Search

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

Radiomics or textural feature extraction obtained from positron emission tomography (PET) images through complex mathematical models of the spatial relationship between multiple image voxels is currently emerging as a new tool for assessing intra-tumoral heterogeneity in medical imaging. In this paper, available literature on texture analysis using FDG PET imaging in patients suffering from tumors of the gastro-intestinal tract is reviewed. While texture analysis of FDG PET images appears clinically promising, due to the lack of technical specifications, a large variability in the implemented methodology used for texture analysis and lack of statistical robustness, at present, no firm conclusions can be drawn regarding the predictive or prognostic value of FDG PET texture analysis derived indices in patients suffering from gastro-enterologic tumors. In order to move forward in this field, a harmonized image acquisition and processing protocol as well as a harmonized protocol for texture analysis of tumor volumes, allowing multi-center studies excluding statistical biases should be considered. Furthermore, the complementary and additional value of CT-imaging, as part of the PET/CT imaging technique, warrants exploration. ispartof: BIOMEDICINES vol:8 issue:9 ispartof: location:Switzerland status: published

BACKGROUND: Chemical modifications such as PEG, polyamine and radiolabeling on proteins can alter their pharmacokinetic behavior 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 [CD]) 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. CD 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. ispartof: QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING vol:64 issue:1 pages:105-114 ispartof: location:Italy status: published

BACKGROUND: The aim of this study was to compare liver and oncologic lesion standardized uptake values (SUV) obtained through two different reconstruction protocols, GE's newest clinical lesion detection protocol (Q.Clear) and the EANM Research Ltd (EARL) harmonization protocol, and to assess the clinical relevance of potential differences and possible implications for daily clinical practice using the PERCIST lesional inclusion criteria. NEMA phantom recovery coefficients (RC) and SUV normalized for lean body mass (LBM), referred to as SUV normalized for LBM (SUL), of liver and lesion volumes of interest were compared between the two reconstruction protocols. Head-to-toe PET/CT examinations and raw data from 64 patients were retrospectively retrieved. PET image reconstruction was carried out twice: once optimized for quantification, complying with EARL accreditation requirements, and once optimized for lesion detection, according to GE's Q.Clear reconstruction settings. RESULTS: The two reconstruction protocols showed different NEMA phantom RC values for different sphere sizes. Q.Clear values were always highest and exceeded the EARL accreditation maximum for smaller spheres. Comparison of liver SULmean showed a statistically significant but clinically irrelevant difference between both protocols. Comparison of lesion SULpeak and SULmax showed a statistically significant, and clinically relevant, difference of 1.64 and 4.57, respectively. CONCLUSIONS: For treatment response assessment using PERCIST criteria, the harmonization reconstruction protocol should be used as the lesion detection reconstruction protocol using resolution recovery systematically overestimates true SUL values. ispartof: EJNMMI PHYSICS vol:5 issue:1 ispartof: location:Germany status: published

Background: Emerging data from published studies are demonstrating the superiority of Ga-68 PSMA PET/CT imaging in prostate cancer. However, the low yield of the Ge68/Ga-68 from which Gallium-68 is obtained and fewer installed PET/CT systems compared to the SPECT imaging systems may limit its availability. We, therefore, evaluated in a head-to-head comparison, the diagnostic sensitivity of Ga-68 PSMA PET/CT and Tc-99m PSMA SPECT/CT in patients with prostate cancer.Methods: A total of 14 patients with histologically confirmed prostate cancer were prospectively recruited to undergo Ga-68 PSMA PET/CT and Tc-99m HYNIC PSMA SPECT/CT. The mean age of patients was 67.21 +/- 8.15 years and the median PSA level was 45.18 ng/mL (range = 1.51-687 ng/mL). SUVmax of all lesions and the size of lymph nodes with PSMA avidity on Ga-68 PSMA PET/CT were determined. Proportions of these lesions detected on Tc-99m HYNIC PSMA SPECT/CT read independent of PET/CT findings were determined.Results: A total of 46 lesions were seen on Ga-68 PSMA PET/CT localized to the prostate (n = 10), lymphnodes (n = 24), and bones (n = 12). Of these, Tc-99m HYNIC PSMA SPECT/CT detected 36 lesions: Prostate = 10/10 (100%), lymph nodes = 15/24 (62.5%), and bones = 11/12 (91.7%) with an overall sensitivity of 78.3%. Lesions detected on Tc-99m HYNIC PSMA SPECT/CT were bigger in size (P Conclusion: Tc-99m HYNIC PSMA may be a useful in imaging of prostate cancer although with a lower sensitivity for lesion detection compared to Ga-68 PSMA PET/CT. Its use is recommended when Ga-68 PSMA is not readily available, in planning radio-guided surgery or the patient is being considered for radio-ligand therapy with Lu-177 PSMA. It performs poorly in detecting small-sized lesions hence its use is not recommended in patients with small volume disease.

