Supplementary Figure S1; Supplementary Table S1.

INTRODUCTION:TROG 09.03 prospectively studied the utility of Fluorine-18 Fluorodeoxyglucose (18-FDG) PET in the management of Merkel cell carcinoma of skin.METHODS:Following consent and registration, a pre-treatment FDG-PET/CT was performed. Sites of avid disease were confirmed by cytology where practicable. Following surgery, patients with AJCCv7 Stages IIA-IIIB disease were treated with chemo-radiotherapy and reassessed with a post-treatment PET.RESULTS:Fifty-eight subjects (45 males and 13 females, median age 68 years) were enrolled between 2011 and 2015, 43 patients of whom went on to receive chemo-radiotherapy. An occult primary was present in 22 (37.9%), T1 in 22 (37.9%) and T2 disease in 14 (24.1%). Nodal disease was present in 69% of cases. Fifty per cent of subjects had gross residual disease at the primary site and/or nodal site at the time of registration. 18-FDG PET/CT had a sensitivity of 94.74% (95% CI 82-99.3%) and a specificity of 88.24% (95% CI 63.56-98.54). The positive predictive value was 94.74% (83.01-98.51) and the negative predictive value was 88.24% (95% CI 65.81-96.69). The pre-treatment PET influenced a treatment decision in 27.6% of cases. Upstaging occurred in 15 (25.9%), with no down staging. Other diseases were identified in 4 (6.9%) patients. Univariate analysis failed to demonstrate that pre-treatment SUV levels or a negative post-treatment PET had any impact on overall survival. PET staged patients had 89% 3-year in-field loco-regional control and 76% 3-year overall survival.CONCLUSION:Staging 18-FDG-PET significantly influenced treatment decisions in approximately one-third of cases of MCC and should be considered in the routine pre-treatment work-up. Post-treatment PET was not found to be prognostic. Funding through the Medicare Benefits Schedule needs to be considered for high risk MCC.

This study identified an appropriate engineering model which described the exchange kinetics of sodium ions with a strong acid cation resin. Synthetic resins have potential application for the demineralization of coal seam (CS) water prior to beneficial reuse. However, there is limited data regarding the kinetic behaviour of strong acid cation (SAC) resin for the removal of sodium ions, the most prevalent ions in the water collected from coal seams (produced water) during natural gas extraction. In particular, exchange kinetics need to be understood in relation to estimating how full scale columns of resin may perform. Kinetic analysis revealed that the exchange of sodium ions from both sodium chloride and sodium bicarbonate solutions with SAC resin reached equilibrium within minutes at ambient temperature. Optimal simulation of the kinetic data for both chloride and bicarbonate containing solutions was achieved by application of the Brouers, Weron and Sotolongo (BWS) fractal equation; and this should be used as the basis for development of an engineering model. The model parameters varied depending upon the ratio of resin to liquid employed in the tests, with rates showing substantial enhancement once an excess of resin exchange sites were present. The exchange process was apparently controlled in part by intraparticle diffusion, with three phases inferred for sodium chloride solutions and two for sodium bicarbonate solutions. Other rate limiting phenomena such as film diffusion appeared to play a role under certain conditions.

OBJECTIVE:Damage to the blood-brain barrier (BBB) is an important secondary mechanism that occurs following traumatic brain injury (TBI) and may provide a potential therapeutic target to improve patient outcome. For such a progress to be realised, an accurate assessment of BBB compromise needs to be established.METHODS:Fourteen patients with TBI were prospectively recruited. Post-traumatic BBB dysfunction was assessed using dynamic contrast-enhanced MRI (DCE-MRI), single-photon emission computerised tomography (SPECT) and serum S100B levels.RESULTS:A statistically significant correlation between standardised uptake value ratio (SUVR) calculated from 99mTc-DTPA SPECT and K(trans) (a volume transfer constant) from DCE-MRI was found for those eight patients who had concurrent scans. The positive correlation persisted when the data were corrected for patient age, number of days following trauma and both parameters combined. We found no statistically significant correlation between either of the imaging modalities and concurrent serum S100B levels.DISCUSSION:The correlation of SPECT with DCE-MRI suggests that either scan may be used to assess post-traumatic BBB damage. We could not support serum S100B to be an accurate measure of BBB damage when sampled a number of days following injury but the small number of patients, the heterogeneity in TBI patients and the delay following injury makes any firm conclusions regarding S100B and BBB difficult.

