Molecular radiotheranostics for neuroendocrine tumours

This article discusses the important role of nuclear medicine imaging and therapy in the management of neuroendocrine tumours (NETs). Somatostatin receptor scintigraphy has a high impact on patient management versus conventional imaging. Molecular radiotherapy is an important part of the management of patients with NETs. Selection of patients for molecular radiotherapy in NETs is based on uptake on their radionuclide imaging study. The imaging agent has the same mechanism of uptake as the therapeutic agent. Thus, the imaging study preselects patients that are likely to concentrate radiation within their tumours

The Scherk-Schwarz mechanism as a flux compactification with internal torsion

The aim of this paper is to make progress in the understanding of the Scherk-Schwarz dimensional reduction in terms of a compactification in the presence of background fluxes and torsion. From the eleven dimensional supergravity point of view, we find that a general E6(6) S-S phase may be obtained by turning on an appropriate background torsion, together with suitable fluxes, some of which can be directly identified with certain components of the four-form field-strength. Furthermore, we introduce a novel (four dimensional) approach to the study of dualities between flux/torsion compactifications of Type II/M-theory. This approach defines the action that duality should have on the background quantities, in order for the E7(7) invariance of the field equations and Bianchi identities to be restored also in the presence of fluxes/torsion. This analysis further implies the interpretation of the torsion flux as the T-dual of the NS three-form flux.Comment: Version published on J. High Energy Phy

Setting up a quantitative SPECT imaging network for a European multi-centre dosimetry study of radioiodine treatment for thyroid cancer as part of the MEDIRAD project

Background: Differentiated thyroid cancer has been treated with radioiodine for almost 80 years, although controversial questions regarding radiation-related risks and the optimisation of treatment regimens remain unresolved. Multi-centre clinical studies are required to ensure recruitment of sufficient patients to achieve the statistical significance required to address these issues. Optimisation and standardisation of data acquisition and processing are necessary to ensure quantitative imaging and patient-specific dosimetry. Material and methods: A European network of centres able to perform standardised quantitative imaging of radioiodine therapy of thyroid cancer patients was set-up within the EU consortium MEDIRAD. This network will support a concurrent series of clinical studies to determine accurately absorbed doses for thyroid cancer patients treated with radioiodine. Five SPECT(/CT) systems at four European centres were characterised with respect to their system volume sensitivity, recovery coefficients and dead time. Results: System volume sensitivities of the Siemens Intevo systems (crystal thickness 3/8″) ranged from 62.1 to 73.5 cps/MBq. For a GE Discovery 670 (crystal thickness 5/8″) a system volume sensitivity of 92.2 cps/MBq was measured. Recovery coefficients measured on three Siemens Intevo systems show good agreement. For volumes larger than 10 ml, the maximum observed difference between recovery coefficients was found to be ± 0.02. Furthermore, dead-time coefficients measured on two Siemens Intevo systems agreed well with previously published dead-time values. Conclusions: Results presented here provide additional support for the proposal to use global calibration parameters for cameras of the same make and model. This could potentially facilitate the extension of the imaging network for further dosimetry-based studies

Dosimetry-based treatment for Graves' disease.

Objective The aim of this retrospective study was to assess the long-term outcome of a personalized dosimetry approach in Graves' disease aiming to render patients euthyroid from a planned thyroid absorbed dose of 60 Gy.Patients and methods A total of 284 patients with Graves' disease were followed prospectively following administration of radioiodine calculated to deliver an absorbed dose of 60 Gy. Patients with cardiac disease were excluded. Outcomes were analysed at yearly intervals for up to 10 years with a median follow-up of 37.5 months.Results A single radioiodine administration was sufficient to render a patient either euthyroid or hypothyroid in 175 (62%) patients, the remainder requiring further radioiodine. The median radioactivity required to deliver 60 Gy was 77 MBq. Less than 2% patients required 400-600 MBq, the standard activity administered in many centres. In the cohort receiving a single administration, 38, 32 and 26% were euthyroid on no specific thyroid medication at 3, 5 and 10 years, respectively. Larger thyroid volumes were associated with the need for further therapy. The presence of nodules on ultrasonography did not adversely affect treatment outcome.Conclusion A personalized dosimetric approach delayed the long-term onset of hypothyroidism in 26% of patients. This was achieved using much lower administered activities than currently recommended. Future studies will aim to identify those patients who would benefit most from this approach

Objective comparison of lesion detectability in low and medium-energy collimator iodine-123 mIBG images using a channelized Hotelling observer.

