SPECT Imaging Research Articles

Thymidine Phosphorylase Imaging Probe for Differential Diagnosis of Metabolic dysfunction-associated Steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises simple steatosis (SS), which has a low risk of mortality, and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to liver cirrhosis and hepatocellular carcinoma. Because differentiation between MASH and SS is the most important issue in the diagnosis of MASLD, the establishment of noninvasive diagnostic methods is urgently needed. In this study, we evaluated the potential of [123I]IIMU, a thymidine phosphorylase (TYMP) targeted SPECT imaging probe, for differential diagnosis of MASLD in a preclinical animal model. SS and MASH mice were prepared by feeding db/db mice with a standard diet and a methionine/choline-deficient diet, respectively. Control mice were prepared by feeding m/m mice with a standard diet. TYMP expression in the liver was evaluated by RT-PCR, western blotting, and immunohistochemistry. The biodistribution of [125I]IIMU in the three model mice was evaluated at 30min post-injection. SPECT/CT imaging studies of the three model mice were performed 30min after injection of [123I]IIMU. Hepatic TYMP expression level was the highest in the SS mice and the lowest in the MASH mice at both mRNA and protein levels. The immunohistochemistry experiment showed a patchy distribution of TYMP only in the liver of MASH mice. In the biodistribution study, the hepatic accumulation of [125I]IIMU was the highest in the SS mice and the lowest in the MASH mice. The SPECT/CT imaging study showed similar results to the biodistribution experiment. Hepatic TYMP expression level may serve as a promising imaging biomarker for differential diagnosis of SS and MASH. SPECT imaging using [123I]IIMU potentially provides a novel noninvasive diagnostic method to differentiate MASH and SS.

Comparison of the dosimetry and cell survival effect of 177Lu and 161Tb somatostatin analog radiopharmaceuticals in cancer cell clusters and micrometastases.

177Lu-based radiopharmaceuticals (RPs) are the most used for targeted radionuclide therapy (TRT) due to their good response rates. However, the worldwide availability of 177Lu is limited. 161Tb represents a potential alternative for TRT, as it emits photons for SPECT imaging, β--particles for therapy, and also releases a significant yield of internal conversion (IE) and Auger electrons (AE). This research aimed to evaluate cell dosimetry with the MIRDcell code considering a realistic localization of three 161Tb- and 177Lu-somatostatin (SST) analogs in different subcellular regions as reported in the literature, various cell cluster sizes (25-1000µm of radius) and percentage of labeled cells. Experimental values of the α- and β-survival coefficients determined by external beam photon irradiation were used to estimate the survival fraction (SF) of AR42J pancreatic cell clusters and micrometastases. The different localization of RPs labeled with the same radionuclide within the cells, resulted in only slight variations in the dose absorbed by the nuclei (ADN) of the labeled cells with no differences observed in either the unlabeled cells or the SF. ADN of labeled cells (MDLC) produced by 161Tb-RPs were from 2.8-3.7 times higher than those delivered by 177Lu-RPs in cell clusters with a radius lower than 0.1mm and 10% of labeled cells, due to the higher amount of energy emitted by 161Tb-disintegration in form of IE and AE. However, the 161Tb-RPs/177Lu-RPs MDLC ratio decreased below 1.6 in larger cell clusters (0.5-1mm) with > 40% labeled cells, due to the significantly higher 177Lu-RPs cross-irradiation contribution. Using a fixed number of disintegrations, SFs of 161Tb-RPs in clusters with > 40% labeled cells were lower than those of 177Lu-RPs, but when the same amount of emitted energy was used no significant differences in SF were observed between 177Lu- and 161Tb-RPs, except for the smallest cluster sizes. Despite the emissions of IE and AE from 161Tb-RPs, their localization within different subcellular regions exerted a negligible influence on the ADN. The same cell damage produced by 177Lu-RPs could be achieved using smaller quantities of 161Tb-RPs, thus making 161Tb a suitable alternative for TRT.

Partial volume correction for Lu-177-PSMA SPECT.

