methods used in assessing invasive fungal infections (IFIs). [18F]FDG PET/CT has also been used in the evaluation of IFIs. We assessed the added value of [18F]FDG PET/CT when added to the most frequently used anatomy-based studies in the evaluation of IFIs. The study was conducted in two University Medical Centers in the Netherlands. Reports of [18F]FDG PET/CT and anatomy-based imaging performed within two weeks of the [18F]FDG PET/CT scan were retrieved, and the presence and sites of IFI lesions were documented for each procedure. We included 155 [18F]FDG PET/CT scans performed in 73 patients. A total of 216 anatomy-based studies including 80 chest X-rays, 89 computed tomography studies, 14 magnetic resonance imaging studies, and 33 ultrasound imaging studies were studied. The anatomy-based studies were concordant with the [18F]FDG PET/CT for 94.4% of the scans performed. [18F]FDG PET/CT detected IFI lesions outside of the areas imaged by the anatomy-based studies in 48.6% of the scans. In 74% of the patients, [18F]FDG PET/CT added value in the management of the IFIs.

Impact of optimized PET imaging conditions on 18F-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 18F-FDG PET imaging of vascular inflammation. This study aimed to evaluate the impact of applying these optimized imaging conditions on PET quantification of arterial 18F-FDG uptake. METHODS AND RESULTS: Fifty-seven patients were prospectively recruited to undergo an early 18F-FDG PET/CT imaging at 60 minutes and repeat delayed imaging at ≥ 120 minutes post tracer injection. Routine oncologic 18F-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 < 0.001). TBR increased by 122% following delayed imaging. TBR increased, while SVC SUVmean declined across all time-points from 120 to > 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: 18F-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.

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 post-chemotherapy 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 ±â€Š10.19 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 anthracycline-based 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.

Comparison of Fluorine(18)-fluorodeoxyglucose and Gallium(68)-citrate PET/CT in patients with tuberculosis.

18F-FDG and 68Ga-citrate PET/CT have both been shown to be useful in the management of tuberculosis (TB). We compared the abnormal PET findings of 18F-FDG- and 68Ga-citrate-PET/CT in patients with TB. METHODS: Patients with TB on anti-TB therapy were included. Patients had a set of PET scans consisting of both 18F-FDG and 68Ga-citrate. Abnormal lesions were identified, and the two sets of scans were compared. The scan findings were correlated to the clinical data as provided by the attending physician. RESULTS: 46 PET/CT scans were performed in 18 patients, 11 (61 %) were female, and the mean age was 35.7 ± 13.5 years. Five patients also had both studies for follow-up reasons during the use of anti-TB therapy. Thirteen patients were co-infected with HIV. 18F-FDG detected more lesions than 68Ga-citrate (261 vs. 166, p < 0.0001). 68Ga-citrate showed a better definition of intracerebral lesions due to the absence of tracer uptake in the brain. The mean SUVmax was higher for 18F-FDG compared to 68Ga-citrate (5.73 vs. 3.01, p < 0.0001). We found a significant correlation between the SUVmax of lesions that were determined by both tracers (r = 0.4968, p < 0.0001). CONCLUSION: Preliminary data shows 18F-FDG-PET detects more abnormal lesions in TB compared to 68Ga-citrate. However, 68Ga-citrate has better lesion definition in the brain and is therefore especially useful when intracranial TB is suspected.

Fluorodeoxyglucose Positron Emission Tomography integrated with computed tomography in carcinoma of the cervix: Its impact on accurate staging and the predictive role of its metabolic parameters.

