Primary Data on ATTR-Amyloidosis Prevalence Among Elderly Patients With Left Ventricular Hypertrophy in Russia.

AIM: To estimate the prevalence of amyloid cardiomyopathy (CM) caused by transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) amyloidosis among patients aged >65 years with interventricular septal (IVS) hypertrophy of ≥14 mm. MATERIAL AND METHODS: From January through August 2023, 60 patients (mean age 7.2±7.3 years, 34 (56.67%) men) were enrolled. Patients meeting the inclusion criteria underwent an echocardiographic study with determining the myocardial longitudinal strain, myocardial scintigraphy with 99mTc-pyrfotech, myocardial single-photon emission computed tomography, measurement of N-terminal fragment of brain natriuretic peptide and troponin I, and the immunochemical study of serum and urine proteins with measurement of free light chains. In the presence of grades 2 and 3 radiopharmaceutical uptake according to scintigraphy, a molecular genetic study was performed for differential diagnosis of wild-type transthyretin amyloidosis (wtATTR) and hereditary/variant (hATTR) ATTR-CM. RESULTS: According to data of myocardial scintigraphy with 99mTc-pyrfotech, grade 3 uptake in the absence of monoclonal secretion was detected in 5 (8.3%) cases and grade 2 radiotracer uptake in the absence of monoclonal secretion was detected in 6 (10%) patients. Myeloma complicated by AL amyloidosis and primary AL amyloidosis were found in 5 (8.3%) patients. CONCLUSION: Among patients aged ≥65 years with IVS hypertrophy ≥14 mm, amyloid CM was detected in 20% of cases (12 patients), including 5 cases (8.3%) of AL amyloidosis and 7 cases (11.7%) of ATTR amyloidosis.

Surface ligand-regulated renal clearance of MRI/SPECT dual-modality nanoprobes for tumor imaging.

BACKGROUND: The general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape. RESULTS: In this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments. CONCLUSIONS: We believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.

In Vivo Mapping of Myocardial Injury Outside the Infarct Zone: Tissue at an Intermediate Pathological State.

BACKGROUND: The goal was to determine the feasibility of mapping the injured-but-not-infarcted myocardium using 99mTc-duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted. METHODS AND RESULTS: Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30-minute ligation. In vivo single-photon emission computed tomography was acquired after 3 hours (n=6) using 99mTc-duramycin, a phosphatidylethanolamine-specific radiopharmaceutical. The 99mTc-duramycin+ areas were compared with infarct and area-at-risk (n=8). Cardiomyocytes and endothelial cells were isolated for gene expression profiling. Cardiac function was measured with echocardiography (n=6) at 4 weeks. In vivo imaging with 99mTc-duramycin identified the infarct (3.9±2.4% of the left ventricle and an extensive area 23.7±2.2% of the left ventricle) with diffuse signal outside the infarct, which is pathologically between normal and infarcted (apoptosis 1.8±1.6, 8.9±4.2, 13.6±3.8%; VCAM-1 [vascular cell adhesion molecule 1] 3.2±0.8, 9.8±4.1, 15.9±4.2/mm2; tyrosine hydroxylase 14.9±2.8, 8.6±4.4, 5.6±2.2/mm2), with heterogeneous changes including scattered micronecrosis, wavy myofibrils, hydropic change, and glycogen accumulation. The 99mTc-duramycin+ tissue is quantitatively smaller than the area-at-risk (26.7% versus 34.4% of the left ventricle, P=0.008). Compared with infarct, gene expression in the 99mTc-duramycin+-noninfarct tissue indicated a greater prosurvival ratio (BCL2/BAX [B-cell lymphoma 2/BCL2-associated X] 7.8 versus 5.7 [cardiomyocytes], 3.7 versus 3.2 [endothelial]), and an upregulation of ion channels in electrophysiology. There was decreased contractility at 4 weeks (regional fractional shortening -8.6%, P<0.05; circumferential strain -52.9%, P<0.05). CONCLUSIONS: The injured-but-not-infarcted tissue, being an intermediate zone between normal and infarct, is mapped in vivo using phosphatidylethanolamine-based imaging. The intermediate zone contributes significantly to cardiac dysfunction.

