Dual time-point FDG PET/CT for differentiating benign from malignant solitary pulmonary nodules in a TB endemic area

Objective. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is an accurate non-invasive imaging test for differentiating benign from malignant solitary pulmonary nodules (SPNs). We aimed to assess its diagnostic accuracy for differentiating benign from malignant SPNs in a tuberculosis (TB)-endemic area. Methods. Thirty patients, 22 men and 8 women, mean age 60 years, underwent dual time point FDG-PET/computed tomography (CT) imaging, followed by histological examination of the SPN. Maximum standard uptake values (SUVmax) with the greatest uptake in the lesion were calculated for two time points (SUV1 and SUV2), and the percentage change over time per lesion was calculated (%DSUV). Routine histological findings served as the gold standard. Results. Histological examination showed that 14 lesions were malignant and 16 benign, 12 of which were TB. SUVmax for benign and malignant lesions were 11.02 (standard deviation (SD) 6.6) v. 10.86 (SD 8.9); however, when tuberculomas were excluded from the analysis, a significant difference in mean SUV1max values between benign and malignant lesions was observed (p=0.0059). Using an SUVmax cut-off value of 2.5, a sensitivity of 85.7% and a specificity of 25% was obtained. Omitting the TB patients from analysis resulted in a sensitivity of 85.7% and a specificity of 100%. Mean %DSUV of benign lesions did not differ significantly from mean %DSUV of malignant lesions (17.1% (SD 16.3%) v. 19.4% (SD 23.7%)). Using a cut-off of %DSUV >10% as indicative of malignancy, a sensitivity of 85.7% and a specificity of 50% was obtained. Omitting the TB patients from the analysis yielded a sensitivity of 85.7% and a specificity of 75%. Conclusion. Our findings suggest that FDG-PET cannot distinguish malignancy from tuberculoma and therefore cannot reliably be used to reduce futile biopsy/thoracotomy

Blood-brain barrier transport kinetics of NOTA-modified proteins : the somatropin case

BACKGROUND: Chemical modifications such as PEG, polyamine and radiolabeling on proteins can alter their pharmacokinetic behaviour and their blood-brain barrier (BBB) transport characteristics. NOTA, i.e. 1,4,7-triazacyclononane-1,4,7-triacetic acid, is a bifunctional chelating agent that has attracted the interest of the scientific community for its high complexation constant with metals like gallium. Until now, the comparative BBB transport characteristics of NOTA-modified proteins versus unmodified proteins are not yet described. METHODS: Somatropin (i.e. recombinant human growth hormone), NOTA-conjugated somatropin and gallium-labelled NOTA-conjugated somatropin were investigated for their brain penetration characteristics (multiple time regression and capillary depletion) in an in vivo mice model to determine the blood-brain transfer properties. RESULTS: The three compounds showed comparable initial brain influx, with Kin = 0.38 ± 0.14 µL/(g×min), 0.36 ± 0.16 µL/(g×min) and 0.28 ± 0.18 µL/(g×min), respectively. Capillary depletion indicated that more than 80% of the influxed compounds reached the brain parenchyma. All three compounds were in vivo stable in serum and brain during the time frame of the experiments. CONCLUSIONS: Our results show that modification of NOTA as well as gallium chelation onto proteins, in casu somatropin, does not lead to a significantly changed pharmacokinetic profile at the blood-brain barrier

PSMA-targeting positron emission agents for imaging solid tumors other than non-prostate carcinoma : a systematic review

Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a wide variety of solid tumors other than prostate carcinoma. Accordingly, positron-emitting radiolabeled small molecules targeting PSMA, initially developed for positron emission tomography in prostate carcinomas, are currently being explored for their staging and restaging potential as an alternative imaging modality in other solid tumor types where 18-F-fluorodeoxyglucose (FDG)-PET imaging has low diagnostic accuracy. In this paper, the currently available literature in this field is reviewed. Preliminary, mainly retrospective studies are encouraging, with evidence of improved diagnostic sensitivity and specificity in clear cell renal carcinoma, glioma, and hepatocellular carcinoma, leading to a change in patient management in several patients. However, the results published thus far warrant confirmation by larger prospective studies additionally assessing the longitudinal impact on patient outcomes

Occurence and characterisation of biofilms in drinking water systems of broiler houses

