Hybrid adiabatic quantum computing for tomographic image reconstruction -- opportunities and limitations

Our goal is to reconstruct tomographic images with few measurements and a low signal-to-noise ratio. In clinical imaging, this helps to improve patient comfort and reduce radiation exposure. As quantum computing advances, we propose to use an adiabatic quantum computer and associated hybrid methods to solve the reconstruction problem. Tomographic reconstruction is an ill-posed inverse problem. We test our reconstruction technique for image size, noise content, and underdetermination of the measured projection data. We then present the reconstructed binary and integer-valued images of up to 32 by 32 pixels. The demonstrated method competes with traditional reconstruction algorithms and is superior in terms of robustness to noise and reconstructions from few projections. We postulate that hybrid quantum computing will soon reach maturity for real applications in tomographic reconstruction. Finally, we point out the current limitations regarding the problem size and interpretability of the algorithm

Accuracy comparison of various quantitative [99mTc]Tc-DPD SPECT/CT reconstruction techniques in patients with symptomatic hip and knee joint prostheses

Abstract Background There is a need for better diagnostic tools that identify loose total hip and knee arthroplasties. Here, we present the accuracy of different 99mTc-dicarboxypropandiphosphate ([99mTc]Tc-DPD) SPECT/CT quantification tools for the detection of loose prostheses in patients with painful hip and knee arthroplasties. Methods Quantitative reconstruction of mineral phase SPECT data was performed using Siemens xSPECT-Quant and xSPECT-Bone, with and without metal artefact reduction (iMAR) of CT-data. Quantitative data (SUVmax values) were compared to intraoperative diagnosis or clinical outcome after at least 1 year as standard of comparison. Cut-off values and accuracies were calculated using receiver operator characteristics. Accuracy of uptake quantification was compared to the accuracy of visual SPECT/CT readings, blinded for the quantitative data and clinical outcome. Results In this prospective study, 30 consecutive patients with 33 symptomatic hip and knee prostheses underwent [99mTc]Tc-DPD SPECT/CT. Ten arthroplasties were diagnosed loose and 23 stable. Mean-SUVmax was significantly higher around loose prostheses compared to stable prostheses, regardless of the quantification method (P = 0.0025–0.0001). Quantification with xSPECT-Bone-iMAR showed the highest accuracy (93.9% [95% CI 79.6–100%]) which was significantly higher compared to xSPECT-Quant-iMAR (81.8% [67.5–96.1%], P = 0.04) and xSPECT-Quant without iMAR (77.4% [62.4–92.4%], P = 0.02). Accuracies of clinical reading were non-significantly lower compared to quantitative measures (84.8% [70.6–99.1%] (senior) and 81.5% [67.5–96.1%] (trainee)). Conclusion Quantification with [99mTc]Tc-DPD xSPECT-Bone-iMAR discriminates best between loose and stable prostheses of all evaluated methods. The overall high accuracy of different quantitative measures underlines the potential of [99mTc]Tc-DPD-quantification as a biomarker and demands further prospective evaluation in a larger number of prosthesis

In-vivo inhibition of neutral endopeptidase 1 results in higher absorbed tumor doses of [177Lu]Lu-PP-F11N in humans: the lumed phase 0b study.

BACKGROUND A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation. Nevertheless, relatively low tumor radiation doses in patients indicate limited stability in humans. We aimed at evaluating the effect of sacubitril, an inhibitor of the neutral endopeptidase 1, on the stability and absorbed doses to tumors and organs by the cholecystokinin-2 receptor agonist [177Lu]Lu-PP-F11N in patients. In this prospective phase 0 study eight consecutive patients with advanced medullary thyroid carcinoma and a current somatostatin receptor subtype 2 PET/CT scan were included. Patients received two short infusions of ~ 1 GBq [177Lu]Lu-PP-F11N in an interval of ~ 4 weeks with and without Entresto® pretreatment in an open-label, randomized cross-over order. Entresto® was given at a single oral dose, containing 48.6 mg sacubitril. Adverse events were graded and quantitative SPECT/CT and blood sampling were performed. Absorbed doses to tumors and relevant organs were calculated. RESULTS Pretreatment with Entresto® showed no additional toxicity and increased the stability of [177Lu]Lu-PP-FF11N in blood significantly (p < 0.001). Median tumor-absorbed doses were 2.6-fold higher after Entresto® pretreatment (0.74 vs. 0.28 Gy/GBq, P = 0.03). At the same time, an increase of absorbed doses to stomach, kidneys and bone marrow was observed, resulting in a tumor-to-organ absorbed dose ratio not significantly different with and without Entresto®. CONCLUSIONS Premedication with Entresto® results in a relevant stabilization of [177Lu]Lu-PP-FF11N and consecutively increases radiation doses in tumors and organs. Trial registration clinicaltrails.gov, NCT03647657. Registered 20 August 2018

Cholecystokinin-2 Receptor Agonist 177Lu-PP-F11N for Radionuclide Therapy of Medullary Thyroid Carcinoma - Results of the Lumed Phase 0a Study.

Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades it is known that cholecystokinine-2 receptor (CCK2R) is a promising target for the treatment of MTC with radiolabeled minigastrin analogues. Unfortunately, kidney toxicity precluded their therapeutic application so far. In 6 consecutive patients we evaluated with advanced 3D dosimetry whether improved minigastrin analogue 177Lu-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH2 (177Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received two injections of about 1 GBq (~80 µg) 177Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random cross-over sequence in order to evaluate biodistribution, pharmacokinetics as well as tumor- and organ dosimetry. ECG, blood count and blood chemistry were measured up to 12 weeks after administration of 177Lu-PP-F11N to assess safety. Results: In all patients 177Lu-PP-F11N accumulation was visible in tumor tissue, stomach and kidneys. Altogether 13 tumors were eligible for dosimetry. The median (interquartile range = IQR) absorbed dose for tumors, stomach, kidneys and bone marrow was 0.88 Gy/GBq (0.85-1.04), 0.42 (0.25-1.01), 0.11 (0.07-0.13) and 0.028 (0.026-0.034). These resulted in a median (IQR) tumor-to-kidney dose ratio of 11.6 (8.11-14.4) without SG and 13.0 (10.2-18.6) with SG, which were not significantly different (P = 1.0). The median (IQR) tumor-to-stomach dose ratio was 3.34 (1.14-4.7). Adverse reactions (mainly hypotension, flushing and hypokalemia) were self-limiting and not higher than grade 1. Conclusion:177Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With little kidney and bone marrow radiation dose 177Lu-PP-F11N shows promising biodistribution. The dose limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of 177Lu-PP-F11N

An Insight into the Sialotranscriptome of Simulium nigrimanum, a Black Fly Associated with Fogo Selvagem in South America

Pemphigus foliaceus is a life threatening skin disease that is associated with autoimmunity to desmoglein, a skin protein involved in the adhesion of keratinocytes. This disease is endemic in certain areas of South America, suggesting the mediation of environmental factors triggering autoimmunity. Among the possible environmental factors, exposure to bites of black flies, in particular Simulium nigrimanum has been suggested. In this work, we describe the sialotranscriptome of adult female S. nigrimanum flies. It reveals the complexity of the salivary potion of this insect, comprised by over 70 distinct genes within over 30 protein families, including several novel families, even when compared with the previously described sialotranscriptome of the autogenous black fly, S. vittatum. The uncovering of this sialotranscriptome provides a platform for testing pemphigus patient sera against recombinant salivary proteins from S. nigrimanum and for the discovery of novel pharmacologically active compounds