Controllable synthesis of barium carbonate nano- and microparticles for SPECT and CT imaging.

The design and synthesis of nano- and microcarriers for preclinical and clinical imaging are highly attractive due to their unique features, for example, multimodal properties. However, broad translation of these carriers into clinical practice is postponed due to the unknown biological reactivity of the new components used for their synthesis. Here, we have developed microcarriers (∼2-3 µm) and  nanocarriers (<200 nm) made of barium carbonate (BaCO3) for multiple imaging applications in vivo. In general, barium in the developed carriers can be used for X-ray computed tomography, and the introduction of a diagnostic isotope (99mTc) into the BaCO3 structure enables in vivo visualization using single-photon emission computed tomography. The bioimaging has shown that the radiolabeled BaCO3 nano- and microcarriers had different biodistribution profiles and tumor accumulation efficiencies after intratumoral and intravenous injections. In particular, in the case of intratumoral injection, all the types of used carriers mostly remained in the tumors (>97%). For intravenous injection, BaCO3 microcarriers were mainly localized in the lung tissues. However, BaCO3 NPs were mainly accumulated in the liver. These results were supported by ex vivo fluorescence imaging, direct radiometry, and histological analysis. The BaCO3-based micro- and nanocarriers showed negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys, and spleen. This study provides a simple strategy for the design and fabrication of the BaCO3-based carriers for the development of dual bioimaging.

Kidney dynamic SPECT acquisition on a CZT swiveling-detector ring camera: an in vivo pilot study.

BACKGROUND: Large field of view CZT SPECT cameras with a ring geometry are available for some years now. Thanks to their good sensitivity and high temporal resolution, general dynamic SPECT imaging may be performed more easily, without resorting to dedicated systems. To evaluate the dynamic SPECT imaging by such cameras, we have performed an in vivo pilot study to analyze the kidney function of a pig and compare the results to standard dynamic planar imaging by a conventional gamma camera. METHODS: A 7-week-old (12 kg) female Landrace pig was injected with [99mTc]Tc-MAG3 and a 30 min dynamic SPECT acquisition of the kidneys was performed on a CZT ring camera. A fast SPECT/CT was acquired with the same camera immediately after the dynamic SPECT, without moving the pig, and used for attenuation correction and drawing regions of interest. The next day the same pig underwent a dynamic planar imaging of the kidneys by a conventional 2-head gamma camera. The dynamic SPECT acquisition was reconstructed using a MLEM algorithm with up to 20 iterations, with and without attenuation correction. Time-activity curves of the total counts of each kidney were extracted from 2D and 3D dynamic images. An adapted 2-compartment model was derived to fit the data points and extract physiological parameters. Comparison of these parameters was performed between the different reconstructions and acquisitions. RESULTS: Time-activity curves were nicely fitted with the 2-compartment model taking into account the anesthesia and bladder filling. Kidney physiological parameters were found in agreement with literature values. Good agreement of these parameters was obtained for the right kidney between dynamic SPECT and planar imaging. Regional analysis of the kidneys can be performed in the case of the dynamic SPECT imaging and provided good agreement with the whole kidney results. CONCLUSIONS: Dynamic SPECT imaging is feasible with CZT swiveling-detector ring cameras and provides results in agreement with dynamic planar imaging by conventional gamma cameras. Regional analysis of organs uptake and clearance becomes possible. Further studies are required regarding the optimization of acquisition and reconstruction parameters to improve image quality and enable absolute quantification.

Concordance between vessel-specific and vascular territory coronary functional assessment: A comparison of quantitative flow ratio and myocardial perfusion scintigraphy.