Background: Water quality in the drinking water system (DWS) plays an important role in the general health and performance of broiler chickens. Conditions in the DWS of broilers are ideal for microbial biofilm formation. Since pathogens might reside within these biofilms, they serve as potential source of waterborne transmission of pathogens to livestock and humans. Knowledge about the presence, importance and composition of biofilms in the DWS of broilers is largely missing. In this study, we therefore aim to monitor the occurrence, and chemically and microbiologically characterise biofilms in the DWS of five broiler farms. Results: The bacterial load after disinfection in DWSs was assessed by sampling with a flocked swab followed by enumerations of total aerobic flora (TAC) and Pseudomonas spp. The dominant flora was identified and their biofilm-forming capacity was evaluated. Also, proteins, carbohydrates and uronic acids were quantified to analyse the presence of extracellular polymeric substances of biofilms. Despite disinfection of the water and the DWS, average TAC was 6.031.53 log CFU/20cm(2). Enumerations for Pseudomonas spp. were on average 0.88 log CFU/20cm(2) lower. The most identified dominant species from TAC were Stenotrophomonas maltophilia, Pseudomonas geniculata and Pseudomonas aeruginosa. However at species level, most of the identified microorganisms were farm specific. Almost all the isolates belonging to the three most abundant species were strong biofilm producers. Overall, 92% of all tested microorganisms were able to form biofilm under lab conditions. Furthermore, 63% of the DWS surfaces appeared to be contaminated with microorganisms combined with at least one of the analysed chemical components, which is indicative for the presence of biofilm. Conclusions: Stenotrophomonas maltophilia, Pseudomonas geniculata and Pseudomonas aeruginosa are considered as opportunistic pathogens and could consequently be a potential risk for animal health. Additionally, the biofilm-forming capacity of these organisms could promote attachment of other pathogens such as Campylobacter spp. and Salmonella spp

811-1 Evolution of Left Ventricular Function, Myocardial Perfusion and Metabolism in Infarct Patients After Coronary Thrombolysis

Follow-up of regional myocardial blood flow, metabolism and function was studied in a population of thrombolysed patients. Fifty one patients with an acute myocardial infarction were prospectively enrolled. All patients received thrombolytic therapy within 6 hours after the onset of symptoms. Coronary angiography, 2D-echocardiography and 13NH3/18FDG PET were performed 5 days after the acute event. Three months after the infarction, 2D-echocardiography and 13NH3/18FDG PET studies were repeated.Thirty six patients (62% with TIMI III, 7% with TIMI II) revealed a concordant decrease of flow and metabolism in the infarct area (PET match). Fifteen patients (33% with TIMI III, 13% with TIMI II) revealed a decrease of flow with preservation of metabolism (PET mismatch). Twelve patients received further treatment (PTCA or CAGB) after the first PET scan. Myocardial blood flow improved significantly in both match (71±17ml/min/l00g at 3 months versus 60±17ml/min/100 g at 5 days, p<0.01) and mismatch groups (71±26ml/min/l00 g at 3 months versus 63 ±18ml/min/100 g at 5 days, p<0.05). Blood flow in remote areas did not change significantly (84±18mllmin/l 00 g at 3 months versus 82±19ml/min/l 00 gat 5 days, p=NS). In 4 patients with a match pattern at 5 days, a mismatch pattern had developed 3 months after the acute event.Functional follow-up was performed in 30 patients, 23 with a match pattern and 7 with a mismatch pattern. A variable outcome was observed: In 3 out of 7 mismatch areas contractility did not improve. On the contrary, 9 out of 23 match areas revealed functional improvement.It can be concluded that in this population of early thrombolysed patients, few mismatches were observed (29%). Flow values improved significantly in both match and mismatch groups 3 months after the acute event. In some patients, a mismatch pattern was found after 3 months, suggesting the need for further treatment. Functional outcome was variable, probably due to a variety of pathophysiologic processes such as stunning shortly after reperfusion with functional improvement after 3 months, reocclusion or progression of coronary artery disease resulting in reinfarction or hibernation

