Spect perfusion imaging versus CT for predicting radiation injury to normal lung in lung cancer patients.

Objectives In non-small cell lung cancer (NSCLC) patients, to establish whether the fractional volumes of irradiated anatomic or perfused lung differed between those with and without deteriorating lung function or radiation associated lung injury (RALI).Methods 48 patients undergoing radical radiotherapy for NSCLC had a radiotherapy-planning CT scan and single photon emission CT lung perfusion imaging (99mTc-labelled macroaggregate albumin). CT defined the anatomic and the single photon emission CT scan (co-registered with CT) identified the perfused (threshold 20 % of maximum) lung volumes. Fractional volumes of anatomic and perfused lung receiving more than 5, 10, 13, 20, 30, 40, 50 Gy were compared between patients with deteriorating (>median decline) vs stable (vs stable FEV1 ( p = 0.005, 0.005 and 0.025 respectively) but did not differ for higher doses of radiation (>30, 40, 50 Gy). Fractional volumes of anatomic and perfused lung receiving > 10 Gy best predicted decline in FEV1 (Area under receiver operating characteristic curve (Az = 0.77 and 0.76 respectively); sensitivity/specificity 75%/81 and 80%/71%) for a 32.7% anatomic and 33.5% perfused volume cut-off. Irradiating an anatomic fractional volume of 4.7% to > 50 Gy had a sensitivity/specificity of 83%/89 % for indicating RALI (Az = 0.83).Conclusion A 10-20 Gy radiation dose to anatomic or perfused lung results in decline in FEV1. A fractional anatomic volume of >5% receiving >50 Gy influences development of RALI.Advances in knowledge Extent of low-dose radiation to normal lung influences functional respiratory decline

Compartmental Model for ²²³Ra-Dichloride in Patients With Metastatic Bone Disease From Castration-Resistant Prostate Cancer.

Purpose223Ra-Dichloride is used for treatment of patients with metastatic bone disease from castration-resistant prostate cancer. The uptake and mechanism of action of 223Ra-Dichloride is not well understood. The aim of this work was to develop a compartmental model for 223Ra-Dichloride in patients to improve understanding of the underlying mechanisms.Methods and materialsA compartmental model was developed based on activity retention data from 6 patients (2 treatments of 110 kBq/kg 223Ra-Dichloride) for plasma, bone surfaces, small intestines, large intestines, and excretion data. Rate constants were extracted. Rate constant variability between patients and treatments was assessed. A population model was proposed and compared with the established International Commission on Radiological Protection-67 compartmental model.ResultsA single bone compartment cannot accurately describe activity retention in the skeleton. The addition of a second bone compartment improved the fit to skeleton retention data, and the Akaike information criterion decreased. Mean rate constants of 4.0 (range, 1.9-10.9) and 0.15 (0.07-0.39) h-1 were obtained for transport from plasma to first bone compartment and vice versa. Rate constants from first to second bone compartment and back of 0.03 (0.02-0.06) and 0.008 (0.003-0.011) h-1 were calculated. Rate constants for individual patients showed no significant difference between patients and treatments.ConclusionsThe developed compartmental model suggests that 223Ra-Dichloride initially locates at the bone surface and is then incorporated into the bone matrix relatively quickly. This observation could have implications for dosimetry and understanding of the effects of alpha radiation on normal bone tissue. Results suggest that a population model based on patient measurements is feasible

Abdo-Man: a 3D-printed anthropomorphic phantom for validating quantitative SIRT.

Background The use of selective internal radiation therapy (SIRT) is rapidly increasing, and the need for quantification and dosimetry is becoming more widespread to facilitate treatment planning and verification. The aim of this project was to develop an anthropomorphic phantom that can be used as a validation tool for post-SIRT imaging and its application to dosimetry.Method The phantom design was based on anatomical data obtained from a T1-weighted volume-interpolated breath-hold examination (VIBE) on a Siemens Aera 1.5 T MRI scanner. The liver, lungs and abdominal trunk were segmented using the Hermes image processing workstation. Organ volumes were then uploaded to the Delft Visualization and Image processing Development Environment for smoothing and surface rendering. Triangular meshes defining the iso-surfaces were saved as stereo lithography (STL) files and imported into the Autodesk® Meshmixer software. Organ volumes were subtracted from the abdomen and a removable base designed to allow access to the liver cavity. Connection points for placing lesion inserts and filling holes were also included. The phantom was manufactured using a Stratasys Connex3 PolyJet 3D printer. The printer uses stereolithography technology combined with ink jet printing. Print material is a solid acrylic plastic, with similar properties to polymethylmethacrylate (PMMA).Results Measured Hounsfield units and calculated attenuation coefficients of the material were shown to also be similar to PMMA. Total print time for the phantom was approximately 5 days. Initial scans of the phantom have been performed with Y-90 bremsstrahlung SPECT/CT, Y-90 PET/CT and Tc-99m SPECT/CT. The CT component of these images compared well with the original anatomical reference, and measurements of volume agreed to within 9 %. Quantitative analysis of the phantom was performed using all three imaging techniques. Lesion and normal liver absorbed doses were calculated from the quantitative images in three dimensions using the local deposition method.Conclusions 3D printing is a flexible and cost-efficient technology for manufacture of anthropomorphic phantom. Application of such phantoms will enable quantitative imaging and dosimetry methodologies to be evaluated, which with optimisation could help improve outcome for patients

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

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

EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations.

