Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical ...imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.
Clinical Use of PET/MR in Oncology: An Update Seifert, Robert; Kersting, David; Rischpler, Christoph ...
Seminars in nuclear medicine,
20/May , Volume:
52, Issue:
3
Journal Article
Peer reviewed
The combination of PET and MRI is one of the recent advances of hybrid imaging. Yet to date, the adoption rate of PET/MRI systems has been rather slow. This seems to be partially caused by the high ...costs of PET/MRI systems and the need to verify an incremental benefit over PET/CT or sequential PET/CT and MRI.
In analogy to PET/CT, the MRI part of PET/MRI was primarily used for anatomical imaging. Though this can be advantageous, for example in diseases where the superior soft tissue contrast of MRI is highly appreciated, the sole use of MRI for anatomical orientation lessens the potential of PET/MRI. Consequently, more recent studies focused on its multiparametric potential and employed diffusion weighted sequences and other functional imaging sequences in PET/MRI. This integration puts the focus on a more wholesome approach to PET/MR imaging, in terms of releasing its full potential for local primary staging based on multiparametric imaging and an included one-stop shop approach for whole-body staging. This approach as well as the implementation of computational analysis, in terms of radiomics analysis, has been shown valuable in several oncological diseases, as will be discussed in this review article.
The emerging use of immunotherapies in cancer treatment increases the risk of immunotherapy-related cardiotoxicity. In contrast to conventional chemotherapy, these novel therapies have expanded the ...forms and presentations of cardiovascular damage to a broad spectrum from asymptomatic changes to fulminant short- and long-term complications in terms of cardiomyopathy, arrythmia, and vascular disease. In cancer patients and, particularly, cancer patients undergoing (immune-)therapy, cardio-oncological monitoring is a complex interplay between pretherapeutic risk assessment, identification of impending cardiotoxicity, and post-therapeutic surveillance. For these purposes, the cardio-oncologist can revert to a broad spectrum of nuclear cardiological diagnostic workup. The most promising commonly used nuclear medicine imaging techniques in relation to immunotherapy will be discussed in this review article with a special focus on the continuous development of highly specific molecular markers and steadily improving methods of image generation. The review closes with an outlook on possible new developments of molecular imaging and advanced image evaluation techniques in this exciting and increasingly growing field of immunotherapy-related cardiotoxicity.
Abstract
The radioiodine isotope pair
124
I/
131
I is used in a theranostic approach for patient-specific treatment of differentiated thyroid cancer. Lesion detectability is notably higher for
124
I ...PET (positron emission tomography) than for
131
I gamma camera imaging but can be limited for small and low uptake lesions. The recently introduced silicon-photomultiplier-based (SiPM-based) PET/CT (computed tomography) systems outperform previous-generation systems in detector sensitivity, coincidence time resolution, and spatial resolution. Hence, SiPM-based PET/CT shows an improved detectability, particularly for small lesions. In this study, we compare the size-dependant minimum detectable
124
I activity (MDA) between the SiPM-based Biograph Vision and the previous-generation Biograph mCT PET/CT systems and we attempt to predict the response to
131
I radioiodine therapy of lesions additionally identified on the SiPM-based system. A tumour phantom mimicking challenging conditions (derived from published patient data) was used; i.e., 6 small spheres (diameter of 3.7–9.7 mm), 9 low activity concentrations (0.25–25 kBq/mL), and a very low signal-to-background ratio (20:1). List-mode emission data (single-bed position) were divided into frames of 4, 8, 16, and 30 min. Images were reconstructed with ordinary Poisson ordered-subsets expectation maximization (OSEM), additional time-of-flight (OSEM-TOF) or TOF and point spread function modelling (OSEM-TOF+PSF). The signal-to-noise ratio and the MDA were determined. Absorbed dose estimations were performed to assess possible treatment response to high-activity
131
I radioiodine therapy. The signal-to-noise ratio and the MDA were improved from the mCT to the Vision, from OSEM to OSEM-TOF and from OSEM-TOF to OSEM-TOF+PSF reconstructed images, and from shorter to longer emission times. The overall mean MDA ratio of the Vision to the mCT was 0.52 ± 0.18. The absorbed dose estimations indicate that lesions ≥ 6.5 mm with expected response to radioiodine therapy would be detectable on both systems at 4-min emission time. Additional smaller lesions of therapeutic relevance could be detected when using a SiPM-based PET system at clinically reasonable emission times. This study demonstrates that additional lesions with predicted response to
131
I radioiodine therapy can be detected. Further clinical evaluation is warranted to evaluate if negative
124
I PET scans on a SiPM-based system can be sufficient to preclude patients from blind radioiodine therapy.
Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation, with individual body composition influencing disease severity. Severe emphysema ...worsens symptoms through hyperinflation, which can be relieved by bronchoscopic lung volume reduction (BLVR). To investigate how body composition, assessed through CT scans, impacts outcomes in emphysema patients undergoing BLVR. Fully automated CT-based body composition analysis (BCA) was performed in patients with end-stage emphysema receiving BLVR with valves. Post-interventional muscle and adipose tissues were quantified, body size-adjusted, and compared to baseline parameters. Between January 2015 and December 2022, 300 patients with severe emphysema underwent endobronchial valve treatment. Significant improvements were seen in outcome parameters, which were defined as changes in pulmonary function, physical performance, and quality of life (QoL) post-treatment. Muscle volume remained stable (1.632 vs. 1.635 for muscle bone adjusted ratio (BAR) at baseline and after 6 months respectively), while bone adjusted adipose tissue volumes, especially total and pericardial adipose tissue, showed significant increase (2.86 vs. 3.00 and 0.16 vs. 0.17, respectively). Moderate to strong correlations between bone adjusted muscle volume and weaker correlations between adipose tissue volumes and outcome parameters (pulmonary function, QoL and physical performance) were observed. Particularly after 6-month, bone adjusted muscle volume changes positively corresponded to improved outcomes (ΔForced expiratory volume in 1 s FEV
, r = 0.440; ΔInspiratory vital capacity IVC, r = 0.397; Δ6Minute walking distance 6MWD, r = 0.509 and ΔCOPD assessment test CAT, r = -0.324; all p < 0.001). Group stratification by bone adjusted muscle volume changes revealed that groups with substantial muscle gain experienced a greater clinical benefit in pulmonary function improvements, QoL and physical performance (ΔFEV
%, 5.5 vs. 39.5; ΔIVC%, 4.3 vs. 28.4; Δ6MWDm, 14 vs. 110; ΔCATpts, -2 vs. -3.5 for groups with ΔMuscle, BAR% < -10 vs. > 10, respectively). BCA results among patients divided by the minimal clinically important difference for forced expiratory volume of the first second (FEV
) showed significant differences in bone-adjusted muscle and intramuscular adipose tissue (IMAT) volumes and their respective changes after 6 months (ΔMuscle, BAR% -5 vs. 3.4 and ΔIMAT, BAR% -0.62 vs. 0.60 for groups with ΔFEV1 ≤ 100 mL vs > 100 mL). Altered body composition, especially increased muscle volume, is associated with functional improvements in BLVR-treated patients.
Background New-generation silicon-photomultiplier (SiPM)-based PET/CT systems exhibit an improved lesion detectability and image quality due to a higher detector sensitivity. Consequently, the ...acquisition time can be reduced while maintaining diagnostic quality. The aim of this study was to determine the lowest .sup.18F-FDG PET acquisition time without loss of diagnostic information and to optimise image reconstruction parameters (image reconstruction algorithm, number of iterations, voxel size, Gaussian filter) by phantom imaging. Moreover, patient data are evaluated to confirm the phantom results. Methods Three phantoms were used: a soft-tissue tumour phantom, a bone-lung tumour phantom, and a resolution phantom. Phantom conditions (lesion sizes from 6.5 mm to 28.8 mm in diameter, lesion activity concentration of 15 kBq/mL, and signal-to-background ratio of 5:1) were derived from patient data. PET data were acquired on an SiPM-based Biograph Vision PET/CT system for 10 min in list-mode format and resampled into time frames from 30 to 300 s in 30-s increments to simulate different acquisition times. Different image reconstructions with varying iterations, voxel sizes, and Gaussian filters were probed. Contrast-to-noise-ratio (CNR), maximum, and peak signal were evaluated using the 10-min acquisition time image as reference. A threshold CNR value greater than or equal to 5 and a maximum (peak) deviation of + or - 20% were considered acceptable. 20 patient data sets were evaluated regarding lesion quantification as well as agreement and correlation between reduced and full acquisition time standard uptake values (assessed by Pearson correlation coefficient, intraclass correlation coefficient, Bland-Altman analyses, and Krippendorff's alpha). Results An acquisition time of 60 s per bed position yielded acceptable detectability and quantification results for clinically relevant phantom lesions greater than or equal to 9.7 mm in diameter using OSEM-TOF or OSEM-TOF+PSF image reconstruction, a 4-mm Gaussian filter, and a 1.65 x 1.65 x 2.00-mm.sup.3 or 3.30 x 3.30 x 3.00-mm.sup.3 voxel size. Correlation and agreement of patient lesion quantification between full and reduced acquisition times were excellent. Conclusion A threefold reduction in acquisition time is possible. Patients might benefit from more comfortable examinations or reduced radiation exposure, if instead of the acquisition time the applied activity is reduced. Keywords: Positron emission tomography, FDG, Acquisition time, Silicon-based photomultiplier, Digital PET, Protocol optimisation, Lymphoma
Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual Perugini score. We aimed to ...implement a quantification method of cardiac amyloid deposits in patients with suspected cardiac amyloidosis and to compare performance to visual scoring.