Iodine-123 mIBG imaging is widely regarded as a gold standard for diagnostic studies of neuroblastoma and adult neuroendocrine cancer although the optimal collimator for tumour imaging remains undetermined. Low-energy (LE) high-resolution (HR) collimators provide superior spatial resolution. However due to septal penetration of high-energy photons these provide poorer contrast than medium-energy (ME) general-purpose (GP) collimators. LEGP collimators improve count sensitivity. The aim of this study was to objectively compare the lesion detection efficiency of each collimator to determine the optimal collimator for diagnostic imaging. The septal penetration and sensitivity of each collimator was assessed. Planar images of the patient abdomen were simulated with static scans of a Liqui-Phil™ anthropomorphic phantom with lesion-shaped inserts, acquired with LE and ME collimators on 3 different manufacturers' gamma camera systems (Skylight (Philips), Intevo (Siemens) and Discovery (GE)). Two-hundred normal and 200 single-lesion abnormal images were created for each collimator. A channelized Hotelling observer (CHO) was developed and validated to score the images for the likelihood of an abnormality. The areas under receiver-operator characteristic (ROC) curves, Az, created from the scores were used to quantify lesion detectability. The CHO ROC curves for the LEHR collimators were inferior to the GP curves for all cameras. The LEHR collimators resulted in statistically significantly smaller Azs (p  123I mIBG image lesion detectability over LEHR collimators that provided better spatial resolution

Superconception in mammalian pregnancy can be detected and increases reproductive output per breeding season

The concept of superfetation, a second conception during pregnancy, has been controversial for a long time. In this paper we use an experimental approach to demonstrate that female European brown hares (Lepus europaeus) frequently develop a second pregnancy while already pregnant and thereby increase their reproductive success. After a new, successful copulation, we confirmed additional ovulations before parturition in living, late-pregnant females by detecting a second set of fresh corpora lutea using high-resolution ultrasonography. The presence of early embryonic stages in the oviduct, demonstrated by oviduct flushing, next to fully developed fetuses in the uterus is best explained by passage of semen through the late-pregnant uterus; this was confirmed by paternity analysis using microsatellite profiling. Subsequent implantation occurred after parturition. This superfetation, categorized as superconception, significantly increased litter size and permitted females to produce up to 35.4% more offspring per breeding season. It is therefore most likely an evolutionary adaptation

Can starling eggs be useful as a biomonitoring tool to study organohalogenated contaminants on a worldwide scale

Large-scale international monitoring studies are important to assess emission patterns and environmental distributions of organohalogenated contaminants (OHCs) on a worldwide scale. In this study, the presence of OHCs was investigated on three continents (Europe, North America and Australasia), using eggs of starlings (Sturnus vulgaris and Sturnus unicolor) to assess their suitability for large-scale monitoring studies. To the best of our knowledge, this is the first study using bird eggs of the same species as a biomonitor for OHCs on an intercontinental scale. We found significant differences in OHC concentrations of the eggs among sampling locations, except for hexachlorocyclohexanes (HCHs). Mean concentrations of sum polychlorinated biphenyls (PCBs) in eggs ranged from 78 ± 26 ng/g lipid weight (lw) in Australia to 2900 ± 1300 ng/g lw in the United States. The PCB profile was dominated by CB 153 and CB 138 in all locations, except for New Zealand, where the contribution of CB 95, CB 101 and CB 149 was also high. The highest mean sum polybrominated diphenyl ether (PBDE) concentrations were found in Canada (4400 ± 830 ng/g lw), while the lowest mean PBDE concentrations were measured in Spain (3.7 ± 0.1 ng/g lw). The PBDE profile in starling eggs was dominated by BDE 47 and BDE 99 in all countries, but in Belgium, the higher brominated PBDEs had a higher contribution compared to other countries. For the organochlorine pesticides (OCPs), dichlorodiphenyltrichloroethanes (DDTs) ranged from 110 ± 16 ng/g lw in France to 17,000 ± 3400 ng/g lw in New Zealand, while HCHs and hexachlorobenzene were generally in low concentrations in all sampling locations. Chlordanes were remarkably high in eggs from the United States (2500 ± 1300 ng/g lw). The OCP profile in all countries was largely dominated by p,p′-DDE. In general, the worldwide trends we observed in starling eggs were in accordance with the literature on human and environmental OHC data, which suggests that there is potential for using starling eggs as a biomonitoring tool on a large geographical scale. This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed

Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma.

Objective Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) therapy is an established treatment modality for relapsed/refractory neuroblastoma, most frequently administered according to fixed or weight-based criteria. We evaluate response and toxicity following a dosimetry-based, individualized approach.Materials and methods A review of 44 treatments in 25 patients treated with I-mIBG therapy was performed. Patients received I-mIBG therapy following relapse (n=9), in refractory disease (n=12), or with surgically unresectable disease despite conventional treatment (n=4). Treatment schedule (including mIBG dose and number of administrations) was individualized according to the clinical status of the patient and dosimetry data from either a tracer study or previous administrations. Three-dimensional tumour dosimetry was also performed for eight patients.Results The mean administered activity was 11089±7222 MBq and the mean whole-body dose for a single administration was 1.79±0.57 Gy. Tumour-absorbed doses varied considerably (3.70±3.37 mGy/MBq). CTCAE grade 3/4 neutropenia was documented following 82% treatments and grade 3/4 thrombocytopenia following 71% treatments. Further acute toxicity was found in 49% of patients. All acute toxicities resolved with appropriate therapy. The overall response rate was 58% (complete or partial response), with a further 29% of patients having stable disease.Conclusion A highly personalized approach combining patient-specific dosimetry and clinical judgement enables delivery of high activities that can be tolerated by patients, particularly with stem cell support. We report excellent response rates and acceptable toxicity following individualized I-mIBG therapy