The limited spatial resolution in SPECT images leads to partial volume effect (PVE), degrading the subsequent dosimetric accuracy. We aim to quantitatively evaluate PVE and partial volume corrections (PVC), i.e., recovery coefficient (RC)-PVC (RC-PVC), reblurred Van-Cittert (RVC) and iterative Yang (IY), in 177Lu-PSMA-617 SPECT images. We employed a geometrical cylindrical phantom containing five spheres (diameters ranging from 20 to 40mm) and 40 XCAT phantoms with various anatomical variations and activity distributions. SIMIND Monte Carlo code was used to generate realistic noisy projections. In the clinical study, sequential quantitative SPECT/CT imaging at 4 time-points post 177Lu-PSMA-617 injections were analyzed for 10 patients. Iterative statistical reconstruction methods were used for reconstruction with attenuation, scatter and geometrical collimator detector response corrections, followed by post-filters. The RC-curves were fit based on the geometrical phantom study and applied for XCAT phantom and clinical study in RC-PVC. Matched and 0.5-2.0 voxels (2.54-10.16mm) mismatched sphere masks were deployed in IY. The coefficient of variation (CoV) was measured on a uniform background on the geometrical phantom. RCs of spheres and mean absolute activity error (MAE) of kidneys and tumors were evaluated in simulation data, while the activity difference was evaluated in clinical data before and after PVC. In the simulation study, the spheres experienced significant PVE, i.e., 0.26 RC and 0.70 RC for the 20mm and 40mm spheres, respectively. RVC and IY improved the RC of the 20mm sphere to 0.37 and 0.75 and RC of the 40mm sphere to 0.96 and 1.04. Mismatch in mask increased the activity error for all spheres in IY. RVC increased noise and caused Gibbs ringing artifacts. For XCAT phantoms, both RVC and IY performed comparably and were superior to RC-PVC in reducing the MAE of the kidneys. However, IY and RC-PVC outperformed RVC for tumors. The XCAT phantom study and clinical study showed a similar trend in the kidney and tumor activity differences between non-PVC and PVC. PVE greatly impacts activity quantification, especially for small objects. All PVC methods improve the quantification accuracy in 177Lu-PSMA SPECT.

Investigation of scatter energy window width and count levels for deep learning-based attenuation map estimation in cardiac SPECT/CT imaging

Objective.Deep learning (DL) is becoming increasingly important in generating attenuation maps for accurate attenuation correction (AC) in cardiac perfusion SPECT imaging. Typically, DL models take inputs from initial reconstructed SPECT images, which are performed on the photopeak window and often also on scatter windows. While prior studies have demonstrated improvements in DL performance when scatter window images are incorporated into the DL input, the comprehensive analysis of the impact of employing different scatter windows remains unassessed. Additionally, existing research mainly focuses on applying DL to SPECT scans obtained at clinical standard count levels. This study aimed to assess utilities of DL from two aspects: (1) investigating the impact when different scatter windows were used as input to DL, and (2) evaluating the performance of DL when applied on SPECT scans acquired at a reduced count level.Approach.We utilized 1517 subjects, with 386 subjects for testing and the remaining 1131 for training and validation.Main results.The results showed that as scatter window width increased from 4% to 30%, a slight improvement was observed in DL estimated attenuation maps. The application of DL models to quarter-count (¼-count) SPECT scans, compared to full-count scans, showed a slight reduction in performance. Nonetheless, discrepancies across different scatter window configurations and between count levels were minimal, with all normalized mean square error (NMSE) values remaining within 2.1% when comparing the different DL attenuation maps to the reference CT maps. For attenuation corrected SPECT slices using DL estimated maps, NMSE values were within 0.5% when compared to CT correction.Significance.This study, leveraging an extensive clinical dataset, showed that the performance of DL seemed to be consistent across the use of varied scatter window settings. Moreover, our investigation into reduced count studies indicated that DL could provide accurate AC even at a ¼-count level.

Exploring a tristhione scorpionate ligand as a suitable chelator for the theranostic pair antimony-119 and antimony-117

BackgroundThe highly potent Auger electron emitter antimony-119 (119Sb) and the SPECT-isotope antimony-117 (117Sb) comprise a true theranostic pair particularly suitable for cancer theranostics. Harnessing this potential requires development of a chelator that can rapidly form a stable complex with radioactive antimony ions at the low concentrations typical of radiopharmaceutical preparations. Stable Sb(III) complexes of hydrotris(methimazolyl)borate (TMe) are known, prompting our investigation of this chelator. Additionally, the production of radioantimony was optimized and the SPECT imaging properties of 117Sb was investigated, in an attempt to move towards biomedical implementation of the theranostic isotope pair of antimony.ResultsA method for rapid and effective labelling of TMe using 117Sb was developed, yielding high radiochemical purities of 98.5 ± 2.7% and high radionuclidic purities exceeding 99%. Radiolabelling yielded an Sb(III) complex directly from the acidic Sb(V) solution. [1XXSb]Sb-TMe in aqueous acidic solution showed high stability in the presence of cysteine, however, the stability of the radiocomplex at increased pH was significantly decreased. The production method of 117Sb was optimized, enabling a production yield of up to 19.6 MBq/µAh and the production of up to 564 MBq at end of bombardment, following irradiation of a thin 117Sn-enriched solid target. Preclinical SPECT/CT scanning of a mouse phantom containing purified 117Sb demonstrated excellent SPECT imaging properties of 117Sb with high spatial resolution comparable to that of technetium-99m.ConclusionWe have explored the TMe chelator for complexation of radioantimony and devised a rapid chelation protocol suitable for the short half-life of 117Sb (T1/2 = 2.8 h). [1XXSb]Sb-TMe (1XXSb = 117Sb, 118mSb, 120mSb and 122Sb) demonstrated a high stability in presence of cysteine, although low stability was observed at pH > 4. We have achieved a production yield of 117Sb high enough for clinical applications and demonstrated the excellent SPECT-imaging properties of 117Sb. The results contribute valuable information for the development of suitable chelators for radioantimony and is a step further towards implementation of the antimony theranostic pair in biomedical applications.

