Quantitative Imaging: A hospital physicist s perspective James Scuffham

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1 Quantitative Imaging: A hospital physicist s perspective James Scuffham Clinical Scientist, Royal Surrey County Hospital NHS Foundation Trust Associate Tutor, University of Surrey

2 Background The Royal Surrey is a District General Hospital in South East England serving a population of 320,000. It incorporates St Luke s Cancer Centre, which serves a population of 1.2 million for cancer services

3 Background The Nuclear Medicine department at RSCH has three gamma cameras (1 SPECT/CT), and two ward rooms for molecular radiotherapy Nuc Med is supported by a team of 8 physicists who also provide Medical Physics support to a further 7 diagnostic imaging departments and 5 mobile PET/CT units. Molecular Radiotherapy Procedures at RSCH include: I-131 for thyroid cancer I-131 for thyrotoxicosis Ra-223 for skeletal metastases from prostate cancer Y-90 microspheres for hepatic malignancies Lu-177 DOTATATE for neuroendocrine cancer [Y-90 radiosynoviorthesis] [Sr-89 / Sm-153 for painful bone metastases]

4 Why am I here? RSCH was a collaborator on MetroMRT and is an unfunded clinical partner in MRTDosimetry We have two joint PhD students with NPL and the University of Surrey University of Surrey is a strategic partner with NPL

5 But what about dosimetry? My confession. Routine organ-level dosimetry is not done at RSCH (except for Y-90 microspheres). But. We are striving towards it. Barriers? Lack of clinical interest/confidence (no trial evidence) Lack of guidelines on how to do it properly Gamma camera availability Logistics (patient transfer; staff dose concerns) Time Cost / Reimbursement

6 What about quantitative imaging? We have established quantitative imaging protocols for: Lu-177 (through Jill Merrett s PhD and MetroMRT) and I-131 (through the SELIMETRY study)

7 I-131: The SELIMETRY Study Multi-centre trial in the UK assessing the efficacy of selumetinib followed by radioiodine in iodine refractory thyroid cancer. Ho et al, NEJM 2013; 368: /20 patients demonstrated increased uptake on Iodine-124 PET Dosimetry performed on I-124 PET 8/20 patients reached threshold of 20Gy to iodine-avid lesions

8 SELIMETRY Dosimetry Pathway Baseline I-123 Scan Selumetinib Repeat I-123 Scan I-131 Therapy I-131 Dosimetry Scans rhtsh stimulation Confirm iodine refractory disease 75mg bd for 4 weeks rhtsh stimulation Check for iodine uptake If uptake is confirmed, proceed to dosimetry SPECT/CT at 5, 24, 48 and 72 hours Continue on selumetinib rhtsh stimulation 5.5GBq I-131 NaI SPECT/CT at 24, 48, 72 and 144 hours SELIMETRY trial includes exploratory objectives to investigate the role of lesion dosimetry using I-123 SPECT/CT to predict response to I-131 therapy 60 patients to be recruited over 4 years Eight sites in UK

9 SELIMETRY Acquisition Parameters Parameter I-123 I-131 Collimator Medium-energy general High-energy general purpose purpose (MEGP) (HEGP) Peak Energy window (20%) 159 kev ± 10% 364 kev ± 10% Low Scatter Energy window (6%) 138 kev ± 3% 318 kev ± 3% High Scatter Energy window (6%) 180 kev ± 3% 413 kev ± 3% Matrix 128 x 128 SPECT movement Body Contour (or radius as close to phantom as possible) Projections 72 (5 /projection) Time per projection 60 s* CT Standard low dose protocol Reconstruction OSEM, 40it, 4sub, no post-filtering, TEW + CTAC

10 SELIMETRY: Site set-up The core laboratory is the Royal Marsden Hospital, and RSCH acted as the pilot site for the Quantitative Imaging protocol development and testing. Characterisation of GE Optima 640 SPECT/CT system at RSCH: Partial Volume Deadtime

11 SELIMETRY: Calibration Factors Six fillable cylindrical inserts of increasing volume: 1x1cm = 0.8ml 2x2cm = 6.3ml 3x3cm = 21.0ml 4x4cm = 50.7ml 5x5cm = 98.0ml 6.3x6.3cm = 196.3ml Scan together inside NEMA IEC body phantom at 8cm radius Prepared with 100MBq I-123 NaI diluted in 400ml with 1g Potassium Iodide and 1g Sodium Thiosulphate Repeat with 100MBq I-131

12 SELIMETRY: RSCH Results 1 I-123 I-131 RC fit 1 / x Radioiodine 123 I I

13 SELIMETRY: Dead time characterisation Jaszczak cylinder phantom half-filled with water and with I-131 activity increasing from 20MBq to 2800MBq (added from two 4ml stock solutions of 100MBq/ml and 600MBq/ml) 100k counts acquired for each activity Test in normal and fast modes

14 SELIMETRY: RSCH Results 2 With fast mode enabled, dead time losses are observed for activities > 1.6GBq (37 kcps) and are <12% up to 2.8GBq (60kcps) Curves extrapolated from points up to 40MBq to estimate true counts, n. Paralysable model assumed: m = n exp(-nτ)

15 SELIMETRY: Quality Control Requirements Check Within preceding Limits Energy peak position month - Integral CFOV < 4% 123 I intrinsic (20 million count) uniformity month (allow time to Differential CFOV < 3% correct artefacts where 131 I intrinsic (20 million count) uniformity necessary) No significant uniformity artefacts 99m Tc intrinsic (20 million count) uniformity week COR for both the MEGP and HEGP collimators month SPECT/CT system alignment checks month Within local limits Extrinsic HEGP and MEGP floods week QC of radionuclide calibrator day

16 What we ve learned Multi-centre standardisation of quantitative imaging protocol is feasible Need to check high count-rate mode is set up properly by manufacturer before doing calibrations more on this later (Nick Bates) Artefacts in PVC curves may occur if sources are not adequately spaced; investigating significance Doses to staff doing dead time calibrations do not exceed occupational constraints but could be further reduced with use of mobile shielding

17 Conclusions Quantitative imaging & dosimetry sub-study of SELIMETRY using I-123 SPECT/CT as a surrogate for I-131 The trial will help to make dosimetry visible to clinicians The trial will generate valuable clinical trial evidence for dosimetry Along with standardisation of metrology protocols, this is the key to the successful implementation of dosimetry in MRT

18 Acknowledgements Rebecca Gregory, Glenn Flux Royal Marsden Hospital Jill Merrett, Andy Fenwick National Physical Laboratory Hannah Wiedner and the meeting organisers for the invitation to speak