OBJECTIVES: To determine the impact of FDG-PET/CT in the initial staging of cervical cancer among women with and without HIV and to determine the abilities of FDG-PET/CT metabolic parameters in predicting the presence of distant metastasis. METHODS: We reviewed the FDG-PET/CT images of women with FIGO stage IB2 to IVA carcinoma of the cervix. We compared the FIGO stage before and after FDG-PET/CT. Maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion were determined. We compared these parameters between the HIV-infected and uninfected woman and also determined their abilities to predict the presence of distant metastasis. RESULTS: 126 women, mean age 48.05 ± 11.80 years were studied. Seventy-three patients were HIV-infected. The disease was upstaged in 65 patients, 32 of which were upstaged to stage IVB. HIV-infected women were younger (43.36 ± 8.03 years versus 54.51 ± 13.12, p<0.001) and had more advanced disease (p = 0.022) compared with HIV-uninfected. In a univariate logistic regression adjusted for the FIGO stage of the disease, there were significant associations between MTV and TLG of the primary tumor and distant metastasis. SUVmax, SUVmean, MTV and TLG performed well in predicting the presence of distant metastasis with areas under the curves (AUCs) of 0.63, 0.66, 0.80 and 0.77 respectively. These performances improved after adjustment for the FIGO stage of the disease with AUCs of 0.80, 0.79, 0.84 and 0.82 for SUVmax, SUVmean, MTV and TLG respectively. CONCLUSION: Inclusion of 18F-FDG-PET/CT in the pre-therapy assessment of cervical cancer improves the accuracy of staging in about half of the patients. The metabolic parameters of the primary tumor perform well in predicting the presence of distant metastases.

Diagnostic utility of 18F-FDG PET/CT in fever of unknown origin among patients with end-stage renal disease treated with renal replacement therapy.

OBJECTIVE: To evaluate the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in identifying the cause of fever of unknown origin (FUO) in patients on renal replacement therapy (RRT) for end-stage renal disease (ESRD). SUBJECTS AND METHODS: We retrospectively reviewed the 18F-FDG PET/CT scans of 46 patients with a mean age of 39.28±12.50 years on RRT for ESRD. All patients with abnormal scans had histopathologic examination and microbial cultures of tissue samples from areas with increased standardized uptake value maximum (SUVmax) suggesting the cause of FUO in the 18F-FDG PET/CT scan. Fluorine-18-FDG PET/CT was considered helpful if it led to the diagnosis of the cause of FUO after histopathologic and microbiologic examinations. RESULTS: Fluorine-18-FDG PET/CT was helpful in identifying the cause of FUO in 22/46 patients (47.83%). Infection was the cause of fever in all these 22 patients. C-reactive protein (CRP) (P=0.003) and procalcitonin levels (P=0.021) were higher in patients with helpful 18F-FDG PET/CT. No significant difference was found in blood sugar levels and leucocytes counts between patients with helpful 18F-FDG PET/CT outcome and those without. By multiple regression analysis, the odds of a helpful 18F-FDG PET/CT increased with every unit increase in CRP level (OR: 1.009; 95% CI: 1.003-1.016; P=0.005). CONCLUSION: About half of the 18F-FDG-PET/CT scans (22/46) identified the cause of FUO in patients on RRT for ESRD. The clinical utility of 18F-FDG PET/CT in this group of patients is comparable to its average performance in the unselected patients' population evaluated for FUO. A higher CRP level was predictive of a positive 18F-FDG PET/CT outcome.

Radionuclide imaging of inflammation in atherosclerotic vascular disease among people living with HIV infection: current practice and future perspective.

People living with human immunodeficiency virus (HIV) infection have twice the risk of atherosclerotic vascular disease compared with non-infected individuals. Inflammation plays a critical role in the development and progression of atherosclerotic vascular disease. Therapies targeting inflammation irrespective of serum lipid levels have been shown to be effective in preventing the occurrence of CVD. Radionuclide imaging is a viable method for evaluating arterial inflammation. This evaluation is useful in quantifying CVD risk and for assessing the effectiveness of anti-inflammatory treatment. The most tested radionuclide method for quantifying arterial inflammation among people living with HIV infection has been with F-18 FDG PET/CT. The level of arterial uptake of F-18 FDG correlates with vascular inflammation and with the risk of development and progression of atherosclerotic disease. Several limitations exist to the use of F-18 FDG for PET quantification of arterial inflammation. Many targets expressed on macrophage, a significant player in arterial inflammation, have the potential for use in evaluating arterial inflammation among people living with HIV infection. The review describes the clinical utility of F-18 FDG PET/CT in assessing arterial inflammation as a risk for atherosclerotic disease among people living with HIV infection. It also outlines potential newer probes that may quantify arterial inflammation in the HIV-infected population by targeting different proteins expressed on macrophages.