A framework is proposed for modelling the uncertainty in the measurement processes constituting the dosimetry chain that are involved in internal absorbed dose calculations. The starting point is the basic model for absorbed dose in a site of interest as the product of the cumulated activity and a dose factor. In turn, the cumulated activity is given by the area under a time-activity curve derived from a time sequence of activity values. Each activity value is obtained in terms of a count rate, a calibration factor and a recovery coefficient (a correction for partial volume effects). The method to determine the recovery coefficient and the dose factor, both of which are dependent on the size of the volume of interest (VOI), are described. Consideration is given to propagating estimates of the quantities concerned and their associated uncertainties through the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and its associated uncertainty. This approach is demonstrated in a clinical example

InfuShield: a shielded enclosure for administering therapeutic radioisotope treatments using standard syringe pumps.

The administration of radionuclide therapies presents significant radiation protection challenges. The aim of this work was to develop a delivery system for intravenous radioisotope therapies to substantially moderate radiation exposures to staff and operators. A novel device (InfuShield) was designed and tested before being used clinically. The device consists of a shielded enclosure which contains the therapeutic activity and, through the hydraulic action of back-to-back syringes, allows the activity to be administered using a syringe pump external to the enclosure. This enables full access to the pump controls while simultaneously reducing dose to the operator. The system is suitable for use with all commercially available syringe pumps and does not require specific consumables, maximising both the flexibility and economy of the system. Dose rate measurements showed that at key stages in an I mIBG treatment procedure, InfuShield can reduce dose to operators by several orders of magnitude. Tests using typical syringes and infusion speeds show no significant alteration in administered flow rates (maximum of 1.2%). The InfuShield system provides a simple, safe and low cost method of radioisotope administration

Characterisation of a CZT detector for dosimetry of molecular radiotherapy

A pixelated cadmium zinc telluride (CZT) detector has been characterised for the purpose of developing a quantitative single photon emission computed tomography (SPECT) system for dosimetry of molecular radiotherapy (MRT). This is the aim of the Dosimetric Imaging with CZT (DEPICT) project, which is a collaboration between the University of Liverpool, The Royal Marsden Hospital, The Royal Liverpool and Broadgreen University Hospital, and the commercial partner Kromek. CZT is a direct band gap semiconductor with superior energy resolution and stopping power compared to scintillator detectors used in current SPECT systems. The inherent detector properties have been investigated and operational parameters such as bias voltage and peaking time have been selected to optimise the performance of the system. Good energy resolution is required to discriminate γ-rays that are scattered as they are emitted from the body and within the collimator, and high photon throughput is essential due to the high activities of isotopes administered in MRT. The system has an average measured electronic noise of 3.31 keV full width at half maximum (FWHM), determined through the use of an internal pulser. The energy response of the system was measured across the energy region of interest 59.5 keV to 364.5 keV and found to be linear. The reverse bias voltage and peaking time producing the optimum FWHM and maximum photon throughput were 600 V and 0.5 μs respectively. The average dead time of the system was measured as 4.84 μs and charge sharing was quantified to be 0.71 % at 59.5 keV . A pixel sensitivity calibration map was created and planar images of the medical imaging isotopes 99mTc and 123I were acquired by coupling the device to a prototype collimator, thereby demonstrating the suitability of the detector for the DEPICT project

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

Imaging and dosimetry for radium-223: the potential for personalized treatment.

Radium-223 ( 223 Ra) offers a new option for the treatment of bone metastases from prostate cancer. As cancer treatment progresses towards personalization, the potential for an individualized approach is exemplified in treatments with radiotherapeutics due to the unique ability to image in vivo the uptake and retention of the therapeutic agent. This is unmatched in any other field of medicine. Currently, 223 Ra is administered according to standard fixed administrations, modified according to patient weight. Although gamma emissions comprise only 1% of the total emitted energy, there are increasing reports that quantitative imaging is feasible and can facilitate patient-specific dosimetry. The aim of this article is to review the application of imaging and dosimetry for 223 Ra and to consider the potential for treatment optimization accordingly, in order to ensure clinical and cost effectiveness of this promising agent