PET radiomics in lung cancer: advances and translational challenges.

Radiomics is an emerging field of medical imaging that aims at improving the accuracy of diagnosis, prognosis, treatment planning and monitoring non-invasively through the automated or semi-automated quantitative analysis of high-dimensional image features. Specifically in the field of nuclear medicine, radiomics utilizes imaging methods such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) to evaluate biomarkers related to metabolism, blood flow, cellular activity and some biological pathways. Lung cancer ranks among the leading causes of cancer-related deaths globally, and radiomics analysis has shown great potential in guiding individualized therapy, assessing treatment response, and predicting clinical outcomes. In this review, we summarize the current state-of-the-art radiomics progress in lung cancer, highlighting the potential benefits and existing limitations of this approach. The radiomics workflow was introduced first including image acquisition, segmentation, feature extraction, and model building. Then the published literatures were described about radiomics-based prediction models for lung cancer diagnosis, differentiation, prognosis and efficacy evaluation. Finally, we discuss current challenges and provide insights into future directions and potential opportunities for integrating radiomics into routine clinical practice.

Physiological provocation compared to acetazolamide in the assessment of cerebral hemodynamics: a case report.

BACKGROUND: Severe large vessel disease may lead to cerebral hemodynamic failure that critically impairs cerebral blood flow (CBF) regulation elevating the risk of ischemic events. Assessment of the condition is often based on changes in CBF during vasodilatation; however, pharmacologically induced vasodilation does not reflect the physiological condition during an ischemic event caused by hemodynamic failure. We compared a [15O]H2O PET brain scan during vasodilation to a [99mTc]HMPAO SPECT brain scan during an ongoing transient ischemic attack (TIA). CASE PRESENTATION: A single patient presenting with limb-shaking TIA underwent CT, Digital Subtraction Angiography, and two different modalities of cerebral perfusion scans: [15O]H2O PET and [99mTc]HMPAO SPECT. Acetazolamide was used in the PET scan to induce vasodilatation, and during the SPECT scan physiological stress, standing up rapidly, was used to induce limb-shaking TIA. CT-angiography and Digital Subtraction Angiography revealed an occlusion in the distal part of the right A2 segment of the anterior cerebral artery, with a corresponding infarction in the watershed area. Collaterals supplied the main vascular territory of the anterior cerebral artery. During rest, neither perfusion modalities demonstrated reduced perfusion outside of the ischemic core. However, we found a pronounced difference between the PET utilizing acetazolamide and the SPECT during the TIA. The PET scan demonstrated relative hypoperfusion in vascular territory supplied by collaterals, while the area around the ischemic core was not affected. Contrary, the SPECT had only minor relative hypoperfusion in the collateral-supplied area, whereas the watershed area proximal to the infarct core had pronounced relative hypoperfusion. CONCLUSIONS: The observed discrepancy in compromised areas during physiological provocation compared to pharmacological induced vasodilation questions the use of an unphysiological stressor for assessment of cerebrovascular hemodynamics. A physiological provocation test may achieve more clinically relevant evaluation.

Cardiac positron emission tomography and other modalities for coronary artery disease assessment: A snapshot from the medicare data.

BACKGROUND: Positron emission tomography (PET) is an important tool for assessing coronary artery disease (CAD), but its widespread utilization is limited due to various factors, including limited local champion availability. This study aims to compare the frequency of PET procedures and their interpreters with other common CAD assessment modalities. METHODS: Using Medicare data, we examined the number of cardiac PET procedures billed and compared them with single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA), stress magnetic resonance imaging (MRI), and stress echocardiography. Healthcare Common Procedure Coding System codes were used to identify procedures. We calculated the total number of PET myocardial perfusion imaging (MPI) procedures, the proportion of PET/CT and myocardial blood flow (MBF) assessments, and the median number of studies read per physician. We also analyzed the trends in the use of different CAD assessment modalities between 2018 and 2022. Descriptive statistics summarized the data. RESULTS: In 2022, Medicare billed for 212,106 PET MPI scans. SPECT was six times more frequent (1,343,519), whereas stress echocardiography (201,676) and CCTA (118,734) had similar or lower use. Stress MRI (3,932) was least used. Of the PET MPI scans, 46% were PET/CT, and 39% included MBF measurements. Cardiologists interpreted 86% of PET scans, with a median of 58 studies per reader; 23% interpreted ≤25 studies annually. SPECT had a median of 63 studies per reader, and CCTA, stress MRI, and stress echocardiography had medians of 27, 20, and 24, respectively. PET, CT, and MRI use increased from 2018 to 2022, whereas SPECT and stress echocardiography declined. CONCLUSION: In the Medicare population, radionuclide perfusion imaging (SPECT and PET) remained the preferred method for assessment of CAD, with SPECT being the most frequently used modality and PET being the second most frequently used modality for this application. However, PET/CT and MBF are underutilized, limiting diagnostic and prognostic capabilities. Efforts to enhance education and awareness of PET's advantages and to address barriers to its wider adoption are essential to maximize its clinical benefits and improve patient outcomes.