Arterial inflammation in young patients with human immunodeficiency virus infection: A cross-sectional study using F-18 FDG PET/CT.

BACKGROUND: HIV infection is associated with the risk of development of atherosclerosis at a younger age. We compared arterial inflammation in HIV-infected and HIV-uninfected patients with otherwise low-risk factors for cardiovascular disease (CVD) using FDG PET/CT. METHODS: 242 patients aged 18-40 years with low-risk factors for CVD consisting of 121 HIV-infected patients and 121 HIV-uninfected age- and gender-matched controls were studied, mean age = 34.95 ± 5.46 years. We calculated and compared the target-to-background ratio of FDG uptake in ascending aorta of HIV-infected and non-infected patients. RESULTS: Median CD4 count and viral load were 375.5 cells/mm3 (range 2-1094) and 6391.00 copies/mL (range 24-1,348,622), respectively. There was slightly higher but significant overlap in the TBR between HIV-infected group compared with control (1.22, 0.87-2.02 vs. 1.12, 0.38-1.40, P < 0.001). TBR was neither affected by CD4 count levels nor the presence or absence of detectable viremia. We also found no significant difference in TBR between male and female patients with HIV infection. We found a weak positive correlation between TBR and CD4 count, TBR and duration of HIV infection, and a very weak negative correlation between TBR and viral load. There was no significant difference in TBR between patients on HAART and those not yet commenced on therapy. CONCLUSION: Marginally higher TBR with a significant overlap exist in HIV-infected patients compared with control. Arterial F-18 FDG uptake is not affected by the CD 4 count, viral load, gender, or duration of HIV infection.

Role of FDG PET/CT in monitoring treatment response in patients with invasive fungal infections.

INTRODUCTION: Invasive fungal infections (IFIs) occur mostly in immunosuppressed patients and can be life-threatening. Inadequate treatment is associated with high morbidity and mortality. We examined the role of 2-fluorodeoxyglucose positron emission tomography integrated with CT (FDG-PET/CT) in monitoring IFIs and therapy decision-making, and evaluated the role of baseline metabolic parameters in predicting the metabolic response. METHODS: All patients between October 2009 and March 2018, diagnosed with IFIs, treated with antifungal drugs, and who underwent FDG-PET/CT at baseline and at one or more timepoints during treatment were retrospectively included. The electronic patient files were reviewed for pathology, microbiology, and laboratory findings. All FDG-PET/CT scans were performed according to standardized European Association of Nuclear Medicine/EANM Research Limited (EANM/EARL) protocols. For each scan, the global total lesion glycolysis (TLG) and metabolic volume (MV), highest maximum standardized uptake value (SUVmax), and peak standardized uptake value (SUVpeak) were determined. The role of FDG-PET/CT on monitoring antifungal therapy was assessed by looking at the clinical decision made as result of the scan. Furthermore, the added value of the baseline metabolic parameters in predicting metabolic response to the antifungal treatment was evaluated. RESULTS: Twenty-eight patients with in total 98 FDG-PET/CT scans were included with a mean age of 43 ± 22 years. FDG-PET/CT altered management in 14 out of the 28 patients (50%). At the final FDG-PET/CT scan, 19 (68%) had a complete metabolic response (CMR), seven a partial response and two patients were defined as having progressive disease. Using receiver operative analysis, the cut-off value, sensitivity, specificity, and significance for the baseline TLG and MV to discriminate patients with CMR were 160, 94%, 100%, p < 0.001 and 60, 84%, 75%, p = 0.001 respectively. CONCLUSION: FDG-PET/CT is useful in the monitoring of IFIs resulting in management therapy change in half of the patients. Baseline TLG and MV were found to be able to predict the metabolic response to antifungal treatment.