BACKGROUND: Quantitative flow ratio (QFR) and myocardial perfusion scintigraphy (MPS) are utilized for assessing coronary artery disease (CAD) significance. We aimed to analyze their concordance and prognostic impact. AIMS: We aimed to analyze the concordance between QFR and MPS and their risk stratification. METHODS: Patients with invasive coronary angiography and MPS were categorized as concordant if QFR ≤ 0.80 and summed difference score (SDS) ≥ 4 or if QFR > 0.80 and SDS < 4; otherwise, they were discordant. Concordance was classified by coronary territory involvement: total (three territories), partial (two territories), poor (one territory), and total discordance (zero territories). Leaman score assessed coronary atherosclerotic burden. RESULTS: 2010 coronary territories (670 patients) underwent joint QFR and MPS analysis. MPS area under the curve for QFR ≤ 0.80 was 0.637. Concordance rates were total (52.5%), partial (29.1%), poor (15.8%), and total discordance (2.6%). Most concordance occurred in patients without significant CAD or with single-vessel disease (89.5%), particularly without MPS perfusion defects (91.5%). Leaman score (odds ratio [OR]: 0.839, 95% confidence interval [CI]: 0.805-0.875, p < 0.001) and MPS perfusion defect (summed stress score [SSS] ≥ 4) (OR: 0.355, 95% CI: 0.211-0.596, p < 0.001) were independent predictors for discordance. After 1400 days, no significant difference in death/myocardial infarction was observed based on MPS assessment, but Leaman score, functional Leaman score, and average QFR identified higher risk patients. CONCLUSIONS: MPS showed good overall accuracy in assessing QFR significance but substantial discordance existed. Predictors for discordance included higher atherosclerotic burden and MPS perfusion defects (SSS ≥ 4). Leaman score, QFR-based functional Leaman score, and average QFR provided better risk stratification for all-cause death and myocardial infarction than MPS.

Alexander disease with a novel GFAP insertion-deletion mutation mimicking progressive supranuclear palsy.

This report presents a case of Alexander disease showing clinical characteristics mimicking progressive supranuclear palsy (PSP). A 67-year-old woman complaining of motor disturbance exhibited severe atrophy of medulla, spinal cord, and midbrain tegmentum, as well as periventricular hyperintensity on cerebral MRI. Genetic analysis identified a novel in-frame deletion/insertion mutation in the exon 3 of the GFAP gene. Interestingly, neurological findings and decreased striatal uptake in dopamine transporter SPECT were suggestive of PSP. A novel GFAP gene mutation found in the present case may cause the unique clinical phenotype, which should be differentiated from PSP.

Development of a 99mTc-labeled tetrazine for pretargeted SPECT imaging using an alendronic acid-based bone targeting model.

Pretargeting, which is the separation of target accumulation and the administration of a secondary imaging agent into two sequential steps, offers the potential to improve image contrast and reduce radiation burden for nuclear imaging. In recent years, the tetrazine ligation has emerged as a promising approach to facilitate covalent pretargeted imaging due to its unprecedented kinetics and bioorthogonality. Pretargeted bone imaging with TCO-modified alendronic acid (Aln-TCO) is an attractive model that allows the evaluation of tetrazines in healthy animals without the need for complex disease models or targeting regimens. Recent structure-activity relationship studies of tetrazines evaluated important parameters for the design of potent tetrazine-radiotracers for pretargeted imaging. However, limited information is available for 99mTc-labeled tetrazines. In this study, four tetrazines intended for labeling with fac-[99mTc(OH2)3 (CO)3]+ were synthesized and evaluated using an Aln-TCO mouse model. 3,6-bis(2-pyridyl)-1,2,4,5-Tz without additional linker showed higher pretargeted bone uptake and less background activity compared to the same scaffold with a PEG8 linker or 3-phenyl-1,2,4,5-Tz-based compounds. Additionally, improved bone/blood ratios were observed in pretargeted animals compared to animals receiving directly labeled Aln-TCO. The results of this study implicate 3,6-bis(2-pyridyl)-1,2,4,5-Tz as a promising scaffold for potential 99mTc-labeled tetrazines.

Optimizing PSMA scintigraphy for resource limited settings - a retrospective comparative study.