Subdiaphragmatic activity-related artifacts in myocardial perfusion scintigraphy.

BACKGROUND: Myocardial perfusion imaging (MPI) with single photon emission computed tomography is an established non-invasive technique for assessing myocardial ischemia. This method involves the intravenous administration of a radiopharmaceutical that accumulates in the heart muscle proportional to regional blood flow. However, image quality and diagnostic accuracy can be compromised by various technical and patient-related factors, including high non-specific radiopharmaceutical uptake in abdominal organs such as the stomach, intestines, liver, and gall-bladder, leading to subdiaphragmatic artifacts. These artifacts are particularly problematic for evaluating inferior wall perfusion and often necessitate repeated imaging, which decreases gamma camera availability and prolongs imaging times. CONCLUSIONS: Despite numerous investigated techniques to reduce interfering gastrointestinal activity, results have been inconsistent, and current MPI guidelines provide scant information on effective procedures to mitigate this issue. Based on our experience, some possible approaches to reducing artifacts include choosing stress testing with an exercise stress test, when possible, late imaging, fluid intake, and consuming carbonated water immediately before imaging.

[Feasibility of Adapting Various Tumor-to-normal Bone Ratio Images on an Automatic Quantification Package for Phantom-based Image Quality Assessment in Bone SPECT].

We investigated the impact of the tumor-to-normal bone ratio (TNR) on the concordance rate between a detectability score classified by software (DSsoft) using an automatic quantification package for bone SPECT (Hone Graph) and a detectability score classified by visual assessment (DSvisual), and considered the feasibility of applying this software to various TNR images. 99mTc solution was filled into a SIM2 bone phantom to achieve TNRs of 4, 6, and 8, performed by dynamic SPECT acquisitions performed for 12 minutes; reconstructions were performed using ordered subset expectation maximization at timepoints ranging from 4 to 12 minutes. This yielded a total of 384 lesions (96 SPECT images). We investigated the weighted kappa (κw) coefficient between DSsoft and DSvisual at various TNRs and evaluated the change in analysis accuracy before and after applying newly created analysis parameters. DSs were defined on a 4-point scale (4: excellent, 3: adequate, 2: average, 1: poor), and visual evaluations were conducted by three board-certified nuclear medicine technologists. The κw coefficients between DSsoft and DSvisual were 0.75, 0.97, and 0.93 for TNRs 4, 6, and 8, respectively, with each κw coefficient being significant (p<0.01). In the TNR 4 image group, κw coefficients significantly increased with the implementation of new parameters proposed in this study. We concluded that the software's automatic analysis would be closer to a visual assessment within the TNR range of 4-8 and that applying new parameters derived from this study to images with TNR 4 further improves the software's automatic analysis accuracy of DSsoft. We suggest that software will be a useful tool for optimizing bone SPECT imaging techniques.

An Analysis of the Diagnostic Performance of Tc-99m PSMA SSPECT/CT in Biochemically Recurrent Prostate Cancer Compared with Ga-68 PSMA PET/CT: A Single-center, Prospective Study.

Objective: Biochemical recurrence (BCR) after initial management of Prostate Carcinoma (PC) is frequent. Subsequent interventions rely on disease burden and metastasis distribution. 68Ga prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is an excellent imaging modality in BCR. However, 68Ga is radionuclide generator produced and has restricted availability. 99mTc-labeled PSMA could be a potential cost-effective alternative. We compared the performance of 99mTc-PSMA single-photon emission CT (SPECT)/CT and 68Ga-PSMA PET/CT in BCR with a serum prostate surface antigen (PSA) level of <20 ng/mL. Materials and Methods: The prospective study included 25 patients with BCR and at least one lesion on a 68Ga-PSMA PET/CT. All patients underwent 99 mTc-PSMA SPECT/CT, and disease distribution and metastatic burden were compared with 68Ga-PSMA PET/CT. The maximum standard uptake value (SUVmax) and the tumor-to-background ratio (TBR) were computed and analyzed. Results: The mean age and serum PSA (SPSA) were 69.72 ± 6.69 years and 5.65 ± 6.07 ng/mL. Eleven patients (44%) had SPSA ≤2 ng/mL. Recurrent sites were noted in the prostate (19, 76%), prostatic bed (3, 12%), and pelvis lymph nodes (LNs) (13, 52%). Distant metastasis to bones (13, 52%), lungs (5, 20%), and retroperitoneal LNs (2, 8%) were noted. Both modalities were concordant for the recurrent disease at the prostate, prostatic bed, bone, and lung lesions. 99mTc-PSMA could localize pelvis LNs in most patients (10/13, 76.9%). The site-specific sensitivity and specificity between the two modalities were not significantly different (P > 0.05). TBR shows excellent correlation with SUVmax (0.783, P < 0.001). Four (16%) patients were understaged with 99mTc-PSMA due to the nonvisualization of the subcentimeter size LNs. No patient with systemic metastases was understaged. Conclusions: 99mTc-PSMA SPECT/CT has good concordance with 68Ga-PSMA PET/CT in BCR, even at low PSA levels. However, it may miss a few subcentimeter LNs due to lower resolution. 99mTc-PSMA SPECT/CT could be a simple, cost-effective, and readily available imaging alternative to PET/CT.