BACKGROUND: The Hopkins criteria were introduced for nodal response evaluation after therapy in head and neck cancer, but its superiority over quantification is not yet confirmed.METHODS: SUVbody weight thresholds and lesion-to-background ratios were explored in a prospective multicenter study of standardized FDG-PET/CT 12 weeks after CRT in newly diagnosed locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients (ECLYPS). Reference standard was histology, negative FDG-PET/CT at 12 months after treatment or ≥ 2 years of negative follow-up. Area under the receiver operator characteristics curves (AUROC) were estimated and obtained thresholds were validated in an independent cohort of HNSCC patients (n = 127).RESULTS: In ECLYPS, 124 patients were available for quantification. With a median follow-up of 20.4 months, 23 (18.5%) nodal neck recurrences were observed. A SUV70 threshold of 2.2 (AUROC = 0.89; sensitivity = 79.7%; specificity = 80.8%) was identified as optimal metric to identify nodal recurrence within 1 year after therapy. For lesion-to-background ratios, an SUV50/SUVliver threshold of 0.96 (AUROC = 0.89; sensitivity = 79.7%; specificity = 82.8%) had the best performance. Compared with Hopkins criteria (AUROC = 0.81), SUV70 and SUV50/SUVliver provided a borderline significant (p = 0.040 and p = 0.094, respectively) improvement. Validation of thresholds yielded similar AUROC values (SUV70 = 0.93, SUV50/SUVliver = 0.95), and were comparable to the Hopkins score (AUROC = 0.91; not statistically significant).CONCLUSION: FDG quantification detects nodal relapse in LAHNSCC patients. When using EARL standardized PET acquisitions and reconstruction, absolute SUV metrics (SUV70 threshold 2.2) prove robust, yet ratios (SUV50/SUVliver, threshold 0.96) may be more useful in routine clinical care. In this setting, the diagnostic value of quantification is comparable to the Hopkins criteria.TRIAL REGISTRATION: US National Library for Medicine, NCT01179360. Registered 11 August 2010, https://clinicaltrials.gov/ct2/show/NCT01179360.

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. ispartof: NUKLEARMEDIZIN-NUCLEAR MEDICINE vol:57 issue:5 pages:190-197 ispartof: location:Germany status: published

Aims Cardiomyocyte apoptosis is known to occur in infarct border zones, where cardiomyocyte dedifferentiation, as seen in hibernating myocardium, can also be observed. The aim of the study is to determine whether dedifferentiated cardiomyocytes represent a population of cells stably surviving or undergoing apoptosis. Methods and Results Microinfarctions were induced in sheep (n = 8) by intracoronary injection of polymer macrobeads. The sheep were killed when cardiac function was gradually decreased (ejection fraction 37 +/- 6%, mean +/- SEM), but not earlier than 6 weeks after embolization. Transmural biopsies were taken from embolized and remote areas, based on flow measurements with positron emission tomography. Cells were classified as dedifferentiated when sarcomere content was depleted by >10%, and glycogen content increased. Apoptosis was detected using the Tdt-mediated nick-end labelling (TUNEL) method and activated caspase-3 immunolabelling. Dedifferentiated cardiomyocytes were identified by morphology and by immunohistochemical evaluation of dedifferentiation related expression patterns of desmin, titin. cardiotin and a-smooth muscle actin. Cardiomyocyte apoptosis was detected in both the infarction border zones and remote areas. Dedifferentiated cardiomyocytes accounted for up to 30%. of the cells in embolized areas and were almost exclusively non-apoptotic. Conclusion In embolization induced microinfarcted tissue, dedifferentiated cardiomyocytes are preferentially spared to undergo apoptosis. It is hypothesized that dedifferentiated cardiomyocytes and apoptotic cardiomyocytes represent two different cell populations. The dedifferentiated cells can be considered as stable surviving cells.

Background: \ud Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent.\ud \ud Methods:\ud In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected.\ud \ud Results:\ud Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs −5%) and n-6 GLA (42% vs −20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs −1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters.\ud \ud Conclusions:\ud Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters.\ud Trial registration: ClinicalTrials.gov Identifier NCT01596933.

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.

