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Purpose: Two types of CT images (modalities) are acquired in PET/CT: for attenuation correction (AC) and diagnosis. The purpose of the study was to compare nodule detection and localization performance between these two modalities., Methods: CT images, using both modalities, of an anthropomorphic chest phantom containing zero or more simulated spherical nodules of 5, 8, 10 and 12 mm diameters and contrasts -800, -630 and 100 HU were acquired. An observer performance study using nine observers interpreting 45 normal (zero nodules) images and 47 abnormal images (1-3 nodules; average 1.26) was conducted using the free-response receiver operating characteristic (FROC) paradigm. Data were analysed using an R software package implemented jackknife alternative FROC (JAFROC) analysis. Both empirical areas under the equally weighted AFROC curve (wAFROC) and under the highest rating inferred ROC (HR-ROC) curve were used as figures of merit (FOM). To control the probability of Type I error test alpha was set at 0.05., Results: Nodule detection as measured by either FOM was significantly better on the diagnostic quality images (2nd modality), irrespective of the method of analysis, [reader averaged inter-modality wAFROC FOM difference = -0.07 (-0.11,-0.04); reader averaged inter-modality HR-ROC FOM difference = -0.05 (-0.09, -0.01)]., Conclusion: Nodule detection was statistically worse on images acquired for AC; suggesting that images acquired for AC should not be used to evaluate pulmonary pathology., (Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

Objective: To quantify neutrophil migration into the lungs of patients with chronic pulmonary obstructive disease (COPD)., Methods: Neutrophil loss via airways was assessed by dedicated whole-body counting 45 min, 24 h and 2, 4, 7 and 10 days after injection of very small activities of (111)In-labelled neutrophils in 12 healthy nonsmokers, 5 healthy smokers, 16 patients with COPD (of whom 7 were ex-smokers) and 10 patients with bronchiectasis. Lung accumulation of (99m)Tc-labelled neutrophils was assessed by sequential SPECT and Patlak analysis in six COPD patients and three healthy nonsmoking subjects., Results: Whole body (111)In counts, expressed as percentages of 24 h counts, decreased in all subjects. Losses at 7 days (mean ± SD) were similar in healthy nonsmoking subjects (5.5 ± 1.5%), smoking subjects (6.5 ± 4.4%) and ex-smoking COPD patients (5.8 ± 1.5%). In contrast, currently smoking COPD patients showed higher losses (8.0 ± 3.0%) than healthy nonsmokers (p = 0.03). Two bronchiectatic patients lost 25% and 26%, indicating active disease; mean loss in the remaining eight was 6.9 ± 2.5%. The rate of accumulation of (99m)Tc-neutrophils in the lungs, determined by sequential SPECT, was increased in COPD patients (0.030-0.073 min(-1)) compared with healthy nonsmokers (0-0.002 min(-1); p = 0.02)., Conclusion: In patients with COPD, sequential SPECT showed increased lung accumulation of (99m)Tc-labelled neutrophils, while whole-body counting demonstrated subsequent higher losses of (111)In-labelled neutrophils in patients who continued to smoke. Sequential SPECT as a means of quantifying neutrophil migration deserves further evaluation.