136 patients received 99mTc-DPD-bone scintigraphy including SPECT/CT of the thorax in case of suspicion of cardiac amyloidosis. Imaging phantom studies were performed to determine the scaling factor for standardized uptake value (SUV) quantification from SPECT/CT. Myocardial tracer uptake was quantified in a whole heart volume of interest.
Forty-five patients were diagnosed with CA. A strong relationship between cardiac SUVmax and Perugini score was found (Spearman r 0.75, p < 0.0001). Additionally, tracer uptake in bone decreased with increasing cardiac SUVmax and Perugini score (p < 0.0001). ROC analysis revealed good performance of the SUVmax for the detection of ATTR-CA with AUC of 0.96 ± 0.02 (p < 0.0001) with sensitivity 98.7% and specificity 87.2%.
We demonstrate an accessible and accurate quantitative SPECT approach in CA. Quantitative assessment of the cardiac tracer uptake may improve diagnostic accuracy and risk classification. This method may enable monitoring and assessment of therapy response in patients with ATTR amyloidosis.
During its development the malaria parasite P. falciparum has to adapt to various different environmental contexts. Key cellular mechanisms involving G-protein coupled signal transduction chains are ...assumed to act at these interfaces. Heterotrimeric G-proteins are absent in Plasmodium. We here describe the first cloning and expression of a putative, non-canonical Ras-like G protein (acronym PfG) from Plasmodium. PfG reveals an open reading frame of 2736 bp encoding a protein of 912 amino acids with a theoretical pI of 8.68 and a molecular weight of 108.57 kDa. Transcript levels and expression are significantly increased in the erythrocytic phase in particular during schizont and gametocyte formation. Most notably, PfG has GTP binding capacity and GTPase activity due to an EngA2 domain present in small Ras-like GTPases in a variety of Bacillus species and Mycobacteria. By contrast, plasmodial PfG is divergent from any human alpha-subunit. PfG was expressed in E. coli as a histidine-tagged fusion protein and was stable only for 3.5 hours. Purification was only possible under native conditions by Nickel-chelate chromatography and subsequent separation by Blue Native PAGE. Binding of a fluorescent GTP analogue BODIPY® FL guanosine 5'O-(thiotriphosphate) was determined by fluorescence emission. Mastoparan stimulated GTP binding in the presence of Mg2+. GTPase activity was determined colorimetrically. Activity expressed as absolute fluorescence was 50% higher for the human paralogue than the activity of the parasitic enzyme. The PfG protein is expressed in the erythrocytic stages and binds GTP after immunoprecipitation. Immunofluorescence using specific antiserum suggests that PfG localizes to the parasite cytosol. The current data suggest that the putitative, Ras-like G-protein might be involved in a non-canonical signaling pathway in Plasmodium. Research on the function of PfG with respect to pathogenesis and antimalarial chemotherapy is currently under way.
Background The superior accuracy and sensitivity of .sup.18F-FDG-PET/CT in comparison to morphological imaging alone leads to an upstaging in up to 30% of lymphoma patients. Novel digital PET/CT ...scanners might enable to reduce administered tracer activity or scan time duration while maintaining diagnostic performance; this might allow for a higher patient throughput or a reduced radiation exposure, respectively. In particular, the radiation exposure reduction is of interest due to the often young age and high remission rate of lymphoma patients. Methods Twenty patients with (suspected) lymphoma (6 for initial staging, 12 after systemic treatment, 2 in suspicion of recurrence) sequentially underwent .sup.18F-FDG-PET/CT examinations on a digital PET/CT (Siemens Biograph Vision) with a total scan time duration of 15 min (reference acquisition protocol) and 5 min (reduced acquisition protocol) using continuous-bed-motion. Both data sets were reconstructed using either standalone time of flight (TOF) or in combination with point spread function (PSF), each with 2 and 4 iterations. Lesion detectability by blinded assessment (separately for supra- and infradiaphragmal nodal lesions and for extranodal lesions), lesion image quantification, and image noise were used as metrics to assess diagnostic performance. Additionally, Deauville Score was compared for all patients after systemic treatment. Results All defined regions were correctly classified in the images acquired with reduced emission time, and therefore, no changes in staging were observed. Lesion quantification was acceptable, that is, mean absolute percentage deviation of maximum and peak standardized uptake values were 6.8 and 6.4% (derived from 30 lesions). A threefold reduction of scan time duration led to an increase in image noise from 7.1 to 11.0% (images reconstructed with 4 iterations) and from 4.7 to 7.2% (images reconstructed with 2 iterations). No deviations in Deauville Score were observed. Conclusion These results suggest that scan time duration or administered tracer activity can be reduced threefold without compromising diagnostic performance. Especially a reduction of administered activity might allow for a lower radiation exposure and better health economics. Larger trials are warranted to confirm our results. Keywords: PET/CT, FDG, Image quality, Silicon photomultiplier, Lymphoma
PDF