Background Inflammatory responses induced by reperfusion of previously ischemic myocardial tissue may lead to further damage of the microvascular structures. A group of cell adhesion molecules, named selectins, initiate those inflammatory changes at the endothelial wall surface. Recombinant P-selectin glycoprotein ligand–immunoglobulin (rPSGL-Ig), a P-selectin antagonist, was shown to have beneficial effects in several animal models of acute myocardial ischemia. We performed a mechanistic study with positron emission tomography to test the potential benefits of rPSGL-Ig in patients with ST-segment elevation acute myocardial infarction. Methods Patients with ST-elevation acute myocardial infarction presenting within the first 6 hours of onset of chest pain were enrolled. All patients received alteplase. Patients were randomly assigned in a 1:1:1 ratio to 3 treatment groups: placebo; 75 mg rPSGL-Ig; 150 mg rPSGL-Ig, given intravenously. Coronary angiography was performed 90 minutes after the start of thrombolytic therapy for TIMI flow grading. Myocardial blood flow (MBF) was measured with 13 NH 3 at rest and after adenosine administration on day 5. Myocardial blood flow at rest was measured again at day 30, followed by measurement of 18 FDG uptake. In addition, a multigated acquisition, gated equilibrium blood pool study was performed at day 30. Continuous 12-lead electrocardiogram recording was performed during the first 24 hours. Results The trial was prematurely stopped by the sponsor for lack of efficacy in an accompanying larger trial after enrolling 88 patients in the current study. Median MBF in the infarct-related territory (expressed as percentage of the normalized blood flow) at day 5 was similar in the 3 treatment groups (9.1% in the placebo group vs 3.8% in the 75-mg dose and 4.3% in the 150-mg rPSGL-Ig treatment group; P = not significant). No significant differences in MBF reserve, myocardial metabolism, ST-segment resolution, left ventricular ejection fraction, or TIMI flow grade were found among the 3 groups. Conclusions In this prematurely stopped mechanistic study, there was no evidence of a benefit of rPSGL-Ig given as an adjunct to thrombolysis on epicardial vessel patency, myocardial tissue reperfusion, or recovery of function.

Background The functional significance of the anterograde and retrograde filling of coronaries on angiography is controversial. Methods and Results Eighteen patients with 27 severe lesions (>85% diameter stenosis) after previous extensive myocardial infarction were selected. The left ventricle was divided into 33 segments for regional comparison of epicardial flow (as assessed by angiography) and tissue perfusion as well as metabolism (as measured by 13NH3− and 18FDG-PET). Viability was defined as normal perfusion (>80% relative of maximum 13NH3 activity) or mismatch defect (> 1.2 metabolismlfiow ratio). A method has been developed to register the ‘lesion predicted region’, determined on the basis of angiography, in the same polar map as derived from the positron emission tomography data. Distal to the lesion, the anterograde epicardial flow was evaluated by Thrombolysis in Myocardial Infarction (TIMI) criteria (TIMI flow 0–3), and retrograde filling was graded on a 0–3 scale (collateral grade 0–3). TIMI flow grade and retrograde collateral grade in every lesion predicted region segment were summed to indicate the total segmental epicardial flow. Out of the 594 segments, 369 were associated with a severe lesion. Among them, significantly higher average perfusion and metabolic activities were found in segments of good epicardial filling (summed epicardial flow ≥ 3) than in the territories of limited epicardial flow (summed score >3): 65.4 ± 17% vs 45.6 ± 10 ( P =0.001%) and 68.6 ± 16% vs 47.4 ± 11% (P=0.0004), respectively. However, when we analysed the predictive value of angiographically detectable good epicardial flow for positron emission tomography viability criteria then the positive predictive value was found to be as low as 0.5, while the negative predictive value was considerably higher (0.82). Conclusion After myocardial infarction, angiographically detectable limited epicardial flow reveals scarred segments while good epicardial contrast filling does not necessarily indicate maintenance of nutritive function.

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 13 NH 3 / 18 FDG PET were performed 5 days after the acute event. Three months after the infarction, 2D-echocardiography and 13 NH 3 / 18 FDG 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 ± 17 ml/min/l00 g at 3 months versus 60 ± 17 ml/min/100 g at 5 days, p l 0.01) and mismatch groups (71 ± 26 ml/min/l00 g at 3 months versus 63 ± 18 ml/min/100 g at 5 days, p l 0.05). Blood flow in remote areas did not change significantly (84 ± 18 mllmin/l 00 g at 3 months versus 82 ± 19 ml/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.