Impact of FDG PET on the management of TBC treatment

The AIM: of this study is to assess the potential impact of double-phase FDG PET versus routine staging in HIV-negative patients suffering from tuberculosis. PATIENTS, METHODS: 16 consecutive patients suffering from tuberculosis underwent contrast-enhanced CT and double-phase FDG PET imaging (45 min, 120 min). Early (E) and delayed (D) SUVmax values were determined for all identified lesions and % change in SUV calculated (ΔSUV). RESULTS: Seven patients presented with lung lesions on PET as well as CT (mean SUVmaxE 8.2, mean SUVmaxD 11.1, (p = 0.002), ΔSUV 35%. In two patients, lesions were judged as non-active on CT. In nine patients, 18 sites of LN involvement were identified on both early and delayed FDG PET images (mean SUVmaxE 6.3, mean SUVmaxD 7.9, (p = 0.0001), ΔSUV: 25%). 9 out of 18 sites of LN involvement, occurring in five patients, were missed on CT. In four of these five patients, sites of LN involvement were the only sites of extra-pulmonary involvement identified. In 6 out of 16 patients, pleural involvement was identified, respectively in 5 on FDG PET and in 6 on CT imaging (mean SUVmaxE 1.3, mean SUVmaxD 1.7, (p = 0.06), ΔSUV 21%). In 4 patients, osseous involvement was identified by both FDG PET and CT (mean SUVmaxE 7.2, mean SUVmaxD 10.7, (p = 0,06), ΔSUV 45%). Finally, in 3 patients, joint involvement was identified on both FDG PET as well as on CT imaging (mean SUVmaxE 4.7, mean SUVmaxD 5.2, ΔSUV 23%). FDG PET did not identify CTadditional sites of involvement that would have resulted in a prolonged treatment. CONCLUSION: In HIV-negative patients suffering from tuberculosis, FDG PET images suggested a more extensive involvement by Mycobacterium tuberculosis when compared to contrast enhanced CT.Ziel dieser Studie ist die Beurteilung eines möglichen Einflusses der 2-Phasen-FDG-PET im Vergleich zum Routine-Staging bei HIV-negativen Patienten mit Tuberkulose. PATIENTEN, METHODEN: Bei 16 aufeinanderfolgenden Patienten mit Tuberkulose wurden ein kontrastverstärktes CT sowie eine 2-Phasen-FDG-PET (45 min, 120 min) durchgeführt. Frühe (E) und späte (D) SUVmax-Werte wurden für alle dargestellten Läsionen bestimmt; die prozentuale Veränderung der SUV (ΔSUV) wurde berechnet. ERGEBNISSE: Bei sieben Patienten zeigten sich pulmonale Herde sowohl in der PET als auch im CT (mittlere SUVmaxE 8,2, mittlere SUVmaxD 11,1, (p = 0,002), ΔSUV 35%). Bei zwei Patienten wurden die Läsionen im CT als nicht aktiv beurteilt. Bei neun Patienten wurde sowohl in den frühen als auch in den späten FDG-PET-Aufnahmen ein Lymphknotenbefall an 18 Stellen identifiziert (mittlere SUVmaxE 6,3, mittlere SUVmaxD 7,9, (p = 0,0001), ΔSUV 25%). Bei fünf Patienten fehlten im CT 9 der 18 befallenen Lymphknoten. Bei vier dieser fünf Patienten stellte der Lymphknotenbefall die einzige extrapulmonale Beteiligung dar. Bei 6/16 Patienten wurde eine pleurale Beteiligung festgestellt, bei 5 in der FDG-PET bzw. bei 6 im CT (mittlere SUVmaxE 1,3, mittlere SUVmaxD 1,7, (p = 0,06), ΔSUV 21 %). Bei 4 Patienten wurde eine Knochenbeteiligung sowohl in der FDG-PET als auch im CT diagnostiziert (mittlere SUVmaxE 7,2, mittlere SUVmaxD 10,7, (p = 0,06), ΔSUV 45%). Schließlich wurde bei 3 Patienten ein Befall der Gelenke sowohl in der FDG-PET als auch im CT festgestellt (mittlere SUVmaxE 4,7, mittlere SUVmaxD 5,2, ΔSUV 23%). In der FDG-PET konnte kein über das CT hinausgehender Befall festgestellt werden, der zu längerer Behandlungsdauer geführt hätte. SCHLUSSFOLGERUNG: Bei HIV-negativen Patienten mit Tuberkulose können die FDG-PET-Aufnahmen einen ausgedehnteren Befall mit Mycobacterium tuberculosis vermuten lassen als das kontrastverstärkte CT

Accuracy of bone SPECT/CT for identifying hardware loosening in patients who underwent lumbar fusion with pedicle screws