18F-FDG-PET metabolic metrics and International Prognostic Score for risk assessment in HIV-infected patients with Hodgkin lymphoma.

OBJECTIVES: Baseline metabolic metrics on fluorine-18-fluorodeoxyglucose PET (F-FDG PET) have prognostic value in Hodgkin lymphoma. International Prognostic Score (IPS) is used in the risk stratification of Hodgkin lymphoma. We compared the metabolic indices in HIV-infected and the IPS in HIV-infected and uninfected patients with Hodgkin lymphoma. PATIENTS AND METHODS: We retrospectively reviewed the data of HIV-infected and HIV-uninfected patients with classic Hodgkin lymphoma who had F-FDG PET for staging and compared the maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume, and total lesion glycolysis between the two groups. We also compared the IPS and other prognostic indicators and correlated them with the metabolic indices in the two groups. RESULTS: We studied 160 patients, which included 57 patients who were infected with HIV. The mean age was 33.84±11.88 years, with 38% (n=61) being female. The median cluster of differentiation 4 count and HIV viral load were 259 cells/mm and 4837.50 copies/ml, respectively. No significant difference in maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume, and total lesion glycolysis between the two groups was found. Among the seven parameters of the IPS, only male sex (HIV-uninfected group higher, P=0.005) and serum albumin less than 4 g/dl were significantly different. The other parameters were not significantly different between the two groups. Other prognostic indicators including bulky disease, extranodal involvement, and the number of nodal groups involved were not significantly different between the two groups. CONCLUSION: There was no significant difference in F-FDG metabolic parameters, IPS, and other risk indicators between HIV-infected and HIV-uninfected patients with Hodgkin lymphoma.

Prognostic Value of Pre-treatment F-18 FDG PET Metabolic Metrics in Patients with Locally Advanced Carcinoma of the Anus with and without HIV Infection.