New Horizons in Nuclear Cardiology: Imaging of Peripheral Arterial Disease.

Lower extremity peripheral artery disease (PAD) is characterized by impairment of blood flow associated with arterial stenosis and frequently coexisting microvascular disease and is associated with high rates of morbidity and mortality. Current diagnostic modalities have limited accuracy in early diagnosis, risk stratification, preprocedural assessment, and evaluation of therapy and are focused on the detection of obstructive atherosclerotic disease. Early diagnosis and assessment of both large vessels and microcirculation may improve risk stratification and guide therapeutic interventions. SPECT and PET imaging have been shown to be accurate to detect changes in perfusion in preclinical models and clinical disease, and have the potential to overcome limitations of existing diagnostic modalities, while offering novel information about perfusion, metabolic, and molecular processes. This review provides a comprehensive reassessment of radiotracer-based imaging of PAD in preclinical and clinical studies, emphasizing the challenges that arise due to the complex physiology in the peripheral vasculature. We will also highlight the latest advancements, underscoring emerging artificial intelligence and big data analysis, as well as clinically relevant areas where the field could advance in the next decade.

Safety and Feasibility of Interventional Hybrid Fluoroscopy and Nuclear Imaging in the Work-up Procedure of Hepatic Radioembolization.

Purpose To evaluate the safety and feasibility of a novel hybrid nuclear and fluoroscopy C-arm scanner to be used during the work-up procedure of hepatic radioembolization. Materials and Methods In this prospective first-in-human clinical study, 12 participants (median age, 67 years [range: 37-78 years]; nine [75%] male, three [25%] female) with liver tumors undergoing work-up for yttrium 90 radioembolization were included (ClinicalTrials.gov NCT06013774). Work-up angiography and technetium 99m-macroaggregated albumin injection were performed in an angiography suite equipped with a hybrid C-arm that could simultaneously perform fluoroscopy and planar nuclear imaging. Technetium 99m-macroaggregated albumin was injected under real-time hybrid imaging, followed by in-room SPECT imaging. Safety and feasibility were studied by assessing adverse events, technical performance, additional x-ray radiation dose, and questionnaires completed by radiologists and technologists. Results No adverse events were attributed to the hybrid C-arm scanner. The additional x-ray radiation dose was low (median, 19 Gy · cm2; minimum: 12 Gy · cm2; maximum: 21 Gy · cm2 for participants who completed all imaging steps). The interventional personnel considered use of the hybrid C-arm scanner safe and feasible, although the additional time spent in the intervention room was considered long (median, 64 minutes; minimum: 55 minutes; maximum: 77 minutes for participants who completed all imaging steps). Conclusion Use of the hybrid C-arm scanner during the work-up procedure of hepatic radioembolization was found to be safe and feasible in this first-in-human clinical study. Keywords: Angiography, Fluoroscopy, Interventional-Vascular, Radionuclide Studies, Radiosurgery, Gamma Knife, Cyberknife, SPECT, Instrumentation, Physics, Technical Aspects, Technology Assessment Supplemental material is available for this article. Published under a CC BY 4.0 license. Clinical trial registration no. NCT06013774.

Different PSMA Radiopharmaceuticals: A Comparative Study of [18F]F-PSMA-1007, [18F]F-JK-PSMA-7, and [99mTc]Tc-PSMA-I&S in the Skeletal System

Background: Numerous PSMA-based tracers are used for diagnostic prostate cancer imaging, but comprehensive comparisons between multiple ligands are lacking. This study aimed to compare physiological skeletal uptake and tracer uptake in commonly recommended PSMA reference regions across three different PSMA ligands in prostate cancer patients. Methods: A total of 281 prostate cancer patients were included. Using PET and SPECT imaging, target volumes of interest were defined via a semiautomatic method, and standardized uptake values (SUV) were calculated for the skeletal system and reference regions (liver, spleen, parotid gland, and blood pool). Results: Significant differences in SUV uptake were observed, with [18F]F-PSMA-1007 showing higher SUV values in the skeletal system. The parotid gland displayed the highest variability in uptake, while the blood pool and liver exhibited more homogeneous uptake across patients. Conclusions: While radioligands behave similarly in bone regions, there are notable differences in SUV patterns, particularly for PSMA-1007, which showed higher bone uptake. Parotid gland uptake variability suggests a reconsideration of its suitability as a reference region, while the liver, spleen, and blood pool showed more consistent uptake. During comparison, the technetium-labeled SPECT ligand proved as similarly effective as the two PET ligands for diagnostic imaging.