BACKGROUND : The aim of this retrospective study was to evaluate the accuracy of bone SPECT (single photon emission computed tomography)/CT (computed tomography) in diagnosing loosening of fixation material in patients with recurrent or persistent back pain that underwent lumbar arthrodesis with pedicle screws using surgery and clinical follow-up as gold standard Methods A total of 48 patients (median age 49 years, range 21–81 years; 17 men) who had undergone lumbar spinal arthrodesis were included in this retrospective analysis. SPECT/ CT results were compared to the gold standard of surgical evaluation or clinical follow-up. Positive SPECT/CT results were considered true positives if findings were confirmed by surgery or if clinical and other examinations were completely consistent with the positive SPECT/CT finding. They were considered false positives if surgical evaluation did not find any loose pedicle screws or if symptoms subsided with non-surgical therapy. Negative SPECT/CT scans were considered true negatives if symptoms either improved without surgical intervention or remained stable over a minimum follow-up period of 6 months. Negative SPECT/CTscanswere determined to be false negatives if surgery was still required and loosening of material was found. RESULTS : The median length of time from primary surgery to bone SPECT/CT referral was 29.5 months (range 12– 192 months). Median follow-up was 18 months (range 6– 57) for subjects who did not undergo surgery. Thirteen of the 48 patients were found to be positive for loosening on bone SPECT/CT. Surgical evaluation (8 patients) and clinical follow-up (5 patients) showed that bone SPECT/CT correctly predicted loosening in 9 of 13 patients, while it falsely diagnosed loosening in 4 patients.Of 35 negative bone SPECT/CT scans, 12 were surgically confirmed. In 18 patients, bone SPECT/CT revealed lesions that could provide an alternative explanation for the symptoms of pain (active facet degeneration in 14 patients, and disc and sacroiliac osteodegeneration in 7 patients and 1 patient, respectively). Overall sensitivity and specificity for the detection of loosening were 100 % and 89.7 %, respectively. The positive and negative predictive values were 69 % and 100 %, respectively. CONCLUSIONS : This retrospective analysis suggests that bone SPECT/CT bone is a highly sensitive and specific tool for the exclusion of screw loosening in patients who present with recurrent low back pain after having undergone lumbar arthrodesis. In addition, it can identify other potential causes of recurrent low back pain in this patient population.http://link.springer.com/journal/2592017-02-20hb201

Evaluating the possible role of 68Ga-citrate PET/CT in the characterization of indeterminate lung lesions

We sought to determine whether PET/CT imaging with 68Ga-citrate could be of value in distinguishing benign from malignant lung pathology in a setting with a high prevalence of granulomatous diseases. METHODS : Thirty-six consecutive patients with indeterminate lung lesions prospectively underwent dual time point (60 and 120 min) 68Ga-citrate PET/CT study prior to lung biopsy. Qualitative and semi-quantitative measures of tracer uptake in the lung lesions (SUVmax) were compared to the histopathology in order to establish an imaging pattern to distinguish benign from malignant lesions. RESULTS : Fourteen patients (38.9 %) were diagnosed with a malignant lesion, 12 (33.3 %) with tuberculosis (TB), and 10 participants (27.8 %) with other benign lung lesions. At 60-min post-injection, patients who were diagnosed with a malignant lesion (n = 14) demonstrated a mean SUVmax of 3.36 ± 1.14, with a median value of 3.04 (min = 1.56, max = 4.65).Those with TB (n = 12) demonstrated a SUVmax of 3.99 ± 2.28, and a median value of 3.71 (pct25 = 2.19, pct75 = 4.95). In patients with other benign lesions (n = 10), the following values were observed: a SUVmax of 2.70 ± 1.31, a median value of 2.50 (pct25 = 1.76, pct75 = 3.59). The mean values of these three types of pathology were not statistically significant (p = 0.1919), and therefore the SUVmax could not be used to accurately distinguish between these lesions using both early and delayed imaging. CONCLUSION : This study, as the first 68Ga-citrate PET/CT in humans for the in vivo imaging of lung pathology, demonstrated its potential for the detection of both malignancy and TB. However, 68Ga-citrate seemed incapable of providing a clear distinction between malignant and benign lung lesions in a setting with a high prevalence of granulomatous diseases such as TB.http://link.springer.com/journal/12149hb201