Purpose To investigate and compare the quantitative accuracy of ⁹⁰Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. Methods A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of ⁹⁰Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Results Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter 20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Conclusion Current generation ToF scanners can consistently reconstruct ⁹⁰Y activity concentrations, but they underestimate activity concentrations in small structures (≤37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer.

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative ‘hot spot’ imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice.

This study aims to assess both feasibility and accuracy of renal dosimetry imaging protocols in patients receiving Lutate therapy for neuroendocrine tumours (NETs), when data acquisition over multiple days is not possible on all cycles. Patients who had received a full 4 cycles of Lutate therapy with complete imaging at each cycle were included. Imaging consisted of quantitative SPECT/CT of the kidneys at 4, 24 and 96–120 h post injection. Renal absorbed dose was calculated for each data set, and in addition, five alternative methods were explored for comparison. Method 1: a patient average clearance time (t1/2 average) derived from the first half of contributing patient data was used to estimate absorbed dose for subsequent patients based on 4 h imaging alone; method 2: t1/2 average was applied to subsequent patients on 24 h imaging alone; method 3: a patient-specific clearance rate (t1/2 patient) was determined from complete image data of cycle 1 and applied subsequently to remaining cycles using 4 h image data alone; method 4: t1/2 patient was applied to 24 h imaging alone in subsequent cycles; method 5: the 120 h data was estimated on subsequent cycles based on the cycle 1 fraction of injected activity (%IA) at 24 and 120 h. Twenty treatments from 18 patients, resulting in 80 cycles of therapy, were analysed. The measured average renal absorbed dose per cycle of treatment was 0.38 ± 0.19 Gy/GBq when derived from full imaging data. The use of t1/2 average applied to a single time point led to large deviations of dose estimates from true values (on average 59% and 30%, when using 4 h data and 24 h data, respectively). The use of complete image data on cycle 1 and the derivation of t1/2 patient led to improved dose estimates, with an average deviation from true values of 13% and 2% when using 4 h data only and 24 h data only, respectively. The use of a 120 h %IA derived from cycle 1 led to an average deviation from true dose estimates of 14%. In instances where demands on both patients and facilities make multiple time point data acquisition impractical, renal dosimetry is best derived through complete imaging at cycle 1 only followed by a single 24 h imaging time point on subsequent cycles, assuming no significant changes in renal function during the time course of therapy.

The aim of this study was to investigate the relationship between absorbed dose and response of colorectal cancer liver metastases treated with [90Y]-resin microspheres and to explore possible clinical and imaging derived prognostic factors. FDG PET/CT was used to measure response of individual lesions to a measured absorbed dose, derived from post-treatment 90Y PET imaging. Predicted dose was also derived from planning [99mTc]-MAA SPECT data. Peak standardised uptake value and total lesion glycolysis (TLG) were explored as response measures, and compared to dose metrics including average dose (D avg), biologically effective dose, minimum dose to 70% of lesion volume and volume receiving at least 50 Gy. Prognostic factors examined included baseline TLG, RAS mutation status, FDG heterogeneity and dose heterogeneity. In an exploratory analysis, response and clinico-pathological variables were evaluated and compared to overall survival. Sixty-three lesions were analysed from 22 patients. Poor agreement was seen between predicted and measured dose values. TLG was a superior measure of response, and all dose metrics were significant prognostic factors, with a D avg of ~50 Gy derived as the critical threshold for a significant response (>50% reduction in TLG). No significant correlation was found between baseline TLG or RAS mutation status and response. Measured dose heterogeneity was a significant prognostic factor and when combined with D avg had a positive predictive value for response >80%. In the exploratory analysis for prognostic factors of survival, low hepatic tumour burden and mean reduction in TLG >65% were independently associated with improved overall survival. Lesions receiving an average dose greater than 50 Gy are likely to have a significant response. For lesions receiving less than 50 Gy, dose heterogeneity is a significant prognostic factor. Lesions receiving an average dose less than 20 Gy are unlikely to respond. A reduction in TLG may be associated with improved overall survival.

Aim: To report the use of copper-64 and copper-67 as a theranostic pair of radionuclides in human subjects. In addition, to measure whole organ dosimetry of copper-64 and copper-67 attached to the somatostatin analogue Octreotate using the sarcophagine MeCOSAR chelator (“SARTATE”) in subjects with somatostatin receptor-expressing lesions confined to the cranium, thereby permitting normal organ dosimetry for the remainder of the body. Methods: Pre-treatment PET imaging studies were performed up to 24 hours after injection of [⁶⁴Cu]Cu-SARTATE and normal organ dosimetry estimates were made using OLINDA/EXM. Subsequently the trial subjects with multifocal meningiomas were given therapeutic doses of [⁶⁷Cu]Cu-SARTATE and imaged over a number of days using SPECT/CT. Results: Five subjects were initially recruited and imaged using PET/CT prior to treatment. Three of the subjects were subsequently administered four cycles each of [⁶⁷Cu]Cu-SARTATE followed by multiple SPECT/CT imaging timepoints. No serious adverse events (SAEs) were observed and no adverse events led to withdrawal from the study or discontinuation from treatment. The mean Effective Dose estimated was 3.95 × 10^-2 mSv/MBq for [⁶⁴Cu]Cu-SARTATE and 7.62 × 10^-2 mSv/MBq for [⁶⁷Cu]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 intra-subject imaging to have near identical targeting to tumours for guiding therapy, demonstrating a potentially accurate and precise theranostic product. Conclusion: Copper-64 and copper-67 show great promise as a theranostic pair of radionuclides. Further clinical studies will be required to examine the therapeutic dose required for [⁶⁷Cu]Cu-SARTATE for various indications. In addition, the ability to use predictive copper-64 based dosimetry for treatment planning with copper-67 should be further explored.

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.