BACKGROUND: PSMA PET/CT is the most sensitive molecular imaging modality for prostate cancer (PCa), yet much of the developing world has little or no access to PET/CT. [99mTc]Tc-PSMA scintigraphy (PS) is a cheaper and more accessible gamma camera-based alternative. However, many resource-constrained departments have only a single camera without tomographic or hybrid imaging functionality, and camera time is frequently in high demand. Simplifying imaging protocols by limiting the field of view (FOV) and omitting SPECT/CT or even SPECT may provide a partial solution. The aim was thus to determine the adequacy of PS planar-only and/or SPECT-only imaging protocols with a limited FOV. METHODS: The scans of 95 patients with histologically proven PCa who underwent PS with full-body planar and multi-FOV SPECT/CT were reviewed. The detection rates for uptake in the prostate gland/bed and in metastases were compared on planar, SPECT, and SPECT/CT. The agreement between modalities was calculated for the detection of metastases and for staging. The impact of imaging a limited FOV was determined. RESULTS: Pathological prostatic uptake was seen in all cases on SPECT/CT (excluding two post-prostatectomy patients), 90.3% of cases on SPECT, and 15.1% on planar images (p < 0.001). Eleven (11.7%) patients had seminal vesicle involvement on SPECT/CT, which was undetectable/indistinguishable on planar images and SPECT. The agreement between modalities was moderate to good (κ = 0.41 to 0.61) for the detection of nodal metastases, with detection rates that did not differ significantly (SPECT/CT = 11.6%, SPECT = 8.4%, planar = 5.3%). Detection rates for bone metastases were 14.7% (SPECT/CT) and 11.6% (SPECT and planar). Agreement between modalities for the detection of bone metastases was good (κ = 0.73 to 0.77). Three (3.1%) patients had visceral metastases on SPECT/CT, two of which were detected on SPECT and planar. There was good agreement between modalities for the TNM staging of patients (κ = 0.70 to 0.88). No metastatic lesions were missed on the limited FOV images. CONCLUSION: When PS scintigraphy is performed, SPECT/CT is recommended. However, the lack of SPECT/CT capabilities should not preclude the use of PS in the presence of limited resources, as both planar and SPECT imaging are adequate and will correctly stage most PCa patients. Furthermore, time-based optimisations are achievable by limiting the FOV to exclude the distal lower limbs.

Robustness of radiomic features in 123I-ioflupane-dopamine transporter single-photon emission computer tomography scan.

Radiomic features are usually used to predict target variables such as the absence or presence of a disease, treatment response, or time to symptom progression. One of the potential clinical applications is in patients with Parkinson's disease. Robust radiomic features for this specific imaging method have not yet been identified, which is necessary for proper feature selection. Thus, we are assessing the robustness of radiomic features in dopamine transporter imaging (DaT). For this study, we made an anthropomorphic head phantom with tissue heterogeneity using a personal 3D printer (polylactide 82% infill); the bone was subsequently reproduced with plaster. A surgical cotton ball with radiotracer (123I-ioflupane) was inserted. Scans were performed on the two-detector hybrid camera with acquisition parameters corresponding to international guidelines for DaT single photon emission tomography (SPECT). Reconstruction of SPECT was performed on a clinical workstation with iterative algorithms. Open-source LifeX software was used to extract 134 radiomic features. Statistical analysis was made in RStudio using the intraclass correlation coefficient (ICC) and coefficient of variation (COV). Overall, radiomic features in different reconstruction parameters showed a moderate reproducibility rate (ICC = 0.636, p <0.01). Assessment of ICC and COV within CT attenuation correction (CTAC) and non-attenuation correction (NAC) groups and within particular feature classes showed an excellent reproducibility rate (ICC > 0.9, p < 0.01), except for an intensity-based NAC group, where radiomic features showed a good repeatability rate (ICC = 0.893, p <0.01). By our results, CTAC becomes the main threat to feature stability. However, many radiomic features were sensitive to the selected reconstruction algorithm irrespectively to the attenuation correction. Radiomic features extracted from DaT-SPECT showed moderate to excellent reproducibility rates. These results make them suitable for clinical practice and human studies, but awareness of feature selection should be held, as some radiomic features are more robust than others.

Preclinical evaluation of Tc-99m p5+14 peptide for SPECT detection of cardiac amyloidosis.

