Title: Internal Dosimetry For Risk Estimates From Low Dose Non-Uniform Internal Exposure From Nuclear Medicine Procedures
Funder: Department of Health and Social Care

Abstract: Background: Validation of the linear-no-threshold extrapolation model is hampered by little data and large uncertainties on the low absorbed doses calculated from occupational exposures or from radiation incidents. Notably, over 625,000 diagnostic and therapeutic nuclear medicine oncological and non-oncological procedures are performed each year in England alone (NHS imaging and radiodiagnostic activity in England 2013/2014 release, NHS England). A large majority of these receive absorbed doses below 100 mSv which is in the critical range of uncertainty. Effective doses provided for Diagnostic Reference Levels do not allow for the wide variation in patient dosimetry, primarily due to initial wash out phases. Accurate dosimetry data for even a very small proportion of these patients, combined with patient follow up, would provide the information necessary to establish a robust model for low absorbed dose and absorbed dose rate effects. Significant advances in dosimetry methodology for radionuclide therapy over the last 5-10 years can now be applied to diagnostic studies to acquire these data. Aims: The overall aim will be to develop a simple and inexpensive methodology to determine accurately organ and effective doses for diagnostic nuclear medicine procedures. This will provide a solid basis for a future multicentre prospective study to establish the effect of low absorbed doses and absorbed dose rates from non-homogenous internal radiation on the incidence of secondary malignancies and on non-cancer effects. The planning of such a study would also be an aim of this project. Dosimetry for molecular radiotherapy has advanced significantly in the past decade although the techniques developed can be complex and are not easily applicable to routine diagnostic studies. This study will adapt these techniques to a limited patient cohort to determine the accuracy with which a more practical method of dosimetry may be performed. Research plan: Diagnostic studies using a range of radionuclides will be identified for evaluation. Whole body dosimetry will be performed using high sensitivity detectors, hand held Geiger counters and image data obtained from the studies. Organ and tumour dosimetry will be performed using techniques adapted from therapeutic studies. The uncertainties on the absorbed doses, as a function of the number of measurements and scans, will be calculated using a system of error analysis used for wholebody dosimetry of I-131 mIBG treatments of adult and paediatric neuroendocrine tumours and a recently developed, more sophisticated method based on error propagation for organ dosimetry. Verification of organ dosimetry and the associated uncertainties calculated will be performed using bespoke anthropomorphic phantoms produced with 3D printing technology. Research team: The radioisotope physics group at the RMH/ICR has extensive experience of quantitative imaging with SPECT/CT and PET/CT, and with internal dosimetry for molecular radiotherapy. The PI is a member of an ICRP working party to address dosimetry for radionuclide therapy, which will consider risk estimates from therapeutic procedures, and chair of the BNMS molecular radiotherapy committee radiotherapy committee which will provide national support for future studies. Members of the team are leading the development of uncertainty analysis for dosimetry, the culture and ethics of radiation protection, setting up multicentre imaging and dosimetry trials and other aspects of nuclear medicine imaging and therapy. Potential impact: This study will enable a future large scale trial to establish low dose effects and dose-rate response relationships from nuclear medicine procedures, which would allow quantification of radiation risks, taking into account non-homogeneous activity distributions. This could potentially lead to optimised activity administrations. A successful outcome from this study would lead to formation of a multicentre network to address the issues raised. In the longer term, the effect of low doses and low dose rates would be comprehensively addressed.

Lay abstract: The aim of this study is to develop simple methodology to determine accurately the radiation doses resulting from diagnostic nuclear medicine scanning. It is envisaged that this will lead to a subsequent large scale study to collect and record doses and long term effects that may be radiation induced. This will be particularly relevant for patients undergoing diagnostic nuclear medicine procedures, as cancer treatment improves and diagnosis is made earlier, although results from the study can be extrapolated to members of the public receiving radiation doses from occupational exposures or from nuclear incidents. There are little data concerning radiation induced cancers and non-cancer effects from exposure to low levels of radiation, particularly for internal sources distributed non-uniformly in the body. Current international radiation risk estimates are largely based on data obtained from nuclear incidents and from occupational exposures. Consequently there are large uncertainties on the doses estimated to be delivered to members of the public. In contrast, diagnostic nuclear medicine scans routinely deliver low level radiation doses in a controlled setting. There are over 625,000 such procedures each year in England. At present scanning is performed only to enable reporting of areas of abnormal uptake and the doses delivered to individual patients are not calculated. However scans of patients undergoing radionuclide therapy are often processed to provide absolute values of the internal distribution of radioactivity. From these values it is possible to calculate accurately the radiation doses delivered to each organ. In this study these methods for quantitative patient imaging, developed for therapy procedures, will be adapted for diagnostic studies. The radiation doses delivered to the patients will then be calculated. There will be an emphasis on calculating the uncertainties on these doses, as this will determine the number of patients needed for a subsequent larger study. The dosimetry will be validated using phantoms - physical models of patient anatomy produced with 3D printing technology - for which the results are known.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE;CANCER AND NEOPLASMS