AIM: To investigate the prognostic value of F-18 FDG PET metabolic parameters in patients with anal carcinoma with and without human immunodeficiency virus infection (HIV). METHODS: Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained on F-18 FDG PET/CT images of treatment-naïve patients with locally advanced anal squamous cell carcinoma (ASSC). We compared patients' characteristics and F-18 FDG PET metabolic metrics between the HIV-infected patients and the HIV-uninfected patients. We did a simple Cox regression analysis followed by a multiple Cox regression analysis to determine factors predictive of death. RESULTS: We studied 33 patients including 21 HIV-infected individuals, mean age = 46.06 ± 12.59, female = 16, males = 17. Median CD4 count among HIV-infected patients was 400.50 cells/mm3 (IQR: 304.0 - 642.25). HIV-infected patients were younger than the HIV-uninfected patients at the time of diagnosis; 38.71 ± 7.98 vs. 58.92 ± 7.88 respectively, p < 0.001. No significant difference in the TNM stage and F-18 FDG metabolic parameters between the two groups. In a simple Cox regression analysis, MTV and TLG were significant predictors of death. Following a multiple Cox regression analysis, MTV and SUVmean were significant predictors of death. The median overall survival was 44.63 (95 % CI: 34.12 - 55.14) among HIV-infected patients versus 54.65 (95 % CI: 45.73 - 63.57) among HIV-uninfected patients, p = 0.415. CONCLUSION: HIV-infected patients are diagnosed with ASSC at a younger age compared with HIV-uninfected patients. F-18 FDG PET metabolic metrics especially MTV predicts overall survival in patients with ASCC. There is no difference in the overall survival of HIV-infected and HIV-uninfected patients treated similarly for ASSC. ZIEL:: Die Untersuchung der prognostischen Bedeutung der F-18 FDG PET metabolischen Aktivität bei HIV-negativen und positiven Analkarzinom-Patienten. METHODEN: Bestimmt wurden maximale standardisierten Uptake-Werte (SUVmax), mittlere standardisierte Uptake-Werte (SUVmean), das metabolische Tumorvolumen (MTV) sowie die gesamte Tumorlyse-Glukose (TLG) mittels F-18 FDG PET/CT bei behandlungsnaiven Patienten mit lokal fortgeschrittenem Anal-Plattenepithelkarzinom (ASSC). Die Patientencharakteristika und F-18 FDG PET metabolischen Ergebnisse der HIV-positiven und HIV-negativen Patienten wurden verglichen. Eine einfache Cox-Regressionsanalyse gefolgt von einer multiplen Cox-Regressionsanalyse diente der Bestimmung von Faktoren für Tod. ERGEBNISSE: Wir untersuchten 33 Patienten, davon 21 HIV-Infizierte, mittleres Alter = 46,06 ± 12,59, Frauen = 16, Männer = 17. Die mediane CD4-Zahl unter den HIV-Patienten war 400,50 Zellen/mm3 (IRQ: 304,0 - 642,25). Die HIV-infizierten Patienten waren jünger als die HIV-negativen Patienten zum Zeitpunkt der Diagnose; 38,71 ± 7,98 vs. 58,92 ± 7,88, p < 0,001. Es gab keinen signifikanten Unterschied in der TNM-Klassifikation und in den F-18 FDG metabolischen Werten zwischen den beiden Gruppen. In einer einfachen Cox-Regressionsanalyse waren MTV und TLG signifikante Prädiktoren für Tod. Das mediane Gersamtüberleben lag bei 44,63 (95 % CI: 34,12 - 55,14) unter den HIV-infizierten Patienten vs. 54,65 (95 % CI: 45,73 - 63,57) unter den HIV-negativen Patienten, p = 0,415. SCHLUSSFOLGERUNGEN: HIV-infizierte Patienten werden in jüngeren Jahren mit ASSC diagnostiziert im Vergleich zu HIV-negativen Patienten. F-18 FDG PET metabolische Aktivität, insbesondere MTV, kann das Gesamtüberleben von Patienten mit ASCC vorhersagen. Es gibt keinen Unterschied im Gesamtüberleben von HIV-infizierten und HIV-negativen Patienten bei gleicher Therapie des ASSC.

New Imaging Tracers for the Infected Diabetic Foot (Nuclear and Optical Imaging).

Diabetic Foot Infections (DFIs) are associated with increased morbidity, an economic burden on patients, their families and healthcare systems and increased mortality. Early diagnosis with prompt, appropriate and adequate treatment of the infected diabetic foot is crucial. The determination of DFIs, however, may be quite perplexing and invasive. Imaging is useful in the evaluation of certain cases of DFIs, especially in suspected instances with no overt clinical features, or in the diagnosis of osteomyelitis. Nuclear medicine imaging is currently used in the evaluation of DFIs; however, like all the imaging techniques now available, it has its limitations. Several radiopharmaceuticals presently available play useful roles in the management of DFIs, while new ones are being evaluated. Optical imaging techniques have recently demonstrated promising results in the evaluation of many infections including DFIs. Using the same molecule, a tracer can be labeled with a radioisotope or an optical imaging dye. This enables infections to be evaluated both pre- and intra-operatively when surgery is required in their management. In some cases, tracers have been simultaneously labeled with both a radioisotope and an optical imaging dye to produce a hybrid tracer. These new tracers potentially provide powerful and new opportunities in the management of DFIs. In this review, we briefly examine tracers that have been used in the evaluation of the infected diabetic foot. We then explore the potential of new imaging tracers currently under development for infection that may be useful in the management of DFIs.