BACKGROUND:The role of fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) scanning in operable pancreas cancer is unclear. We, therefore, wanted to investigate the impact of PET/CT on management, by incorporating it into routine work-up.METHODS:This was a single-institution prospective study. Patients with suspected and potentially operable pancreas, distal bile duct or ampullary carcinomas underwent PET/CT in addition to routine work-up. The frequency that PET/CT changed the treatment plan or prompted other investigations was determined. The distribution of standard uptake values (SUV) among primary tumours, and adjacent to biliary stents was characterised.RESULTS:Fifty-six patients were recruited. The surgical plan was abandoned in 9 (16%; 95% CI: 6-26) patients as a result of PET/CT identified metastases. In four patients, metastases were missed and seven were inoperable at surgery, not predicted by PET/CT. Unexpected FDG uptake resulted in seven additional investigations, of which two were useful. Among primary pancreatic cancers, a median SUV was 4.9 (range 2-12.1). SUV was highest around the biliary stent in 17 out of 28 cases. PET/CT detected metastases in five patients whose primary pancreatic tumours demonstrated mild to moderate avidity (SUV < 5).CONCLUSIONS:PET/CT in potentially operable pancreas cancer has limitations. However, as a result of its ability to detect metastases, PET/CT scanning is a useful tool in the selection of such patients for surgery.

This paper reports a study of ion exchange (IX) as an alternative CSG water treatment to the widely used reverse osmosis (RO) desalination process. An IX pilot plant facility has been constructed and operated using both synthetic and real CSG water samples. Application of appropriate synthetic resin technology has proved the effectiveness of IX processes.

Gallium-68 ((68) Ga)-labelled somatostatin analogue imaging by positron emission tomography (PET) is increasingly replacing single photon (such as (111) In-labelled octreotide) imaging in the detection and staging of carcinoid and other neuroendocrine tumours. Among other tissues, pituitary uptake of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate (DOTA-TATE) and other somatostatin analogues is physiological. DOTA-TATE also accumulates in meningiomas, which have a high density of somatostatin receptor expression. The combination of pituitary and skull base meningioma uptake results in a characteristic 'double hot spot' appearance, which indicates the presence of a meningioma. This is a case of a middle-aged woman who underwent (68) Ga-DOTA-TATE PET for confirmation and staging of clinically suspected carcinoid tumour, in whom a skull base meningioma was incidentally discovered. With the increasing use of PET in the management of neuroendocrine tumours - and the not infrequent occurrence of meningiomas - the appearance of meningiomas on somatostatin analogue imaging should be one with which reporting clinicians are familiar.

e13128 Background: Immunotherapy strategies using antigen loaded dendritic cells are being widely utilized in clinical trials for patients with malignancies. To induce effective immune responses against tumors, dendritic cells need to traffic into areas rich in immune effector cells such as T cells and natural killer T cells. In our study, we investigated localization of monocyte derived dendritic cells (MoDC) following different routes of administration, and whether cryopreservation or type of antigen has an impact on MoDC trafficking properties. Methods: Twelve patients with metastatic malignancies received 111Indium-oxine labeled MoDC pulsed with peptide/protein based antigen or glycolipid antigen, which was administered intradermally, subcutaneously or intravenously, and fresh or after a cryopreservation step. Results: Following intravenous administration, MoDC rapidly distributed into lungs, followed by liver and spleen. In nine of twelve cases intradermally administered MoDC migrated to regional lymph nodes but this was true only for one of nine MoDC injections administered subcutaneously. Cryopreservation and type of antigen did not influence migration capabilities of MoDC. Conclusions: Our data confirms that MoDC trafficking is markedly dependent on the mode of delivery. There is no difference in trafficking of MoDC administered fresh or after cryopreservation and the type of antigen does not have impact on MoDC distribution in the human body.

Abstract Purpose: Assessing clinical activity of molecularly targeted anticancer agents, especially in the absence of tumor shrinkage, is challenging. To evaluate on-treatment 18F-fluorodeoxyglucose (FDG) and/or 18F-fluorodeoxythymidine (FLT) positron emission tomography (PET) for this purpose, we conducted a prospective multicenter trial assessing PET response rates and associations with progression-free (PFS) and overall survival (OS) in 2nd/3rd-line non–small-cell lung cancer patients treated with erlotinib. Experimental Design: PET/computed tomography (CT) scans were conducted at baseline, day (d)14 and d56 after the first daily erlotinib dose, with diagnostic CT at baseline and d56 (all scans centrally reviewed). PET partial metabolic response (PMR) was defined as a mean decrease (in ≤5 lesions/patient) of 15% or more maximum standardized uptake value. PFS was investigator-determined. Results: Of 74 erlotinib-treated patients, 51 completed all imaging assessments through d56; 13 of 51 (26%) FDG-evaluable patients had PMR at d14, as did 9 of 50 (18%) FLT-evaluable patients. Four (7.8%) showed partial responses (PR) by d56 CT; all 4 had PMR by d14 FDG-PET with 3 PMRs by d14 FLT-PET. Three of the 4 patients with CT PR had evaluable archival tumor tissue; all 3 had epidermal growth factor receptor mutations. D14 and d56 PMRs by FDG or FLT were associated with improved PFS; HRs for PET responders versus nonresponders were 0.3 to 0.4. D14 FDG-PET PMR was associated with improved OS (P = 0.03) compared with FDG-PET nonresponders. Conclusion: Early (d14) FDG-PET PMR is associated with improved PFS and OS, even in the absence of subsequent Response Evaluation Criteria in Solid Tumors response. These data support inclusion of FDG-PET imaging in clinical trials testing novel targeted therapies, particularly those with anticipated cytostatic effects. Clin Cancer Res; 17(10); 3304–15. ©2011 AACR.

