Theranostic SPECT reconstruction for improved resolution: application to radionuclide therapy dosimetry.

BACKGROUND: SPECT-derived dose estimates in tissues of diameter less than 3× system resolution are subject to significant losses due to the limited spatial resolution of the gamma camera. Incorporating resolution modelling (RM) into the SPECT reconstruction has been proposed as a possible solution; however, the images produced are prone to noise amplification and Gibbs artefacts. We propose a novel approach to SPECT reconstruction in a theranostic setting, which we term SPECTRE (single photon emission computed theranostic reconstruction); using a diagnostic PET image, with its superior resolution, to guide the SPECT reconstruction of the therapeutic equivalent. This report demonstrates a proof in principle of this approach. METHODS: We have employed the hybrid kernelised expectation maximisation (HKEM) algorithm implemented in STIR, with the aim of producing SPECT images with PET-equivalent resolution. We demonstrate its application in both a dual 68Ga/177Lu IEC phantom study and a clinical example using 64Cu/67Cu. RESULTS: SPECTRE is shown to produce images comparable in accuracy and recovery to PET with minimal introduction of artefacts and amplification of noise. CONCLUSION: The SPECTRE approach to image reconstruction shows improved quantitative accuracy with a reduction in noise amplification. SPECTRE shows great promise as a method of improving SPECT radioactivity concentrations, directly leading to more accurate dosimetry estimates in small structures and target lesions. Further investigation and optimisation of the algorithm parameters is needed before this reconstruction method can be utilised in a clinical setting.

Clustering effects in nanoparticle-enhanced ß- emitting internal radionuclide therapy: a Monte Carlo study.

We investigate the effects of an increase in the production of secondary electrons when a ß - source commonly used in internal radionuclide therapy, 67Cu, is radiolabelled to a super-paramagnetic iron oxide nanoparticle (SPION), with specific emphasis on the role of SPION cluster size and geometry. A positive relationship is found between the degree to which the nanoparticles are clustered and the associated radio-enhancement effects, with cluster population size playing a major role, as well as SPION separation within a cluster and the distance between clusters. Our simulation results indicate that SPIONs labelled with 67Cu can induce a nonlinear amplification in the number of secondary electrons produced of up to 4% in bulk, with localised regions of nearer inter-SPION separation producing an increase of over 400% for a 20 nm average SPION separation. Such variation in enhancement due to local concentration effects may help identify clinical strategies that enhance efficacy for a given radiation dosage, or achieve equal efficacy with reduced radiation dosage.

Impact of fluorescence emission from gold atoms on surrounding biological tissue-implications for nanoparticle radio-enhancement.

The addition of gold nanoparticles within target tissue (i.e. a tumour) to enhance the delivered radiation dose is a well studied radiotherapy treatment strategy, despite not yet having been translated into standard clinical practice. While several studies have used Monte Carlo simulations to investigate radiation dose enhancement by Auger electrons emitted from irradiated gold nanoparticles, none have yet considered the effects due to escaping fluorescence photons. Geant4 was used to simulate a water phantom containing 10 mg ml-1 uniformly dispersed gold (1% by mass) at 5 cm depth. Incident monoenergetic photons with energies either side of the gold K-edge at 73 keV and 139.5 keV were chosen to give the same attenuation contrast against water, where water is used as a surrogate for biological tissue. For 73 keV incident photons, adding 1% gold into the water phantom enhances the energy deposited in the phantom by a factor of ≈1.9 while 139.5 keV incident photons give a lower enhancement ratio of ≈1.5. This difference in enhancement ratio, despite the equivalent attenuation ratios, can be attributed to energy carried from the target into the surrounding volume by fluorescence photons for the higher incident photon energy. The energy de-localisation is maximal just above the K-edge with 36% of the initial energy deposit in the phantom lost to escaping fluorescence photons. Conversely we find that the absorption of more photons by gold in the phantom reduces the number of scattered photons and hence energy deposited in the surrounding volume by up to 6% for incident photons below the K-edge. For incident photons above the K-edge this is somewhat offset by fluorescence. Our results give new insight into the previously unstudied centimetre scale energy deposition outside a target, which will be valuable for the future development of treatment plans using gold nanoparticles. From these results, we can conclude that gold nanoparticles delivered to a target tumour are capable of increasing dose to the tumour whilst simultaneously decreasing scatter dose to surrounding healthy tissue.

Stochastic simulation of radium-223 dichloride therapy at the sub-cellular level.

Radium-223 dichloride ((223)Ra) is an alpha particle emitter and a natural bone-seeking radionuclide that is currently used for treating osteoblastic bone metastases associated with prostate cancer. The stochastic nature of alpha emission, hits and energy deposition poses some challenges for estimating radiation damage. In this paper we investigate the distribution of hits to cells by multiple alpha particles corresponding to a typical clinically delivered dose using a Monte Carlo model to simulate the stochastic effects. The number of hits and dose deposition were recorded in the cytoplasm and nucleus of each cell. Alpha particle tracks were also visualized. We found that the stochastic variation in dose deposited in cell nuclei ([Formula: see text]40%) can be attributed in part to the variation in LET with pathlength. We also found that [Formula: see text]18% of cell nuclei receive less than one sigma below the average dose per cell ([Formula: see text]15.4 Gy). One possible implication of this is that the efficacy of cell kill in alpha particle therapy need not rely solely on ionization clustering on DNA but possibly also on indirect DNA damage through the production of free radicals and ensuing intracellular signaling.