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.
Our aim was to report the use of 64 Cu and 67 Cu as a theranostic pair of radionuclides in human subjects. An additional aim was to measure whole-organ dosimetry of 64 Cu and 67 Cu attached to the somatostatin analog octreotate using the sarcophagine MeCOSar chelator (SAR-TATE) in subjects with somatostatin receptor-expressing lesions confined to the cranium, thereby permitting normal-organ dosimetry for the remainder of the body. Methods: Pretreatment PET imaging studies were performed up to 24 h after injection of [ 64 Cu]Cu-SARTATE, and normal-organ dosimetry was estimated using OLINDA/EXM. Subsequently, the trial subjects with multifocal meningiomas were given therapeutic doses of [ 67 Cu]Cu-SARTATE and imaged over several days using SPECT/CT. Results: Five subjects were initially recruited and imaged using PET/CT before treatment. Three of the subjects were subsequently administered 4 cycles each of [ 67 Cu]Cu-SARTATE followed by multiple SPECT/CT imaging time points. No serious adverse events were observed, and no adverse events led to withdrawal from the study or discontinuation from treatment. The estimated mean effective dose was 3.95 3 10 22 mSv/MBq for [ 64 Cu]Cu-SARTATE and 7.62 3 10 22 mSv/MBq for [ 67 Cu]Cu-SARTATE. The highest estimated organ dose was in spleen, followed by kidneys, liver, adrenals, and small intestine. The matched pairing was shown by PET and SPECT intrasubject imaging to have nearly identical targeting to tumors for guiding therapy, demonstrating a potentially accurate and precise theranostic product. Conclusion: 64 Cu and 67 Cu show great promise as a theranostic pair of radionuclides. Further clinical studies will be required to examine the therapeutic dose required for [ 67 Cu]Cu-SARTATE for various indications. In addition, the ability to use predictive 64 Cu-based dosimetry for treatment planning with 67 Cu should be further explored.
Positron (β+) emitting radionuclides have been used for positron emission tomography (PET) imaging in diagnostic medicine since its development in the 1950s. Development of a fluorinated glucose analog, fluorodeoxyglucose, labelled with a β+ emitter fluorine-18 (18F-FDG), made it possible to image cellular targets with high glycolytic metabolism. These targets include cancer cells based on increased aerobic metabolism due to the Warburg effect, and thus, 18F-FDG is a staple in nuclear medicine clinics globally. However, due to its attention in the diagnostic setting, the therapeutic potential of β+ emitters have been overlooked in cancer medicine. Here we show the first in vitro evidence of β+ emitter cytotoxicity on prostate cancer cell line LNCaP C4-2B when treated with 20 Gy of 18F. Monte Carlo simulation revealed thermalized positrons (sub-keV) traversing DNA can be lethal due to highly localized energy deposition during the thermalization and annihilation processes. The computed single and double strand breakages were ~ 55% and 117% respectively, when compared to electrons at 400 eV. Our in vitro and in silico data imply an unexplored therapeutic potential for β+ emitters. These results may also have implications for emerging cancer theranostic strategies, where β+ emitting radionuclides could be utilized as a therapeutic as well as a diagnostic agent once the challenges in radiation safety and protection after patient administration of a radioactive compound are overcome.
AimsTo investigate and optimize the SPECTRE (Single Photon Emission Computed Theranostic REconstruction) reconstruction approach, using the hybrid kernelized expectation maximization (HKEM) algorithm implemented in the software for tomographic image reconstruction (STIR) software library, and to demonstrate the feasibility of performing algorithm exploration and optimization in 2D. Optimal SPECTRE parameters were investigated for the purpose of improving SPECT-based radionuclide therapy (RNT) dosimetry estimates.MethodsUsing the NEMA IEC body phantom as the test object, SPECT data were simulated to model an early and late imaging time point following a typical therapeutic dose of 8 GBq of 177Lu. A theranostic 68Ga PET-prior was simulated for the SPECTRE reconstructions. The HKEM algorithm parameter space was investigated for SPECT-unique and PET-SPECT mutual features to characterize optimal SPECTRE parameters for the simulated data. Mean and maximum bias, coefficient of variation (COV %), recovery, SNR and root-mean-square error (RMSE) were used to facilitate comparisons between SPECTRE reconstructions and OSEM reconstructions with resolution modelling (OSEM_RM). 2D reconstructions were compared to those performed in 3D in order to evaluate the utility of accelerated algorithm optimization in 2D. Segmentation accuracy was evaluated using a 42% fixed threshold (FT) on the 3D reconstructed data.ResultsSPECTRE parameters that demonstrated improved image quality and quantitative accuracy were determined through investigation of the HKEM algorithm parameter space. OSEM_RM and SPECTRE reconstructions performed in 2D & 3D were qualitatively and quantitatively similar, with SPECTRE showing an average reduction in background COV % by a factor of 2.7 and 3.3 for the 2D case and 3D case respectively. The 42% FT analysis produced an average % volume difference from ground truth of 158% and 26%, for the OSEM_RM and SPECTRE reconstructions, respectively.ConclusionsThe SPECTRE reconstruction approach demonstrates significant potential for improved SPECT image quality, leading to more accurate RNT dosimetry estimates when conventional segmentation methods are used. Exploration and optimization of SPECTRE benefited from both fast reconstruction times afforded by first considering the 2D case. This is the first in-depth exploration of the SPECTRE reconstruction approach, and as such, it reveals several insights for reconstructing SPECT data using PET side-information.
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