Long-term Side Effect of COVID-19 Infection; Osteonecrosis of the Femoral Head in SPECT/CT Bone Scintigraphy.

Avascular necrosis (AVN) of the femoral head is a condition characterized by limited mobility, discomfort, and changes in walking patterns due to insufficient blood supply in this region. Our objective is to investigate the possible connection between COVID-19 and AVN. In this study, we detail the case of a 41-year-old male patient who developed AVN in both femoral heads after contracting COVID-19. The mere occurrence of a COVID-19 infection and the use of corticosteroids for its treatment may increase the probability of AVN in the femoral head. Hence, post the COVID-19 pandemic, it is crucial to consider AVN vigilantly for timely detection and treatment.

Radiotracers for Molecular Imaging of Angiotensin-Converting Enzyme 2.

Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers.

Advances in CT-based lung function imaging for thoracic radiotherapy.

The objective of this review is to examine the potential benefits and challenges of CT-based lung function imaging in radiotherapy over recent decades. This includes reviewing background information, defining related concepts, classifying and reviewing existing studies, and proposing directions for further investigation. The lung function imaging techniques reviewed herein encompass CT-based methods, specifically utilizing phase-resolved four-dimensional CT (4D-CT) or end-inspiratory and end-expiratory CT scans, to delineate distinct functional regions within the lungs. These methods extract crucial functional parameters, including lung volume and ventilation distribution, pivotal for assessing and characterizing the functional capacity of the lungs. CT-based lung ventilation imaging offers numerous advantages, notably in the realm of thoracic radiotherapy. By utilizing routine CT scans, additional radiation exposure and financial burdens on patients can be avoided. This imaging technique also enables the identification of different functional areas of the lung, which is crucial for minimizing radiation exposure to healthy lung tissue and predicting and detecting lung injury during treatment. In conclusion, CT-based lung function imaging holds significant promise for improving the effectiveness and safety of thoracic radiotherapy. Nevertheless, challenges persist, necessitating further research to address limitations and optimize clinical utilization. Overall, this review highlights the importance of CT-based lung function imaging as a valuable tool in radiotherapy planning and lung injury monitoring.

Case Report: Methylphenidate and venlafaxine improved abdominal nociplastic pain in an adult patient with attention deficit hyperactivity disorder, autism spectrum disorder, and comorbid major depression.

Introduction: Nociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression. Case presentation: Herein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved. Conclusion: The treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP.

Prognostic value of single photon emission computed tomography myocardial perfusion imaging for the prediction of MACE in pre- kidney transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Kidney transplantation provides substantial benefits in extending survival and improving quality of life for patients with end-stage renal disease. The incidence of major adverse cardiac events (MACE) increases with a decline of kidney function in patients with chronic kidney disease. After kidney transplantation, the incidence of MACE remains high. The objective of this study was to assess the prognostic significance of pre-transplant single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in kidney transplant recipients. METHODS: A systematic literature search was performed between January 1st 2015 and March 26th 2024 in PubMed, EMBASE, Web of Science and The Cochrane Library to identify the prognostic value of SPECT MPI for developing MACE (primary outcome) and mortality (secondary outcome) in kidney transplant recipients (PROSPERO CRD42020188610). Risk of bias was assessed. Meta-analyses and subgroup analyses were performed using random-effects models. RESULTS: Six studies comprising 2090 SPECT MPI scans were included. Abnormal SPECT MPI scans were associated with an increased risk of MACE post-transplantation (HR 1.62, 95% CI 1.27-2.06, p < 0.001). Subgroup analyses showed consistent findings across various patient populations and methodological differences. Sensitivity analyses supported the robustness of our findings. CONCLUSIONS: Current evidence showed that pre-transplant SPECT MPI has significant prognostic value in identifying kidney transplant candidates at risk for MACE post-transplantation. Integrating SPECT MPI into preoperative assessments might enhance risk stratification and guide clinical decision-making. Prospective studies are needed to refine risk prediction models.

