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Molecular radiotherapy is a rapidly developing field with new vector and isotope combinations continually added to market. As with any radiotherapy treatment, it is vital that the absorbed dose and toxicity profile are adequately characterised. Methodologies for absorbed dose calculations for radiopharmaceuticals were generally developed to characterise stochastic effects and not suited to calculations on a patient-specific basis. There has been substantial scientific and technological development within the field of molecular radiotherapy dosimetry to answer this challenge. The development of imaging systems and advanced processing techniques enable the acquisition of accurate measurements of radioactivity within the body. Activity assessment combined with dosimetric models and radiation transport algorithms make individualised absorbed dose calculations not only feasible, but commonplace in a variety of commercially available software packages. The development of dosimetric parameters beyond the absorbed dose has also allowed the possibility to characterise the effect of irradiation by including biological parameters that account for radiation absorbed dose rates, gradients and spatial and temporal energy distribution heterogeneities. Molecular radiotherapy is in an exciting time of its development and the application of dosimetry in this field can only have a positive influence on its continued progression., (Copyright © 2020. Published by Elsevier Ltd.)

This study evaluates the dosimetric performance of the polymer gel dosimeter 'Methacrylic and Ascorbic acid in Gelatin, initiated by Copper' and its suitability for quality assurance and analysis of I-131-targeted radionuclide therapy dosimetry. Four batches of gel were manufactured in-house and sets of calibration vials and phantoms were created containing different concentrations of I-131-doped gel. Multiple dose measurements were made up to 700 h post preparation and compared to equivalent Monte Carlo simulations. In addition to uniformly filled phantoms the cross-dose distribution from a hot insert to a surrounding phantom was measured. In this example comparisons were made with both Monte Carlo and a clinical scintigraphic dosimetry method. Dose-response curves generated from the calibration data followed a sigmoid function. The gels appeared to be stable over many weeks of internal irradiation with a delay in gel response observed at 29 h post preparation. This was attributed to chemical inhibitors and slow reaction rates of long-chain radical species. For this reason, phantom measurements were only made after 190 h of irradiation. For uniformly filled phantoms of I-131 the accuracy of dose measurements agreed to within 10% when compared to Monte Carlo simulations. A radial cross-dose distribution measured using the gel dosimeter compared well to that calculated with Monte Carlo. Small inhomogeneities were observed in the dosimeter attributed to non-uniform mixing of monomer during preparation. However, they were not detrimental to this study where the quantitative accuracy and spatial resolution of polymer gel dosimetry were far superior to that calculated using scintigraphy. The difference between Monte Carlo and gel measurements was of the order of a few cGy, whilst with the scintigraphic method differences of up to 8 Gy were observed. A manipulation technique is also presented which allows 3D scintigraphic dosimetry measurements to be compared to polymer gel dosimetry measurements without generating misleading errors due to the limited spatial resolution.

There is a lack of standardized methodology to perform dose calculations for targeted radionuclide therapy and at present no method exists to objectively evaluate the various approaches employed. The aim of the work described here was to investigate the practicality and accuracy of calibrating polymer gel dosimeters such that dose measurements resulting from complex activity distributions can be verified. Twelve vials of the polymer gel dosimeter, 'MAGIC', were uniformly mixed with varying concentrations of P-32 such that absorbed doses ranged from 0 to 30 Gy after a period of 360 h before being imaged on a magnetic resonance scanner. In addition, nine vials were prepared and irradiated using an external 6 MV x-ray beam. Magnetic resonance transverse relaxation time, T2, maps were obtained using a multi-echo spin echo sequence and converted to R2 maps (where T2 = 1/R2). Absorbed doses for P-32 irradiated gel were calculated according to the medical internal radiation dose schema using EGSnrc Monte Carlo simulations. Here the energy deposited in cylinders representing the irradiated vials was scored. A relationship between dose and R(2) was determined. Effects from oxygen contamination were present in the internally irradiated vials. An increase in O2 sensitivity over those gels irradiated externally was thought to be a result of the longer irradiation period. However, below the region of contamination dose response appeared homogenous. Due do a drop-off of dose at the periphery of the internally irradiated vials, magnetic resonance ringing artefacts were observed. The ringing did not greatly affect the accuracy of calibration, which was comparable for both methods. The largest errors in calculated dose originated from the initial activity measurements, and were approximately 10%. Measured R2 values ranged from 5-35 s(-1) with an average standard deviation of 1%. A clear relationship between R2 and dose was observed, with up to 40% increased sensitivity for internally irradiated gels. Curve fits to the calibration data followed a single exponential function. The correlation coefficients for internally and externally irradiated gels were 0.991 and 0.985, respectively. With the ability to accurately calibrate internally dosed polymer gels, this technology shows promise as a means to evaluate dosimetry methods, particularly in cases of non-uniform uptake of a radionuclide.