INTRODUCTION: Amyloid deposition is a cause of restrictive cardiomyopathy. Patients who present with cardiac disease can be evaluated for transthyretin (TTR)-associated cardiac amyloidosis using nuclear imaging with 99mTc-labeled pyrophosphate (PYP); however, light chain-associated (AL) cardiac amyloid is generally not detected using this tracer. As an alternative, the amyloid-binding peptide p5+14 radiolabeled with iodine-124 has been shown to be an effective pan-amyloid radiotracer for PET/CT imaging. Here, a 99mTc-labeled form of p5+14 peptide has been prepared to facilitate SPECT/CT imaging of cardiac amyloidosis. METHOD: A synthesis method suitable for clinical applications has been used to prepare 99mTc-labeled p5+14 and tested for peptide purity, product bioactivity, radiochemical purity and stability. The product was compared with99mTc-PYP for cardiac SPECT/CT imaging in a mouse model of AA amyloidosis and for reactivity with human tissue sections from AL and TTR patients. RESULTS: The 99mTc p5+14 tracer was produced with >95% yields in radiopurity and bioactivity with no purification steps required and retained over 95% peptide purity and >90% bioactivity for >3 h. In mice, the tracer detected hepatosplenic AA amyloid as well as heart deposits with uptake ~5 fold higher than 99mTc-PYP. 99mTc p5+14 effectively bound human amyloid deposits in the liver, kidney and both AL- and ATTR cardiac amyloid in tissue sections in which 99mTc-PYP binding was not detectable. CONCLUSION: 99mTc-p5+14 was prepared in minutes in >20 mCi doses with good performance in preclinical studies making it suitable for clinical SPECT/CT imaging of cardiac amyloidosis.

Economic and healthcare resource utilization assessments of PET imaging in Coronary Artery Disease diagnosis: a systematic review and discussion of opportunities for future economic evaluations.

AIMS: This systematic literature review (SLR) consolidated economic and healthcare resource utilization (HCRU) evidence for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to inform future economic evaluations. MATERIALS AND METHODS: An electronic search was conducted in MEDLINE, Embase, and Cochrane databases from 2012-2022. Economic and HCRU studies in adults who underwent PET- or SPECT-MPI for coronary artery disease (CAD) diagnosis were eligible. A qualitative methodological assessment of existing economic evaluations, HCRU, and downstream cardiac outcomes was completed. Exploratory meta-analyses of clinical outcomes were performed. RESULTS: The search yielded 13,439 results, with 71 records included. Economic evaluations and comparative clinical trials were limited in number and outcome types (HCRU, downstream cardiac outcomes, and diagnostic performance) assessed. No studies included all outcome types and only one economic evaluation linked diagnostic performance to HCRU. The meta-analyses of comparative studies demonstrated significantly higher rates of early- and late-invasive coronary angiography and revascularization for PET- compared to SPECT-MPI; however, the rate of repeat testing was lower with PET-MPI. The rate of acute myocardial infarction was lower, albeit non-significant with PET- vs. SPECT-MPI. LIMITATIONS AND CONCLUSIONS: This SLR identified economic and HCRU evaluations following PET- and SPECT-MPI for CAD diagnosis and determined that existing studies do not capture all pertinent outcome parameters or link diagnostic performance to downstream HCRU and cardiac outcomes, thus, resulting in simplified assessments of CAD burden. A limitation of this work relates to heterogeneity in study designs, patient populations, and follow-up times of existing studies. Resultingly, it was challenging to pool data in meta-analyses. Overall, this work provides a foundation for the development of comprehensive economic models for PET- and SPECT-MPI in CAD diagnosis, which should link diagnostic outcomes to HCRU and downstream cardiac events to capture the full CAD scope.

Feasibility Study of Single-Photon Emission Computed Tomography with Iodine-123 Labeled Metaiodobenzylguanidine for Preclinical Evaluation of Labetalol as a ß-Adrenergic Receptor Blocker.

Among clinically used radiopharmaceuticals, iodine-123 labeled metaiodobenzylguanidine ([123I]mIBG) serves for diagnosing neuroendocrine tumors and obtaining images of myocardial sympathetic innervation. mIBG, a structural analogue of norepinephrine (NE), a neurotransmitter acting in peripheral and central nerves, follows a pathway similar to NE, transmitting signals through the NE transporter (NET) located at synaptic terminals. It moves through the body without decomposing, enabling noninvasive image evaluation. In this study, we aimed to quantify [123I]mIBG uptake in the adrenal glands using small animal single-photon emission computed tomography/computed tomography (SPECT/CT) images post [123I]mIBG administration. We investigated the possibility of assessing the effectiveness of ß-adrenergic receptor blockers by quantifying SPECT/CT images and biodistribution results to determine the degree of [123I]mIBG uptake in the adrenal glands treated with labetalol, a known ß-adrenergic receptor blocker. Upon intravenous administration of [123I]mIBG to mice, SPECT/CT images were acquired over time to confirm the in vivo distribution pattern, revealing a clear uptake in the adrenal glands. Labetalol inhibited the uptake of [123I]mIBG in cell lines expressing NET. A decrease in [123I]mIBG uptake in the adrenal glands was observed in the labetalol-treated group compared with the normal group through SPECT/CT imaging and biodistribution studies. These results demonstrate that SPECT/CT imaging with [123I]mIBG could be applicable for evaluating the preclinical efficacy of new antihypertensive drug candidates such as labetalol, a ß-adrenergic receptor blocker.

ISIT-QA: In Silico Imaging Trial to Evaluate a Low-Count Quantitative SPECT Method Across Multiple Scanner-Collimator Configurations for 223Ra-Based Radiopharmaceutical Therapies.

Personalized dose-based treatment planning requires accurate and reproducible noninvasive measurements to ensure safety and effectiveness. Dose estimation using SPECT is possible but challenging for alpha (α)-particle-emitting radiopharmaceutical therapy (α-RPT) because of complex γ-emission spectra, extremely low counts, and various image-degrading artifacts across a plethora of scanner-collimator configurations. Through the incorporation of physics-based considerations and skipping of the potentially lossy voxel-based reconstruction step, a recently developed projection-domain low-count quantitative SPECT (LC-QSPECT) method has the potential to provide reproducible, accurate, and precise activity concentration and dose measures across multiple scanners, as is typically the case in multicenter settings. To assess this potential, we conducted an in silico imaging trial to evaluate the LC-QSPECT method for a 223Ra-based α-RPT, with the trial recapitulating patient and imaging system variabilities. Methods: A virtual imaging trial titled In Silico Imaging Trial for Quantitation Accuracy (ISIT-QA) was designed with the objectives of evaluating the performance of the LC-QSPECT method across multiple scanner-collimator configurations and comparing performance with a conventional reconstruction-based quantification method. In this trial, we simulated 280 realistic virtual patients with bone-metastatic castration-resistant prostate cancer treated with 223Ra-based α-RPT. The trial was conducted with 9 simulated SPECT scanner-collimator configurations. The primary objective of this trial was to evaluate the reproducibility of dose estimates across multiple scanner-collimator configurations using LC-QSPECT by calculating the intraclass correlation coefficient. Additionally, we compared the reproducibility and evaluated the accuracy of both considered quantification methods across multiple scanner-collimator configurations. Finally, the repeatability of the methods was evaluated in a test-retest study. Results: In this trial, data from 268 223RaCl2 treated virtual prostate cancer patients, with a total of 2,903 lesions, were used to evaluate LC-QSPECT. LC-QSPECT provided dose estimates with good reproducibility across the 9 scanner-collimator configurations (intraclass correlation coefficient > 0.75) and high accuracy (ensemble average values of recovery coefficients ranged from 1.00 to 1.02). Compared with conventional reconstruction-based quantification, LC-QSPECT yielded significantly improved reproducibility across scanner-collimator configurations, accuracy, and test-retest repeatability ([Formula: see text] Conclusion: LC-QSPECT provides reproducible, accurate, and repeatable dose estimations in 223Ra-based α-RPT as evaluated in ISIT-QA. These findings provide a strong impetus for multicenter clinical evaluations of LC-QSPECT in dose quantification for α-RPTs.

Synthesis and Evaluation of Radiogallium Labeled Bone-Imaging Probes Using Oligo-γ-Carboxy Glutamic Acid Peptides as Carriers to Bone.

We investigated the importance of the carboxy group density in bone affinity during the development of peptide-based bone-seeking radiopharmaceuticals and carriers. Oligo-γ-carboxy glutamic acid peptides [(Gla)n] with higher carboxy group density than oligo-glutamic acid peptides [(Glu)n] and oligo-aspartic acid peptides [(Asp)n] were chosen. Using the radiogallium chelator N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC), we synthesized [67Ga]Ga-HBED-CC-(Gla)n (n = 1, 2, 5, 8, 11, or 14) with high yields. Hydroxyapatite-binding assays, biodistribution, and SPECT imaging showed higher affinity and bone accumulation for [67Ga]Ga-HBED-CC-(Gla)n compared to [67Ga]Ga-HBED-CC-(Glu)n. Notably, [67Ga]Ga-HBED-CC-(Gla)8 and [67Ga]Ga-HBED-CC-(Gla)11 exhibited superior bone accumulation and rapid blood clearance. SPECT/CT imaging with [67Ga]Ga-HBED-CC-(Gla)8 exclusively visualized the bone tissue. These findings support the potential use of [67Ga]Ga-HBED-CC-(Gla)n as excellent bone-imaging PET probes, suggesting (Gla)n peptides are superior bone-seeking carriers.

Sarcopenia does not affect liver regeneration and postoperative course after a major hepatectomy. A prospective study on 125 patients using CT volumetry and HIDA scintigraphy.

BACKGROUND & OBJECTIVES: Sarcopenia is a morbi-mortality risk factor in digestive surgery, though its impact after major hepatectomy (MH) remains unknown. This prospective pilot study investigated whether volume and function of a regenerating liver is influenced by body composition. METHODS: From 2011 to 2016, 125 consecutive patients had computed tomography and 99mTc-labelled-mebrofenin SPECT-scintigraphy before and after MH at day 7 and 1 month for measurements of liver volumes and functions. L3 vertebra muscle mass identified sarcopenia. Primary endpoint was the impact of sarcopenia on regeneration capacities (i.e. volume/function changes and post-hepatectomy liver failure (PHLF) rate). Secondary endpoint was 3-month morbi-mortality. RESULTS: Sarcopenic patients (SP; N = 69) were significantly older than non-sarcopenic (NSP), with lower BMI and more malignancies, but with comparable liver function/volume at baseline. Postoperatively, SP showed higher rates of ISGLS_PHLF (24.6 % vs 10.9 %; p = 0.05) but with comparable rates of severe morbidity (23.2 % vs 16.4 %; p = 0.35), overall (8.7 % vs 3.6 %; p = 0.3) and PHLF-related mortality (8,7 % vs 1.8 %; p = 0.075). After matching on the extent of resection or using propensity score, regeneration and PHLF rates were similar. CONCLUSION: This prospective study using first sequential SPECT-scintigraphy showed that sarcopenia by itself does not affect liver regeneration capacities and short-term postoperative course after MH.

Dopaminergic dysfunction in the left putamen of patients with major depressive disorder.

INTRODUCTION: Dopaminergic transmission impairment has been identified as one of the main neurobiological correlates of both depression and clinical symptoms commonly associated with its spectrum such as anhedonia and psychomotor retardation. OBJECTIVES: We examined the relationship between dopaminergic deficit in the striatum, as measured by 123I-FP-CIT SPECT imaging, and specific psychopathological dimensions in patients with major depressive disorder. METHODS: To our knowledge this is the first study with a sample of >120 subjects. After check for inclusion and exclusion criteria, 121 (67 females, 54 males) patients were chosen retrospectively from an extensive 1106 patients database of 123I-FP-CIT SPECT scans obtained at the Nuclear Medicine Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome. These individuals had undergone striatal dopamine transporter (DAT) assessments based on the recommendation of their referring clinicians, who were either neurologists or psychiatrists. At the time of SPECT imaging, each participant underwent psychiatric and psychometric evaluations. We used the following psychometric scales: Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Snaith Hamilton Pleasure Scale, and Depression Retardation Rating Scale. RESULTS: We found a negative correlation between levels of depression (p = 0.007), anxiety (p = 0.035), anhedonia (p = 0.028) and psychomotor retardation (p = 0.014) and DAT availability in the left putamen. We further stratified the sample and found that DAT availability in the left putamen was lower in seriously depressed patients (p = 0.027) and in patients with significant psychomotor retardation (p = 0.048). CONCLUSION: To our knowledge this is the first study to have such a high number of sample. Our study reveals a pivotal role of dopaminergic dysfunction in patients with major depressive disorder. Elevated levels of depression, anxiety, anhedonia, and psychomotor retardation appear to be associated with reduced DAT availability specifically in the left putamen.