Background: There is increasing interest in the 'homing' of neutrophils to bone marrow. The aim of this study was to measure the whole-body redistribution of (111) In using a whole-body counter following the administration of ultra-small activities of (111) In-labelled neutrophils., Methods: The detectors of a dedicated whole-body counter were fitted with lead collimators. Whole-body (111) In distribution was recorded at 45 min, 24 h, and 2, 4, 7 and 10 days after administration of (111) In-labelled neutrophils (0·29-0·74 MBq) in eight healthy non-smokers, five healthy smokers, eight patients with inactive bronchiectasis, three with asthma and nine with chronic obstructive pulmonary disease (COPD)., Results: Intravascular 45-min (111) In-labelled neutrophil recovery was not significantly different between groups, ranging from 33 (SD 8%) in healthy smokers to 45 (14%) in healthy non-smokers (P > 0·05). Peaks were identified on the whole body count profile corresponding to the chest, upper abdomen (liver/spleen) and pelvis (bone marrow). (111) In distribution changed between 45 min and 24 h and then remained stable thereafter. Peak chest counts increased ∼ 1·5-fold between 45 min and 24 h, whereas upper abdominal peak counts decreased by ∼ 25% with no significant inter-group differences. The increment in pelvic counts (∼ 2·7-fold) was similar between groups, except COPD patients, in whom it was 2·04 (0·35; P < 0·02 vs. healthy participants)., Conclusions: Assuming neutrophils are distributed only between blood, liver, spleen and bone marrow, the data suggest that marrow pools 25% and destroys 67% of circulating neutrophils, rising in COPD to 40% and 80%, respectively, possibly as a result of the effects on marrow of chronic hypoxaemia., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: The clearance rate of inhaled 99mTc-sestamibi from the lungs of healthy nonsmoking individuals is much slower than would be expected from its physical properties. The clearance rate is even slower in healthy cigarette smokers. As 99mTc-sestamibi is a substrate for P-glycoprotein (P-gp), pulmonary P-gp may be influential in 99mTc-sestamibi clearance and may be upregulated in smokers. 99mTc-tetrofosmin is also a substrate for P-gp, therefore we hypothesized that it would display similar kinetics to 99mTc-sestamibi and support a role for P-gp. We also hypothesized that administration of P-gp modulators would accelerate clearance of 99mTc-sestamibi., Methods: We measured clearance rates of 99mTc-tetrofosmin in four healthy smokers and four healthy nonsmokers and of 99mTc-sestamibi in six otherwise healthy patients with psoriasis before and after 2 weeks of therapy with cyclosporine A (2.5-5 mg/kg/day) and two healthy women taking the oral contraceptive pill, as both cyclosporine and steroids are known to be P-gp modulators., Results: The clearance rate of 99mTc-tetrofosmin in nonsmokers ranged from 0.38 to 0.63%/min, similar to the previously recorded rate for 99mTc-sestamibi [0.43 (SD 0.083)%/min], but it was not delayed in smokers (range 0.42-0.97%/min). Cyclosporine had no significant effect on 99mTc-sestamibi clearance, although clearance rates in the two women taking the oral contraceptive pill were both fast (0.58 and 0.62%/min)., Conclusion: Although the role of P-gp expression in the clearance of 99mTc-sestamibi remains unproven, we conclude that 99mTc-tetrofosmin is not as P-gp-avid as 99mTc-sestamibi. A role for P-gp expression in the clearance of 99mTc-sestamibi remains unproven. Higher doses of P-gp inhibitors will be required and clearance rates correlated with immunohistochemical expression of P-gp.

What Is Already Known About This Subject: * Very little is known about the physiology of P-glycoprotein (P-gp) expression in the lungs. * Ex vivo evidence based on resected lung tissue suggests that pulmonary P-gp is upregulated by cigarette smoke, but there are no in vivo studies to date., What This Study Adds: * The novel observation that healthy cigarette smokers have a delayed pulmonary elimination rate of inhaled (99m)Tc-sestamibi, a P-gp substrate, provides for the first time a potential method for quantifying functional pulmonary P-gp expression that may inform about drug therapy by inhalation as well as provide a non-invasive, quantitative, human biomarker for assessing P-gp modulators., Aim: To explore inhaled technetium-99m-labelled hexakis-methoxy-isobutyl isonitrile ((99m)Tc-sestamibi) for quantifying pulmonary P-glycoprotein (P-gp) expression., Methods: The elimination rate from the lungs of (99m)Tc-sestamibi was recorded scintigraphically for 30 min following inhalation as an aerosol in healthy smokers, nonsmokers and patients with lung disease., Results: (99m)Tc-sestamibi elimination rates [% min(-1) (SD; P vs. healthy nonsmokers)] were: healthy nonsmokers, 0.43 (0.083); healthy smokers, 0.19 (0.056; P < 0.001); chronic obstructive pulmonary disease patients, 0.26 (0.077; P < 0.001). Elimination rates in three patients with interstitial lung disease were not accelerated., Conclusion: Cigarette smoke upregulates lung P-gp. (99m)Tc-sestamibi elimination in normal smokers could be used to test new P-gp modulators. The findings also have implications for inhaled drug delivery.

Purpose: Whole-body gamma camera counting is an alternative to faecal 111In collection for quantifying disease activity in inflammatory bowel disease (IBD) but requires administration of imaging activities of 111In. The aim of this study was to explore a dedicated whole-body counter which requires 20-fold less activity than gamma camera counting., Methods: Thirty patients with known or suspected IBD received 99mTc-granulocytes (approximately 200 MBq) and 111In-granulocytes (approximately 0.5 MBq). The 99mTc-cells were injected 45 min after the 111In-cells and immediately after a baseline 111In whole-body count. The decay-corrected count at 120 h was expressed as a fraction of baseline to give whole-body 111In retention (WBR). One patient was excluded as the injected cells were non-viable., Results: Median 45-min intravascular 111In recovery was 35% in patients compared with 43% in six normal volunteers (p<0.05). WBR in normals ranged from 91% to 93% and in 11 patients with negative 99mTc imaging from 87% to 96%. Only one of 11 patients with negative imaging had WBR <90% while 11/12 patients with WBR <90% had abnormal imaging. Ten of 13 patients with Crohn's disease (CD) had abnormal imaging. The lowest WBR in these ten was 77% and six had values of >90%. There was a significant association between WBR and 99mTc image grade (Rs=0.73, p<0.002) in 16 patients without CD, but not in 13 patients with CD (Rs=0.54, p>0.05)., Conclusion: Dedicated whole-body counting is able to quantify disease activity in IBD but may give normal values in active CD.