Remote ischemic peri-conditioning suppressed cardiac sympathetic nerve activity especially in the non-culprit lesion in patients with acute myocardial infarction

Abstract Background Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). However, it remains to be elucidated whether RIPC affects the cardiac sympathetic nerve activity in patients with AMI. Purpose The purpose of this study is to investigate the effect of RIPC on cardiac sympathetic nerve activity (CSNA) in the culprit and non-culprit lesion respectively in patients with AMI. Methods We randomly assigned 157 patients with suspected AMI undergoing emergent PCI to receive transient limb ischemia (by inflating a cuff at 200 mmHg for 4×5 minutes: RIPC group, n=77) or no procedure (control group, n=80). After excluding inappropriate patients such as those with other diagnosis than AMI, we analyzed 122 patients (62 patients in RIPC and 60 in control group). CSNA was assessed in the culprit and non-culprit lesion respectively by the cardiac MIBG SPECT imaging. Results Patients in RIPC and control group had similar demographic and clinical characteristics at baseline. Patients in RIPC group tended to show higher late uptake only in the non-culprit lesion at discharge. At 1 year after discharge, patients in RIPC group demonstrated significantly higher late uptake (p=0.021) and lower washout rate (p=0.013) than those in control group in the non-culprit lesion. Regarding the culprit lesion, only washout rate tended to be lower in RIPC group at 1 year after discharge. Conclusion(s): Remote ischemic peri-conditioning showed suppressive effect on cardiac sympathetic nerve activity especially in the non-culprit lesion in patients with acute myocardial infarction.SPECT parameters in RIPC and control

Catheter ablation increases cerebral blood flow and cognitive function in elderly patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) has been considered to have an increased risk for cognitive impairment independent of a stroke and a silent micro-infarction. The mechanism of this interaction is unclear. One of the potential explanations is brain hypoperfusion due to a reduced cardiac output. To date, there are no reports focusing on the cerebral blood flow and cognitive impairment in patients undergoing AF ablation. Purpose The purpose of this study was to investigate whether catheter ablation of AF would increase cerebral blood flow and restore cognitive impairment. Methods AF patients aged 75 years or older with mild or more cognitive impairment were selected. The assessment of cognitive function using Mini-Mental State Examination (MMSE) and Hasegawa's Dementia Scale-Revised (HDS-R), and measurement of cerebral blood flow using 99mTc-ECD SPECT imaging were examined before and 3 months after ablation. Results A total of 25 elderly patients (mean age 83, 14 males and 11 females) were included in this study. Of them, 23 patients had persistent AF. Twenty-three patients (92%) maintained sinus rhythm after ablation. There was a significant improvement in MMSE score (from 24.6±4.5 to 25.9±4.0, p<0.05) and HDS-R (from 23.2±5.5 to 24.8±5.1, p<0.05) after ablation. Cerebral blood flow also significantly increased after ablation (right lobe: from 34.4±4.6 to 38.5±4.4 ml/100g/min, p<0.01, left lobe: from 35.3±9.7 to 38.8±3.7 ml/100g/min, p<0.01). Overall average cerebral blood flow increased by 10.1±9.4% after ablation. There was a positive correlation between the changes in MMSE score and the changes in cerebral blood flow (r=0.65, p<0.05). Conclusion AF ablation in elderly patients increased cerebral blood flow and cognitive function. AF ablation would be one of the therapeutic options to improve cognitive function in elderly patients with cognitive impairment.

The activation of cardiac sympathetic nervous system in the non-culprit lesion is a strong prognostic predictor in patients with acute myocardial infarction

Abstract Background The activation of cardiac sympathetic nervous system is associated with poor prognosis in patients with acute myocardial infarction (AMI). However, it remains to be determined whether regional assessment of cardiac sympathetic nerve activity (CSNA) in the culprit and non-culprit lesion of the cardiac MIBG SPECT imaging could have prognostic value in patients with AMI. Purpose The purpose of this study is to investigate the prognostic impact of regional CSNA in patients with AMI. Methods We prospectively enrolled 122 patients with AMI who visited our emergency department and underwent primary percutaneous coronary intervention. The late heart-to-mediastinum ratio (HMR) and washout rate (WR) was calculated to assess CSNA in the whole heart from planar images of in the cardiac MIBG imaging. The MIBG SPECT image parameters were calculated for each coronary artery, and the average WR in the culprit and non-culprit lesion were evaluated to assess the regional status of CSNA in patients with AMI. Abnormal WR in planar image was defined as 34% or more, as previously reported. The cut-off value of late HMR in planar image, WR in the culprit and non-culprit lesions were determined by ROC analysis. The primary endpoint was major adverse cardiac event (MACE) including all cause death, myocardial infarction, hospitalization for heart failure and target lesion revascularization. Results During a mean follow-up period of 3.1±1.8 years, 25 of 122 patients underwent MACE. The late HMR (p=0.004), WR in planar image (p=0.002), WR in the culprit lesion (p=0.023), and WR in the non-culprit lesion (p<0.001) were significantly associated with MACE at univariate Cox proportional hazard analysis. The increased WR in the non-culprit lesion (defined as 28.3% or more: AUC 0.697 [0.576-0.817]) was significantly independently associated with MACE (hazard ratio: 4.36 [1.45-13.11], p=0.009) even adjusted by late HMR, WR in planar image or WR in the culprit lesion, while decreased HMR, abnormal WR in planar image and increased WR in the culprit lesion showed no significant association with MACE in the multivariate model with WR in the non-culprit lesion. Kaplan-Meier analysis revealed that patients with increased WR in the non-culprit lesion had significantly higher risk for MACE than those without increased WR (45% vs 11% p<0.001). Conclusion(s) The activation of cardiac sympathetic nervous system in the non-culprit lesion is particularly associated with poor prognosis in patients with acute myocardial infarction.MACE risk by WR in non-culprit lesion

Perfusion metabolism mismatch predicts short-term complications in Takotsubo syndrome

Abstract Background Takotsubo syndrome (TTS) is a transient cardiac condition triggered by sudden emotional or physical stress characterized by LV dysfunction in the absence of obstructive epicardial coronary artery disease. 123I-BMIPP, an iodinated fatty acid analogue, can identify impaired myocardial metabolic activity. With the use of dual SPECT protocol, reduced uptake of 123I-BMIPP compared to perfusion which is called perfusion-metabolic mismatch is observed in apical regions in TTS. The mismatch may indicate jeopardized but viable myocardium, reflecting transient ischemic damage or metabolically stunned myocardium. However, the association between the perfusion metabolism mismatch in TTS and its complications remains underexplored. Purpose Our study aimed to analyze the degree of perfusion metabolism mismatch at the acute phase in TTS and investigate its association with short-term complications. Methods This retrospective study conducted between 2012 and 2024 at a single center included 82 patients diagnosed with TTS. Patients underwent dual SPECT imaging using 99mTc or 201 Tl and 123I-BMIPP within two weeks of admission. We applied quantitative analysis using QGS/QPS software from Cedars-Sinai. Total perfusion deficit ("TPD") was calculated based on sex-matched normal limits providing the extent of perfusion abnormality. Meanwhile, perfusion-metabolism mismatch scores ("worsen") were determined by comparing the total BMIPP counts to the total counts of perfusion. We then assessed the correlation of these imaging findings with biomarkers, regional wall motion abnormalities, and the occurrence of short-term complications. Short-term complications included heart failure, left ventricular outflow (LVOT) obstruction, mitral regurgitation, cardiac arrhythmia, cardiogenic shock, left ventricle (LV) rupture, and cardiac death during the hospitalization period. Results All study patients exhibited wall motion abnormalities seen in apical segments. The count of myocardial segments with regional wall motion abnormality was correlated with both TPD (r=0.34, p=0.002) and perfusion metabolic mismatch score (r=0.40, p<0.001). TPD had a moderate correlation coefficient with max CK-MB (r=0.44, p<0.001) and troponin T (r=0.40, p<0.001) levels. However, perfusion metabolic mismatch did not display correlations with max CK-MB (r=0.05, p=0.65), and Troponin T (r=0.12, p=0.28) levels. Among 82 patients, 37 patients experienced any short-term complications. Importantly, patients with short-term complications had elevated perfusion mismatch scores compared to those without short-term complications (14.0 [6.0-22.5] vs. 5.0 [3.0-10.0], p<0.001). However, no significant difference was observed in TPD between the two groups (9.0 [4.5-20.0] vs. 7.0 [3.0-12.0], p=0.130). Conclusions Our research highlights a significant association between perfusion-metabolism mismatch and an increased risk for short-term complications in patients with Takotsubo syndrome.

Synthesis and Evaluation of 68Ga- and 177Lu-Labeled [Pro14]bombesin(8-14) Derivatives for Detection and Radioligand Therapy of Gastrin-Releasing Peptide Receptor-Expressing Cancer.

The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of cancers and represents a promising target for diagnosis and therapy. However, the extremely high accumulation in the pancreas observed for most of the clinically evaluated GRPR-targeted radiopharmaceuticals could limit their applications. In this study, we synthesized one GRPR antagonist (ProBOMB5) and two GRPR agonists (LW02056 and LW02057) by replacing the 4-thiazolidinecarboxylic acid (Thz14) residue in our previously reported GRPR-targeted tracers with Pro14. The 68Ga and 177Lu labeling were conducted in HEPES (2 M, pH 5.0) buffer and acetate (0.1 M, pH 4.5) buffer, respectively, and the radiolabeled products were obtained in a 24-57% decay-corrected radiochemical yield and >92% radiochemical purity. The binding affinities (Ki) of Ga-ProBOMB5, Ga-LW02056, Ga-LW02057, and Lu-ProBOMB5 were measured via in vitro competition binding assays and were 12.2 ± 1.89, 14.7 ± 4.81, 13.8 ± 2.24, and 13.6 ± 0.25 nM, respectively. The PET imaging and ex vivo biodistribution studies were conducted in PC-3 tumor-bearing mice at 1 h post injection. [68Ga]Ga-ProBOMB5, [68Ga]Ga-LW02056, and [68Ga]Ga-LW02057 enabled clear tumor visualization in PET images. The tumor uptake values of [68Ga]Ga-ProBOMB5, [68Ga]Ga-LW02056, and [68Ga]Ga-LW02057 were 12.4 ± 1.35, 8.93 ± 1.96, and 7.64 ± 0.55%ID/g, respectively, and their average pancreas uptake values were minimal (0.60-1.37%ID/g). Longitudinal SPECT imaging and ex vivo biodistribution studies were also conducted for [177Lu]Lu-ProBOMB5 and clinically validated [177Lu]Lu-RM2. Despite comparable tumor uptake at 1 h post injection ([177Lu]Lu-ProBOMB5:8.09 ± 1.70%ID/g; [177Lu]Lu-RM2:7.73 ± 0.96%ID/g), a faster clearance from PC-3 tumor xenografts was observed for [177Lu]Lu-ProBOMB5, leading to a lower radiation-absorbed dose delivered to tumors. Our data demonstrate that [68Ga]Ga-ProBOMB5 is a promising tracer for clinical translation for detecting GRPR-expressing tumor lesions. However, further optimizations are needed for [177Lu]Lu-ProBOMB5 to prolong tumor retention for therapeutic applications.

The Utility of Baseline Characteristics and [123I]MIBG Cardiac Adrenergic System Scintigraphy in Qualifying Patients with Post-Infarction Heart Failure for Implantable Cardioverter-Defibrillator (ICD) Placement.

Background: Post-infarction heart failure with reduced ejection fraction (HFrEF) patients often face persistent risks of sudden cardiac arrest leading to sudden cardiac death. While implanting a cardioverter-defibrillator (ICD) can enhance prognosis, complications and costs limit its widespread use. Current patient qualification criteria, relying on imperfect parameters, require refinement. The impairment of the cardiac adrenergic system in heart failure is associated with ventricular arrhythmias. The goal of the study was to assess the utility of cardiac adrenergic system scintigraphy in qualifying patients for ICD placement. Methods: In this prospective study of 85 post-infarction HFrEF patients at a single center, clinical assessments, laboratory tests, echocardiography, [123I]MIBG scintigraphy, and ICD implantation were performed. Scintigraphy involved planar chest images and evaluating the heart-to-mediastinum ratio (H/M) and washout rate (WO). SPECT imaging assessed [123I]MIBG uptake in 17 left ventricular segments to calculate the summed difference score (SDS). Results: During a median of 4-year follow-up, 22% of patients experienced appropriate ICD interventions, and 25% of patients died or underwent heart transplantation. The mean values of analyzed parameters did not significantly differ between groups. In the univariate analysis, younger age and moderately impaired left ventricular ejection fraction (LVEF) were correlated with more frequent ICD interventions. In comparison, older age and elevated NT-proBNP levels were associated with death or heart transplantation. Additionally, the univariate analysis identified SDS-15' as a prognostic factor for death/heart transplant. The multivariate analysis identified predictors for ICD interventions, including younger age, an EF of 30% or greater, and a larger left ventricular end-diastolic diameter. In contrast, older age and an LVEF of less than 25% were significant predictors of death or heart transplantation. Conclusions: Scintigraphic parameters did not effectively predict ICD interventions or death/heart transplantation, though the summed difference score demonstrated potential as a prognostic factor. Younger age with moderately impaired EF correlated with frequent ICD interventions, while in older age, EF < 25% predicted death or transplantation. Further investigation is needed for patients with borderline EF values.

Insular monoaminergic deficits in prodromal α-synucleinopathies.

This study assessed data from two cohorts of patients with alpha-synucleinopathies (University of Brescia and University of Rome Tor-Vergata cohorts). Consecutive participants with video-polysomnography-confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and 123I-FP-CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain 123 I-FP-CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls. The cohort (n = 184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age-matched controls. Individuals with iRBD were categorized as RBD-DAT- (n = 32) and RBD-DAT+ (n = 13), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD-DAT- showed an early involvement of the left insula, which increased in RBD-DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR = 3.387; CI 95%: 1.18-10.27]. In this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non-pharmacological interventions.

Comparing Different Methods for the Diagnosis of Liver Steatosis: What Are the Best Diagnostic Tools?

Due to the ongoing organ shortage, marginal grafts with steatosis are more frequently used in liver transplantation, leading to higher occurrences of graft dysfunction. A histological analysis is the gold standard for the quantification of liver steatosis (LS), but has its drawbacks: it is an invasive method that varies from one pathologist to another and is not available in every hospital at the time of organ procurement. This study aimed to compare non-invasive diagnostic tools to a histological analysis for the quantification of liver steatosis. Male C57BL6J mice were fed with a methioninecholine-deficient (MCD) diet for 14 days or 28 days to induce LS, and were compared to a control group of animals fed with a normal diet. The following non-invasive techniques were performed and compared to the histological quantification of liver steatosis: magnetic resonance spectroscopy (MRS), CARS microscopy, 99mTc MIBI SPECT imaging, and a new near-infrared spectrometer (NIR-SG1). After 28 days on the MCD diet, an evaluation of LS showed ≥30% macrovesicular steatosis. High correlations were found between the NIR-SG1 and the blinded pathologist analysis (R2 = 0.945) (p = 0.001), and between the CARS microscopy (R2 = 0.801 (p < 0.001); MRS, R2 = 0.898 (p < 0.001)) and the blinded pathologist analysis. The ROC curve analysis showed that the area under the curve (AUC) was 1 for both the NIR-SG1 and MRS (p = 0.021 and p < 0.001, respectively), while the AUC = 0.910 for the Oil Red O stain (p < 0.001) and the AUC = 0.865 for the CARS microscopy (p < 0.001). The AUC for the 99mTc MIBI SPECT was 0.640 (p = 0.013), and this was a less discriminating technique for LS quantification. The best-performing non-invasive methods for LS quantification are MRS, CARS microscopy, and the NIR-SG1. The NIR-SG1 is particularly appropriate for clinical practice and needs to be validated by clinical studies on liver grafts.

Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas

BackgroundEstimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with 111In-labeled exendin-4 prior to pancreatic resection. In resected pancreas tissue, endocrine-exocrine ratios of tracer uptake were determined by digital autoradiography and accumulation of 111In-labeled exendin-4 was compared to insulin and GLP-1 receptor staining. Of four participants, abdominal single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired to quantify pancreatic uptake in vivoResultsTracer uptake was predominantly present in the endocrine pancreas (endocrine-exocrine ratio: 3.6 [2.8–10.8]. Tracer accumulation showed overlap with insulin-positive regions, which overlapped with GLP-1 receptor positive areas. SPECT imaging showed pancreatic uptake of radiolabelled exendin in three participants.ConclusionRadiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass.Trial registrationClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496. ClinicalTrials.gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508.

Deep-learning-based attenuation map generation in kidney single photon emission computed tomography

BackgroundAccurate attenuation correction (AC) is vital in nuclear medicine, particularly for quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. This study aimed to establish a CT-free quantification technology in kidney SPECT imaging using deep learning to generate synthetic attenuation maps (μ-maps) from SPECT data, thereby reducing radiation exposure and eliminating the need for CT scans.ResultsA dataset of 1000 Tc-99m DTPA SPECT/CT scans was analyzed for training (n = 800), validation (n = 100), and testing (n = 100) using a modified 3D U-Net for deep learning. The study investigated the use of primary emission and scattering SPECT data, normalization methods, loss function optimization, and up-sampling techniques for optimal μ-map generation. The problem of checkerboard artifacts, unique to μ-map generation from SPECT signals, and the effects of iodine contrast media were evaluated. The addition of scattering SPECT to primary emission SPECT imaging, logarithmic maximum normalization, the combination of absolute difference loss (L1) and three times the absolute gradient difference loss (3 × LGDL), and the nearest-neighbor interpolation significantly enhanced AI performance in μ-map generation (p < 0.00001). Checkerboard artifacts were effectively eliminated using the nearest-neighbor interpolation technique. The developed AI algorithm produced μ-maps neutral to the presence of iodine contrast and showed negligible contrast effects on quantitative SPECT measurement, such as glomerular filtration rate (GFR). The potential reduction in radiation exposure by transitioning to AI-based CT-free SPECT imaging ranges from 45.3 to 78.8%.ConclusionThe study successfully developed and optimized a deep learning algorithm for generating synthetic μ-maps in kidney SPECT images, demonstrating the potential to transition from conventional SPECT/CT to CT-free SPECT imaging for GFR measurement. This advancement represents a significant step towards enhancing patient safety and efficiency in nuclear medicine.

The Updated Registry of Fast Myocardial Perfusion Imaging with Next-Generation SPECT (REFINE SPECT 2.0).

The Registry of Fast Myocardial Perfusion Imaging with Next-Generation SPECT (REFINE SPECT) has been expanded to include more patients and CT attenuation correction imaging. We present the design and initial results from the updated registry. Methods: The updated REFINE SPECT is a multicenter, international registry with clinical data and image files. SPECT images were processed by quantitative software and CT images by deep learning software detecting coronary artery calcium (CAC). Patients were followed for major adverse cardiovascular events (MACEs) (death, myocardial infarction, unstable angina, late revascularization). Results: The registry included scans from 45,252 patients from 13 centers (55.9% male, 64.7 ± 11.8 y). Correlating invasive coronary angiography was available for 3,786 (8.4%) patients. CT attenuation correction imaging was available for 13,405 patients. MACEs occurred in 6,514 (14.4%) patients during a median follow-up of 3.6 y (interquartile range, 2.5-4.8 y). Patients with a stress total perfusion deficit of 5% to less than 10% (unadjusted hazard ratio [HR], 2.42; 95% CI, 2.23-2.62) and a stress total perfusion deficit of at least 10% (unadjusted HR, 3.85; 95% CI, 3.56-4.16) were more likely to experience MACEs. Patients with a deep learning CAC score of 101-400 (unadjusted HR, 3.09; 95% CI, 2.57-3.72) and a CAC of more than 400 (unadjusted HR, 5.17; 95% CI, 4.41-6.05) were at increased risk of MACEs. Conclusion: The REFINE SPECT registry contains a comprehensive set of imaging and clinical variables. It will aid in understanding the value of SPECT myocardial perfusion imaging, leverage hybrid imaging, and facilitate validation of new artificial intelligence tools for improving prediction of adverse outcomes incorporating multimodality imaging.

Preclinical Evaluation of 226Ac as a Theranostic Agent: Imaging, Dosimetry, and Therapy.

226Ac (t½ = 29.37 h) has been proposed as a theranostic radioisotope leveraging both its diagnostic γ-emissions and therapeutic α-emissions. 226Ac emits 158 and 230 keV γ-photons ideal for quantitative SPECT imaging and acts as an invivo generator of 4 high-energy α-particles. Because of these nuclear decay properties, 226Ac has potential to act as a standalone theranostic isotope. In this proof-of-concept study, we evaluated a preclinical 226Ac-radiopharmaceutical for its theranostic efficacy and present the first 226Ac-targeted α-therapy study. Methods: 226Ac was produced at TRIUMF and labeled with the chelator-peptide bioconjugate crown-TATE. [226Ac]Ac-crown-TATE was selected to target neuroendocrine tumors in male NRG mice bearing AR42J tumor xenografts for SPECT imaging, biodistribution, and therapy studies. A preclinical SPECT/CT scanner acquired quantitative images reconstructed from both the 158 and the 230 keV emissions. Mice in the biodistribution study were euthanized at 1, 3, 5, 24, and 48 h after injection, and internal radiation dosimetry was derived for the tumor and organs of interest to establish appropriate therapeutic activity levels. Mice in the therapy study were administered 125, 250, or 375 kBq treatments and were monitored for tumor size and body condition. Results: We present quantitative SPECT images of the invivo biodistribution of [226Ac]Ac-crown-TATE, which showed agreement with ex vivo measurements. Biodistribution studies demonstrated high uptake (>30%IA/g at 5 h after injection) and retention in the tumor, with an estimated mean absorbed dose coefficient of 222 mGy/kBq. [226Ac]Ac-crown-TATE treatments significantly extended the median survival from 7 d in the control groups to 16, 24, and 27 d in the 125, 250, and 375 kBq treatment groups, respectively. Survival was prolonged by slowing tumor growth, and no weight loss or toxicities were observed. Conclusion: This study highlights the theranostic potential of 226Ac as a standalone therapeutic isotope in addition to its demonstrated diagnostic capabilities to assess dosimetry in matched 225Ac-radiopharmaceuticals. Future studies will investigate maximum dose and toxicity to further explore the therapeutic potential of 226Ac-radiopharmaceuticals.