Tumor-Induced Parkinsonism Due to a Large Meningioma Diagnosed by 99m Tc-TRODAT-1 SPECT/CT.

ABSTRACT: A 67-year-old woman complained of rest and postural tremors in her left upper extremity, associated with bradykinesia and gait disorder since 2 years ago, with no significant response to antiparkinsonism drugs. Dopamine transporter SPECT/CT revealed a remarkable area of 99m Tc-TRODAT-1 uptake in a huge tumoral lesion in the right frontotemporal region, compressing and dislocating the right striatum with evidence of significant midline shift. The patient underwent surgical resection with a diagnosis of meningioma on preoperative MRI and postoperative histology report, experiencing a marked recovery in symptoms after 1 month.

Dynamic multi-pinhole collimated brain SPECT of Parkinson's disease by [123I]FP-CIT: a feasibility study of fSPECT.

We investigated the feasibility of using a dopamine transporter (DaT) tracer ligand ([123I]FP-CIT) along with novel multi-pinhole brain collimators for dynamic brain single photon emission computed tomography (SPECT) in suspected Parkinson's disease patients. Thirteen patients underwent dynamic tracer acquisitions before standard imaging. Uptake values were corrected for partial volume effects. Specific binding ratio (SBRcalc) was calculated, reflecting binding potential relative to non-displaceable binding (BPND) in the cortex. Additional pharmacokinetic parameters (BPND, R1, k2) were estimated using the simplified reference tissue model, revealing differences between Kahraman low-score (LS) and high-score (HS) groups. Results showed increasing striatal tracer uptake until 100 min post-injection, with consistent values afterward. Uptake and SBRcalc ratios matched visual assessment. LS patients had lower putamen than caudate nucleus tracer uptake, decreased BPND values, while R1 and k2 values were comparable to HS patients. In conclusion, dynamic multi-pinhole SPECT using DaT tracer with the extraction of pharmacokinetic parameters is feasible and could help enable early differentiation of reduced and normal DaT values.

Dosimetry during iodine-131 therapy - a technical point of view from a single centre's own experience.

BACKGROUND: Nuclear medicine uses radionuclides in medicine for diagnosis, staging, therapy, and monitoring the response to therapy. The application of radiopharmaceutical therapy for the treatment of certain diseases is well-established, and the field is expanding. Internal dosimetry is multifaceted and includes different workflows, as well as various calculations based on patient- specific dosimetry. AIM: The objective of this study was to introduce the technical issues which might occur during iodine-131 (¹³¹I) dosimetry performed in nuclear medicine departments. MATERIAL AND METHODS: Retrospective analysis was performed on a group of 44 patients with papillary thyroid cancer who between May 2021 and October 2021 underwent a 131I treatment: 80-100 mCi (2200-3700 MBq, based on the previous medical history and stage of the disease). Patients underwent a series of ¹³¹I therapy scans using gamma camera Discovery NM 670 CT. Whole body scan (WBS) was performed 2, 4, 24 and 48 hours after ¹³¹I administration. Additionally, after 24 hours of single photon emission computed tomography/ computed tomography, two fields of view (SPECT/CT 2-FOV) were performed from the mid-head to the bladder. RESULTS: During the dosimetry procedure, several issues arise. Firstly, after receiving therapeutic doses of ¹³¹I, patients should remain in their rooms until the appropriate activity is achieved before being transported to the diagnostic room. Secondly, the walls between examination rooms meet the requirements for accurate diagnosis but not for therapy, leading to the occurrence of artefacts in patients examined behind the wall, potentially influencing the examination results. Thirdly, personnel in the control room also experience additional exposure (10 times greater than in the case of standard diagnostic procedure). CONCLUSIONS: The dosimetry in patients in whom therapeutic procedures are performed with the use of isotopes is mandatory according to Polish and European law, technical issues which occur during the dosimetry procedures might influence the organization of the work in departments.