The Response Evaluation Criteria in Solid Tumors (RECIST) are widely used but have recognized limitations. Molecular imaging assessments, including changes in 18F-deoxyglucose (FDG) or 18F-deoxythymidine (FLT) uptake by positron emission tomography (PET), may provide earlier, more robust evaluation of treatment efficacy.

PET-MRI fusion is widely used in oncology for early tumour diagnosis, localisation and monitoring of therapy effects. Automatic extraction of the lesions on PET images is desirable, but remains problematic. Manual segmentation of PET images is time consuming, and restricts the definition of the tumour extent to some arbitrary threshold. This can be sub-optimal in brain tumour for instance, where tumour is diffused by nature. Moreover, when the tracer uptake is not limited to the invaded regions, it becomes more difficult for an expert to define a precise contour. In this work, we propose a soft segmentation approach to automatically segment brain tumours in 18F-FDOPA PET images using a tumour growth model. This is based on extrapolating the tumour extent starting from tumour boundaries extracted from T1W MRI. A reaction-diffusion model is utilised for the extrapolation task to obtain tumour probability density. We evaluate our method on patient's PET/MRI images. The advantage of this method is that it is completely automatic and offers a soft segmentation of tumours in PET images.

RATIONALE We report a new method to diagnose acute pulmonary embolism (PE) by single photon emission computerized tomography (SPECT) after administration of (99m)Tc-labeled anti-D-dimer (DI-80B3) monoclonal antibody Fab' fragments. This novel technique provides an additional approach to diagnosing PE in patients for whom other methods are nondiagnostic or contraindicated. OBJECTIVES We performed a prospective, multicenter study to investigate the sensitivity and specificity of (99m)Tc-DI-80B3/SPECT in patients with suspected acute PE. METHODS Subjects with a moderate to high clinical probability of PE or a positive D-dimer test underwent a PE-protocol contrast-enhanced multidetector thoracic computed tomography (CT) scan as well as (99m)Tc-DI-80B3/SPECT (0.5 mg (99m)Tc-DI-80B3 intravenously followed by a thoracic SPECT 2.5 h later). Separate and independent adjudication committees, blinded to clinical data and other test results, interpreted the (99m)Tc-DI-80B3/SPECT scans (PE detected as foci of abnormally increased (99m)Tc uptake) and the thoracic CT scans using Prospective Investigation of Pulmonary Embolism Diagnosis II criteria. MEASUREMENTS AND MAIN RESULTS Of the 52 patients who were enrolled and completed both tests, 42 had both evaluable SPECT scans and thoracic CT scans. Using the criterion standard (thoracic CT scan) there were 21 patients with PE and 21 without. (99m)Tc-DI-80B3/SPECT had a sensitivity of 76.2% (95% confidence interval, 52.8-91.8%) and a specificity of 90.5% (95% confidence interval, 69.8-98.8%). Treatment-related serious adverse events did not occur. CONCLUSIONS (99m)Tc-DI-80B3/SPECT was sensitive and specific for acute PE in subjects with moderate to high clinical probability of PE or a positive D-dimer test. (99m)Tc-DI-80B3/SPECT demonstrated an acceptable safety profile and avoids exposure to contrast.

Objectives: Pre-clinical experiments demonstrated that intravenous Tc-99m labelled DI-DD-3B6/22-80B3 humanised antifibrin-D-dimer Fab' fragments (Tc-99m-DI-80B3) allowed scintigraphic imaging of acute pulmonary emboli (PE). The aims of this clinical study were to determine the safety of Tc-99m-DI-80B3 in patients with PE and evaluate the resulting scintigraphic images for the localisation of acute PE.Materials/patients and methods: Tc-99m-DI-80133 (0.5 mg, 710-850 MBq) was administered intravenously to subjects (n = 14) with segmental or larger PE on recent contrast-enhanced helical CT scans. Thoracic SPECT scans were acquired 15 minutes, 2 hours and 4 hours afterwards. Subjects were followed for 90 days subsequently.Results: There were no serious adverse events or antibody responses associated with Tc-99m-DI-80B3 administration. Focal accumulations of Tc-99m-DI-80B3 on the SPECT images of the thorax acquired at four hours corresponded to pulmonary emboli detected by CT. Two independent "blinded" SPECT readers identified 79% and 71% (respectively) of the right lung and 79% and 64% (respectively) of the left lung in which CT scans disclosed PE.Conclusions: Tc-99m-DI-80B3 is well-tolerated in patients with acute PE and does not induce an immune response. Tc-99m-DI-80B3 may offer a novel approach to imaging PE in a clinically acceptable timeframe without exposure to potentially nephrotoxic radiographic contrast agents. (Heart, Lung and Circulation 2011; 20:503-511) (C) 2011 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved.