Novel technetium-99m-labeled bivalent PSMA-targeting probe based on hydroxamamide chelate for diagnosis of prostate cancer.

OBJECTIVE: Prostate-specific membrane antigen (PSMA) is a well-known biomarker of prostate cancer. Previously, our group reported that the succinimidyl-cystatin-urea-glutamate (SCUE) moiety has a high affinity for PSMA. In this study, we developed the novel technetium-99m-labeled PSMA-targeting probe "[99mTc]Tc-(Ham-SCUE)2" based on a hydroxamamide chelate with a bivalent SCUE and evaluated its potential as a SPECT imaging probe for the diagnosis of PSMA-expressing prostate cancer. METHODS: Ham-SCUE was synthesized by a one-step reaction with Ham-Mal and cysteine-urea-glutamine. Then, Ham-SCUE was reacted with [99mTc]NaTcO4 for 10 min at room temperature to obtain [99mTc]Tc-(Ham-SCUE)2. [99mTc]Tc-(Ham-SCUE)2 was added to LNCaP (high PSMA expression) cells or PC3 (low PSMA expression) cells, and their radioactivity was measured 60 min after administration. The blocking study was performed by co-incubation of LNCaP cells with various concentrations of 2-PMPA (a PSMA inhibitor) for 15 min before adding [99mTc]Tc-(Ham-SCUE)2. The biodistribution of [99mTc]Tc-(Ham-SCUE)2 in LNCaP/PC3 dual xenografted C.B.-17/Icr scid/scid Jcl mice was evaluated for 120 min after intravenous injection. The blocking study was performed by pretreatment of mice with 2-PMPA (10 mg/kg weight). RESULTS: [99mTc]Tc-(Ham-SCUE)2 was acquired at radiochemical yields of 56% with a radiochemical purity of over 95%. The cellular uptake level of [99mTc]Tc-(Ham-SCUE)2 by LNCaP cells was significantly higher than that by PC3 cells (LNCaP: 11.12 ± 0.71 vs. PC3: 1.40 ± 0.13%uptake/mg protein, p < 0.01), and the uptake was significantly suppressed by pretreatment with 2-PMPA (2.56 ± 0.37%uptake/mg protein, p < 0.05). IC50 of 2-PMPA was 245 ± 47 nM. In the in vivo study, the radioactivity of LNCaP tumor tissue was significantly higher than that of PC3 tumor tissue at 120 min after the administration of [99mTc]Tc-(Ham-SCUE)2 (LNCaP: 9.97 ± 2.79, PC3: 1.16 ± 0.23%ID/g, p < 0.01), and was suppressed by pretreatment with 2-PMPA (2.50 ± 0.45%ID/g, p < 0.01). CONCLUSION: [99mTc]Tc-(Ham-SCUE)2 has the potential to be a SPECT imaging agent for diagnosing high PSMA-expressing prostate cancer.

Odd Sites of Parathyroid Adenomas: 18F-fluorocholine PET/CT Pointing to the Right Place.

Primary hyperparathyroidism is mostly caused by parathyroid adenoma(s) which are generally localized using routine imaging modalities such as neck ultrasonography and 99mTc-SestaMIBI scintigraphy. However, these can miss ectopic parathyroid adenomas due to their limited sensitivities. These ectopic lesions can later lead to failure of surgical excision and necessitate the need for a re-exploration. 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) can help in the localization of these ectopic adenomas due to its superior detection rates and spatial resolution. Herein, we report a case of ectopic parathyroid adenomas that were localized on FCH PET/CT.

Inverse correlation between age of onset and myocardial amyloid deposition quantified by 99mTc-PYP scintigraphy in patients with wild-type transthyretin amyloid cardiomyopathy.

OBJECTIVE: Wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt-CM) is increasingly recognized as a contributing factor to cardiac insufficiency in the elderly population. We aimed to identify the factors affecting age of onset of ATTRwt-CM, encompassing the assessment of amyloid deposition in myocardial tissue through the use of 99mTc-pyrophosphate (PYP) and clinical parameters. METHODS: A retrospective investigation involving a consecutive cohort of 107 cases, each having been diagnosed with ATTRwt-CM confirmed through histopathological and genetic analysis, was performed. All patients underwent PYP scintigraphy, and the heart-to-contralateral (H/CL) ratio was calculated to measure amyloid deposition in the myocardium. Univariate and multivariate analyses were performed to identify independent predictors of the age of onset of ATTRwt-CM, considering the H/CL ratio and various clinical risk factors for heart failure. RESULTS: Gender (p = 0.03), Creatinine (Cr) (r = 0.32, p < 0.01), hemoglobin (Hb) (r = - 0.44, p < 0.01), albumin (Alb) (r = - 0.32, p < 0.01), brain natriuretic peptide (BNP) (r = 0.21, p = 0.03), low-density lipoprotein-cholesterol (LDL-C) (r = - 0.27, p < 0.01), and H/CL ratio (r = - 0.44, p < 0.01) were all significantly associated with the onset age. In multiple regression analysis, the independent predictive factors for the onset age of ATTRwt-CM were identified as the H/CL ratio (p < 0.01), Hb (p < 0.01), and Cr (p < 0.01). CONCLUSION: The H/CL ratio, Hb, and Cr independently affect age of onset in patients with ATTRwt-CM. The H/CL ratio is inversely correlated with age of onset, and may be the sole factor in the development of heart failure in early onset patients, while it may have a synergistic effect on heart failure with anemia and renal dysfunction in late-onset patients.

Self-supervised learning for denoising of multidimensional MRI data.

PURPOSE: To develop a fast denoising framework for high-dimensional MRI data based on a self-supervised learning scheme, which does not require ground truth clean image. THEORY AND METHODS: Quantitative MRI faces limitations in SNR, because the variation of signal amplitude in a large set of images is the key mechanism for quantification. In addition, the complex non-linear signal models make the fitting process vulnerable to noise. To address these issues, we propose a fast deep-learning framework for denoising, which efficiently exploits the redundancy in multidimensional MRI data. A self-supervised model was designed to use only noisy images for training, bypassing the challenge of clean data paucity in clinical practice. For validation, we used two different datasets of simulated magnetization transfer contrast MR fingerprinting (MTC-MRF) dataset and in vivo DWI image dataset to show the generalizability. RESULTS: The proposed method drastically improved denoising performance in the presence of mild-to-severe noise regardless of noise distributions compared to previous methods of the BM3D, tMPPCA, and Patch2self. The improvements were even pronounced in the following quantification results from the denoised images. CONCLUSION: The proposed MD-S2S (Multidimensional-Self2Self) denoising technique could be further applied to various multi-dimensional MRI data and improve the quantification accuracy of tissue parameter maps.

A Review of Advances in Molecular Imaging of Rheumatoid Arthritis: From In Vitro to Clinic Applications Using Radiolabeled Targeting Vectors with Technetium-99m.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder caused by inflammation of cartilaginous diarthrodial joints that destroys joints and cartilage, resulting in synovitis and pannus formation. Timely detection and effective management of RA are pivotal for mitigating inflammatory arthritis consequences, potentially influencing disease progression. Nuclear medicine using radiolabeled targeted vectors presents a promising avenue for RA diagnosis and response to treatment assessment. Radiopharmaceutical such as technetium-99m (99mTc), combined with single photon emission computed tomography (SPECT) combined with CT (SPECT/CT), introduces a more refined diagnostic approach, enhancing accuracy through precise anatomical localization, representing a notable advancement in hybrid molecular imaging for RA evaluation. This comprehensive review discusses existing research, encompassing in vitro, in vivo, and clinical studies to explore the application of 99mTc radiolabeled targeting vectors with SPECT imaging for RA diagnosis. The purpose of this review is to highlight the potential of this strategy to enhance patient outcomes by improving the early detection and management of RA.

The Influence of N-Acetyl-selenomethionine on Two RONS-Generating Cancer Cell Lines Compared to N-Acetyl-methionine.

N-acetyl-selenomethionine (NASeLM), a representative of the selenium compounds, failed to convince in clinical studies and cell cultures that it neither inhibits cancer growth nor has a chemoprotective effect. This study aims to find out whether NASeLM shows a growth-inhibiting property compared to the carrier substance N-Acetyl-L-methionine (NALM) on two different cancer cells, namely Jurkat cells and MTC-SK cells. METHODS: Jurkat and MTC-SK cells were cultured in the absence or presence of varying concentrations (0-500 µg/mL) of NASeLM and NALM solutions. After 0, 24, 48, and 72 h, mitochondrial activity, cancer cell membrane CP levels, cell growth, and caspase-3 activity were assessed in aliquots of Jurkat and MTC-SK cells. RESULTS: Both substances, NASeLM and NALM, were similarly able to inhibit cell growth and mitochondrial activity of Jurkat cells in a concentration-dependent and time-dependent manner up to 70%. Only the determination of caspase activity showed that only NASeLM was able to increase this to almost 40% compared to the control as well as the same lack of NALM. However, the experiments on MTC-SK cells showed a clear difference in favor of NASeLM compared to NALM. While NASeLM was able to reduce cell growth to up to 55%, the same amount of NALM was only at around 15%, which turned out to be highly significant (p < 0.001). The same could also be measured for the reduction in MTC-SK mitochondrial activity. Time dependence could also be recognized: the longer both substances, NASeLM and NALM, were incubated, the higher the effect on cell growth and mitochondrial activity, in favour of NASeLM. Only NASeLM was able to increase caspase-3 activity in MTC-SK cells: at 250 µg/mL NASeLM, caspase-3 activity increased significantly to 28% after 24 and 48 h compared to the control (14%) or the same NALM concentration (14%). After 72 h, this could still increase to 37%. A further increase in the NASeLM concentration did not result in higher caspase-3 activity. CONCLUSION: NASeLM could clearly increase caspase-3 activity in both cell types, Jurkat or MTC-SK cells, and thus induce cell death. NALM and NASeLM showed a reduction in cell growth and mitochondrial activity in both cell lines: While NALM and NASeLM showed almost identical measurements on Jurkat cells, NASeLM was much more effective on MTC-SK than the non-selenium-containing carrier, indicating that it has additional anti-chemoprotective effects.

Management of Petrous Bone Cholesteatoma: The Gruppo Otologico Experience.

BACKGROUND: The term petrous bone cholesteatoma (PBC) refers to lesions extending deep to the bony labyrinth via superior, inferior, and posterior cell tracts. PBC is a rare incidence accounting for only 4-9% of petrous bone lesions. Lesions of petrous bone represent a real surgical challenge due to its complex relationship with critical neurovascular structures. OBJECTIVE: To demonstrate our 40-plus years' experience in the management of PBC, depict the clinical features of PBC according to Sanna's Classification, evaluate the postoperative follow-up of surgically treated PBC patients, and determine the recurrence rate. STUDY DESIGN: Retrospective medical record review. MATERIAL AND METHODS: Medical records of 298 PBC cases operated from the year 1983 to 2024 were thoroughly evaluated. RESULTS: A total of 298 PBC cases were surgically treated at our center. The average age at presentation in this series was 47 years. Males are more affected than females with a male-to-female ratio of 2.2:1. The most common presenting symptoms were hearing loss (84%), tinnitus (48%), and facial nerve paralysis (45%). Mixed hearing loss (41%) was the commonest audiometric pattern of hearing loss followed by conductive hearing loss (26%) and profound sensorineural hearing loss (4%) and a total of 86 (29%) had anacusis at presentation. On preoperative facial nerve function examination, 133(45%) of patients had various degrees of paresis and complete paralysis whereas 55% had normal HB-I function. The commonest degree of paresis noted was HB-III (18%) followed by HB-VI (5%). A total of 150 (50%) patients had previous otologic surgery and two-thirds of these cases had two or more prior otologic surgeries. According to Sanna's PBC Classification system, we identified that the supralabyrinthine class (44%) is the commonest of all classes followed by massive (33%), infralabyrinthine-apical (9%), infralabyrinthine(8%), and apical (5%) classes in that order. However, only ten patients had congenital type of PBC. Extension to clivus, sphenoid, nasopharynx, intradural space, and occipital condyle was found in 8, 2, 1, and 2 cases respectively. The most commonly used surgical approaches at our center were TO, MTCA with rerouting of the facial nerve, and TLAB with external auditory canal (EAC) closure. Postoperative complications were minimal and the duration of follow-up ranged from one to 458 months with a mean duration of 65 months. Residual lesions were evident in 11 cases (3.7%), with the surgical cavity, middle and posterior fossa dura, and jugular bulb being the commonest sites. CONCLUSION: Petrous bone cholesteatoma represents diagnostically and surgically challenging lesions of temporal bone which are usually frustrating to the treating surgeon. A high index of clinical suspicion, thorough clinical evaluation examination, and preoperative radiologic evaluation make the diagnosis easier. Preoperative anatomic classification of the lesion enables the physician to choose the appropriate surgical approach. Sanna's classification is widely used to classify PBC in relation to the labyrinthine block. Radical disease removal should always come before hearing preservation. Cavity obliteration is the solution to the problems related to a large cavity. Finally, advancements in lateral skull base approaches create adequate surgical access for the complete removal of the lesion with excellent control of critical neurovascular structures.

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma: potential therapeutic targets and diagnostic/prognostic markers and web based tools.

This review aimed to describe the inculpation of microRNAs (miRNAs) in thyroid cancer (TC) and its subtypes, mainly medullary thyroid carcinoma (MTC), and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC. Additionally, the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed. This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes, mainly MTC. Additionally, web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described. MiRNAs can perform as oncomiRs or antioncoges, relying on the target mRNAs they regulate. MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases, particularly in cancer. MiRNAs are involved in the modulation of fundamental pathways related to cancer, resembling cell cycle checkpoints and DNA repair pathways. MiRNAs are also rather stable and can reliably be detected in different types of biological materials, rendering them favorable diagnosis and prognosis biomarkers as well. MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets. The contribution of miRNAs in thyroid cancer, particularly MTC, is an active area of research, and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

Role of a novel ER-resident glycoprotein Mtc6/Ehg2 in high-pressure growth: Stability of tryptophan permease Tat2 in Saccharomyces cerevisiae.

Deep-sea organisms are subjected to extreme conditions; therefore, understanding their adaptive strategies is crucial. We utilize Saccharomyces cerevisiae as a model to investigate pressure-dependent protein regulation and piezo-adaptation. Using yeast deletion library analysis, we identified six poorly characterized genes that are crucial for high-pressure growth, forming novel functional modules associated with cell growth. In this study, we aimed to unravel the molecular mechanisms of high-pressure adaptation in S. cerevisiae, focusing on the role of MTC6. MTC6, the gene encoding the novel glycoprotein Mtc6/Ehg2, was found to stabilize tryptophan permease Tat2, ensuring efficient tryptophan uptake and growth under high pressure at 25 MPa. The loss of MTC6 led to promoted vacuolar degradation of Tat2, depending on the Rsp5-Bul1 ubiquitin ligase complex. These findings enhance our understanding of deep-sea adaptations and stress biology, with broad implications for biotechnology, environmental microbiology, and evolutionary insights across species.

Molecular imaging of thyroid and parathyroid diseases.

INTRODUCTION: Molecular imaging of thyroid and parathyroid diseases has changed in recent years due to the introduction of new radiopharmaceuticals and new imaging techniques. Accordingly, we provided an clinicians-oriented overview of such techniques and their indications. AREAS COVERED: A review of the literature was performed in the PubMed, Web of Science, and Scopus without time or language restrictions through the use of one or more fitting search criteria and terms as well as through screening of references in relevant selected papers. Literature up to and including December 2023 was included. Screening of titles/abstracts and removal of duplicates was performed and the full texts of the remaining potentially relevant articles were retrieved and reviewed. EXPERT OPINION: Thyroid and parathyroid scintigraphy remains integral in patients with thyrotoxicosis, thyroid nodules, differentiated thyroid cancer and, respectively, hyperparathyroidism. In the last years positron-emission tomography with different tracers emerged as a more accurate alternative in evaluating indeterminate thyroid nodules [18F-fluorodeoxyglucose (FDG)], differentiated thyroid cancer [124I-iodide, 18F-tetrafluoroborate, 18F-FDG] and hyperparathyroidism [18F-fluorocholine]. Other PET tracers are useful in evaluating relapsing/advanced forms of medullary thyroid cancer (18F-FDOPA) and selecting patients with advanced follicular and medullary thyroid cancers for theranostic treatments (68Ga/177Ga-somatostatin analogues).

Evaluation of Ectopic Kidney Located at the Deep Subcutaneous Region of the Abdominal Wall: Role of Diuretic Renography with 99mTc-DTPA.

An ectopic kidney is often found inadvertently during CT, ultrasonography, MRI, or urologic physical examination. Ectopic kidneys usually occur in the pelvis. A pelvic ectopic kidney may be misinterpreted for a pelvic tumor by less experienced physicians and surgeons. We present an extremely rare case of ectopic kidney in the deep subcutaneous region of the abdominal wall and associated with the additional abnormality of spina bifida. MRI found an ectopic kidney but failed to identify ureteropelvic drainage. Diuretic renography with 99mTc-diethylenetriaminepentaacetic acid showed normal functioning and identified nonobstructive ureteropelvic drainage of the ectopic subcutaneous kidney.

Receptor-Targeted Peptide Conjugates Based on Diphosphines Enable Preparation of 99mTc and 188Re Theranostic Agents for Prostate Cancer.

Benchtop 99Mo/99mTc and 188W/188Re generators enable economical production of molecular theranostic 99mTc and 188Re radiopharmaceuticals, provided that simple, kit-based chemistry exists to radiolabel targeting vectors with these radionuclides. We have previously described a diphosphine platform that efficiently incorporates 99mTc into receptor-targeted peptides. Here, we report its application to label a prostate-specific membrane antigen (PSMA)-targeted peptide with 99mTc and 188Re for diagnostic imaging and systemic radiotherapy of prostate cancer. Methods: Two diphosphine-dipeptide bioconjugates, DP1-PSMAt and DP2-PSMAt, were formulated into kits for radiolabeling with 99mTc and 188Re. The resulting radiotracers were studied in vitro, in prostate cancer cells, and in vivo in mouse xenograft models, to assess similarity of uptake and biodistribution for each 99mTc/188Re pair of agents. Results: Both DP1-PSMAt and DP2-PSMAt could be efficiently radiolabeled with 99mTc and 188Re using kit-based methods to furnish the isostructural compounds M-DP1-PSMAt and M-DP2-PSMAt (M = [99mTc]Tc, [188Re]Re). All 99mTc/188Re radiotracers demonstrated specific uptake in PSMA-expressing prostate cancer cells, with negligible uptake in prostate cancer cells that did not express PSMA or in which PSMA uptake was blocked. M-DP1-PSMAt and M-DP2-PSMAt also exhibited high tumor uptake (18-30 percentage injected dose per gram at 2 h after injection), low retention in nontarget organs, fast blood clearance, and excretion predominantly via a renal pathway. Importantly, each pair of 99mTc/188Re radiotracers showed near-identical biologic behavior in these experiments. Conclusion: We have prepared and developed novel pairs of isostructural PSMA-targeting 99mTc/188Re theranostic agents. These generator-based theranostic agents have potential to provide access to the benefits of PSMA-targeted diagnostic imaging and systemic radiotherapy in health care settings that do not routinely have access to either reactor-produced 177Lu radiopharmaceuticals or PET/CT infrastructure.

Preparation and Evaluation of a Novel 99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent.

Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [99mTc]Tc-CNPN complex with high radiochemical purity (>95%). It was lipophilic and stable in vitro. In HeLa cell experiments, the uptake of [99mTc]Tc-CNPN was effectively inhibited by the ligand CNPN, indicating the binding affinity for PARP. According to the biodistribution studies of HeLa tumor-bearing mice, [99mTc]Tc-CNPN has moderate tumor uptake and can be effectively inhibited, demonstrating its specificity for targeting PARP. The SPECT imaging results showed that [99mTc]Tc-CNPN had tumor uptake at 2 h postinjection. All of the results of this study indicated that [99mTc]Tc-CNPN is a promising tumor imaging agent that targets PARP.

Efficacy and safety of selpercatinib in treating RET-altered MTC: A single-arm meta-analysis.

Background: Selpercatinib is effective in the treatment of RET-altered medullary thyroid carcinoma (MTC). This study aimed to evaluate the efficacy and safety of selpercatinib in the treatment of patients with RET-altered MTC. Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from their inception to April 5, 2024. Outcomes included complete response (CR), partial response (PR), stable disease (SD), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). We carried out a meta-analysis of these studies and exploratory subgroup analyses. The effect sizes for all pooled results were presented as 95% confidence intervals with upper and lower limits. Results: The pooled CR, PR, and SD rates for all patients were 10%, 59%, and 26%, respectively. The pooled ORR in all patients was 70%, while the pooled ORR in pre-treated and non-pre-treated groups were 67% and 70%, respectively. The pooled DCR in all patients was 95%, while the pooled DCR in pre-treated and non-pre-treated groups were 96% and 95%, respectively. The most common AEs associated with selpercatinib were hypertension, alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased. Conclusion: Selpercatinib offers significant benefits to patients with RET-altered MTC with assessable CR, PR, SD, ORR, and grade 3-4 AEs; however, treatment-related AEs should be considered.

Non-contrast preoperative MRI for determining renal perfusion and visualizing renal arteries in potential living kidney donors at 1.5 Tesla.

Background: The aim of this work was to create and evaluate a preoperative non-contrast-enhanced (CE) magnetic resonance imaging (MRI)/angiography (MRA) protocol to assess renal function and visualize renal arteries and any abnormalities in potential living kidney donors. Methods: In total, 28 subjects were examined using scintigraphy to determine renal function. In addition, 3D-pseudocontinuous arterial spin labeling (pCASL), a 2D-non-CE electrocardiogram-triggered radial quiescent interval slice-selective (QISS-MRA), and 4D-CE time-resolved angiography with interleaved stochastic trajectories (CE-MRA) were performed to assess renal perfusion, visualize renal arteries and detect any abnormalities. Two glomerular filtration rates [described by Gates (GFRG) and according to the Chronic Kidney Disease Epidemiology Collaboration formula (GFRCKD-EPI)]. The renal volumes were determined using both MRA techniques. Results: The mean value of regional renal blood flow (rRBF) on the right side was significantly higher than that on the left. The agreements between QISS-MRA and CE-MRA concerning the assessment of absence or presence of an aberrant artery and renal arterial stenosis were perfect. The mean renal volumes measured in the right kidney with QISS-MRA were lower than the corresponding values of CE-MRA. In contrast, the mean renal volumes measured in the left kidney with both MRA techniques were similar. The correlation between the GFRG and rRBF was compared in the same manner as that between GFRCKD-EPI and rRBF. Conclusion: The combination of pCASL and QISS-MRA constitute a reliable preoperative protocol with a total measurement time of <10 min without the potential side effects of gadolinium-based contrast agents or radiation exposure.

Single-center retrospective study of the diagnostic value of double-balloon enteroscopy in Meckel's diverticulum with bleeding.

BACKGROUND: The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel's diverticulum (MD) complicated by digestive tract hemorrhage. Moreover, we aimed to evaluate the value of double-balloon enteroscopy (DBE) in MD diagnosis and the prognosis after laparoscopic diverticula resection. AIM: To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding. METHODS: The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations, auxiliary examination, and follow-up after laparoscopic resection of diverticula. RESULTS: (1) Among 84 MD patients complicated with hemorrhage, 77 were male, and 7 were female with an average age of 31.31 ± 10.75 years. The incidence was higher in men than in women of different ages; (2) Among the 84 MD patients, 65 (78.40%) had defecated dark red stools, and 50 (58.80%) had no accompanying symptoms during bleeding, indicating that most MD bleeding appeared a dark red stool without accompanying symptoms; (3) The shock index of 71 patients (85.20%) was < 1, suggesting that the blood loss of most MD patients was less than 20%-30%, and only a few patients had a blood loss of > 30%; (4) The DBE-positive rate was 100% (54/54), 99mTc-pertechnetate-positive scanning rate was 78% (35/45) compared with capsule endoscopy (36%) and small intestine computed tomography (19%). These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding, especially DBE was a highly precise examination method in MD diagnosis; (5) A total of 54 MD patients with hemorrhage underwent DBE examination before surgery. DBE endoscopy revealed many mucosal manifestations including normal appearance, inflammatory changes, ulcerative changes, diverticulum inversion, and nodular hyperplasia, with ulcerative changes being the most common (53.70%). This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding; and (6) Laparoscopic dissection of diverticulae was performed in 76 patients, The patients who underwent postoperative follow-up did not experience any further bleeding. Additionally, follow-up examination of the 8 cases who had declined surgery revealed that 3 of them experienced a recurrence of digestive tract bleeding. These findings indicate that laparoscopic diverticula resection in MD patients complicated by bleeding had a favorable prognosis. CONCLUSION: Bleeding associated with MD was predominantly observed in male adolescents, particularly at a young age. DBE was a highly precise examination method in MD diagnosis. Laparoscopic diverticula resection effectively prevented MD bleeding and had a good prognosis.

[99mTc]Tc-labeled cyc-DX600-HYNIC as a SPECT probe for ACE2-specific pancreatic cancer imaging.

As a regulator in renin-angiotensin-aldosterone system, angiotensin-converting enzyme 2 (ACE2) closely correlated with tumor progression of pancreatic cancer, meantime, was easily affected by a variety of factors. [99mTc]Tc-cyc-DX600 SPECT was established as an ACE2-specific imaging protocol to figure out the ACE2 status in pancreatic tumor. BALB/C-NU mice were used to prepare the subcutaneous cell derived xenograft (CDX) models with HEK-293T or HEK-293T/hACE2 cells to validate ACE2 specificity of [99mTc]Tc-cyc-DX600 SPECT and establish SPECT imaging protocol. On the basis of [99mTc]Tc-cyc-DX600 SPECT and [18F]F-FDG PET/CT, ACE2-dependence on tumor size and tumor metabolism were further verified on orthotopic pancreatic cancer model with KPC cells. Immunohistochemical analysis was used to demonstrate the findings on ACE2 SPECT. [99mTc]Tc-cyc-DX600 was of superior tumor uptake in HEK-293T/hACE2 CDX than wild type (6.74 ± 0.31 %ID/mL vs 1.83 ± 0.26 %ID/mL at 1.5 h post injection (p.i.); 3.14 ± 0.31 %ID/mL vs 1.16 ± 0.15 %ID/mL at 4.5 h p.i.). For the CDX models with PANC-1 cells, a significant negative correlation between the slope of tumor volume and tumor uptake was observed (r = -0.382 for the 1-4th day; r = -0.146 for the 1-5th day; r = -0.114 for the 1-6th day; r = -0.152 for the 1-7th day; but P > 0.05 for all). For orthotopic pancreatic cancer model, the linear correlation between FDG PET and ACE2 SPECT of the pancreatic lesions was negative (r = -0.878), the quantitative values of ACE2 SPCET was positively correlated with the volume of primary lesions (r = 0.752) and also positively correlated with the quantitative values of ACE2 immunohistochemical analysis (r = 0.991). Conclusively, [99mTc]Tc-cyc-DX600 SPECT is an ACE2-specific imaging protocol with clinical translational potential, adding multidimensional information on the disease progression of pancreatic cancer.

Four-dimensional computed tomography as first-line imaging in primary hyperparathyroidism, a retrospective comparison to conventional imaging in a predominantly single adenoma population.

BACKGROUND: To determine the use of four-dimensional CT as first-line imaging compared to the traditional combination of ultrasound and [99mTc]Tc-Sestamibi SPECT. MATERIALS AND METHODS: Retrospective review of preoperative imaging in patients with primary hyperparathyroidism, who underwent parathyroidectomy between 2012 and 2021. In one group, the combination ultrasound and [99mTc]Tc-Sestamibi SPECT was used as first-line imaging (n = 54), in the other group four-dimensional CT was the first-line imaging modality (n = 51). Sensitivity and positive predictive value were calculated on patient, lateralisation and localisation level. The need for additional imaging was also assessed for both groups. RESULTS: Four-dimensional CT had a significantly higher sensitivity compared to the combination of ultrasound/[99mTc]Tc-Sestamibi SPECT on patient and localisation level (70.6% vs. 51.9%, p = 0.049 and 60.8% vs. 35.2%, p = 0.009 respectively). Sensitivity for lateralisation also appeared higher, but did not reach significance (62.7% vs. 44.4%, p = 0.060). Positive predictive value was not significantly higher for four-dimensional CT compared to ultrasound and [99mTc]Tc-Sestamibi SPECT (88.9% vs. 85.7% for lateralisation and 86.1% vs. 67.9% for localisation respectively). Additional imaging was required in 14 patients with four-dimensional CT as first-line imaging (27.4%) consisting of 2 ultrasound/[99mTc]Tc-Sestamibi SPECT and 13 [18F]fluorocholine PET/CT, compared to 24 patients with ultrasound/[99mTc]Tc-Sestamibi SPECT as first-line imaging (44.4%), requiring 22 four-dimensional CT and 9 [18F]fluorocholine PET/CT. CONCLUSIONS: Four-dimensional CT as the sole first-line parathyroid imaging modality had higher sensitivity than the combination of ultrasound and [99mTc]Tc-Sestamibi SPECT, therefore requiring fewer additional procedures. Although the most costly, [18F]fluorocholine PET/CT was the most effective technique to localise parathyroid adenoma in case all other imaging was negative.