Evaluation of X-ray protective goggles in mitigating eye lens radiation exposure during radiopharmaceutical handling and patient care in nuclear medicine.

The aim of this study is to estimate eye lens exposure dose when handling radiopharmaceuticals and interacting with patients receiving radiopharmaceuticals, and to verify the usefulness of X-ray protective goggles in mitigating such radiation exposure using phantoms. To evaluate radiation exposure during the handling of radiopharmaceuticals, we employed a fluorescent glass dosimeter to measure the radiation doses associated with 99mTc, 123I, 131I, 111In, and 18F at distances of 30 cm and 60 cm, followed by calculation of the 3 mm dose equivalent rate (3DER). We then estimated the dose reduction rates for various scenarios, including the use of syringe shields and X-ray protective goggles with lead equivalences of 0.07, 0.15, 0.75, and 0.88 mmPb, as well as their combined application. X-ray protective goggles with lead equivalence of 0.75 mmPb outperformed those with 0.07 mmPb and 0.15 mmPb, for all radionuclides and at both source distances. X-ray protective goggles with 0.88 mmPb outperformed those with 0.75 mmPb during handling of 131I and 111In at a distance of 30 cm. In the remaining scenarios, X-ray protective goggles with 0.88 mmPb resulted in marginal reductions or no discernible additional effects. The overall shielding effect of X-ray protective goggles was less pronounced for 131I and 18F, but the combined use of a syringe shield with X-ray protective goggles with 0.75 or 0.88 mmPb improved the dose reduction rate for all scenarios. In simulating patient care, X-ray protective goggles with 0.88 mmPb demonstrated a dose reduction effect of approximately 50% or more. X-ray protective goggles could reduce the 3DER for the eye lens, and were more effective when combined with a syringe shield. It is valid to use a lead equivalence of 0.88 mmPb to fully harness the protective capabilities of X-ray shielding goggles when dealing with all five types of nuclides in clinical settings.

Analysis of bone single-photon emission CT/CT and diffusion-weighted MR imaging in medication-related osteonecrosis of the jaw: focusing on the correlation between standardized uptake values and apparent diffusion coefficient values.

The purpose of this study is to investigate bone SPECT/CT and diffusion-weighted MR imaging (DWI) in medication-related osteonecrosis of the jaw (MRONJ), focusing on the correlation between standardized uptake values (SUVs) and apparent diffusion coefficient (ADC) values. Twenty-nine patients with MRONJ who underwent SPECT/CT and DWI were included in this study. SUVs (maximum and mean) with SPECT/CT, and ADC values (maximum, mean and minimum) with DWI were analyzed on characteristics in MRONJ, such as stage, location, medication and underlying disease, by Mann-Whitney U test. Furthermore, the correlation between SUVs and ADC values for characteristics in MRONJ were assessed by Spearman's rank correlation test for nonparametric data. A p-value lower than 0.05 was considered as statistically significant. SUVs and ADC values have no significant differences for all characteristics in MRONJ. Negative correlations were found in all cases and in stage 2 cases, and no correlations were found in stage 3 cases. In addition, negative correlations were found in maxillary cases, mandibular cases, non-bisphosphonate cases, osteoporosis cases, and malignant tumor cases. In conclusion, this study found multiple correlations between SUVs and ADC values in MRONJ, especially in stage 2. Suggesting that ADC values and SUVs may change with disease progression and the possibility of predicting MRONJ progression by SUVs and ADC values.

The effectiveness of coronary computed tomography angiography and functional testing for the diagnosis of obstructive coronary artery disease: results from the individual patient data Collaborative Meta-Analysis of Cardiac CT (COME-CCT).

AIM: To determine the effectiveness of functional stress testing and computed tomography angiography (CTA) for diagnosis of obstructive coronary artery disease (CAD). METHODS AND RESULTS: Two-thousand nine-hundred twenty symptomatic stable chest pain patients were included in the international Collaborative Meta-Analysis of Cardiac CT consortium to compare CTA with exercise electrocardiography (exercise-ECG) and single-photon emission computed tomography (SPECT) for diagnosis of CAD defined as ≥ 50% diameter stenosis by invasive coronary angiography (ICA) as reference standard. Generalised linear mixed models were used for calculating the diagnostic accuracy of each diagnostic test including non-diagnostic results as dependent variables in a logistic regression model with random intercepts and slopes. Covariates were the reference standard ICA, the type of diagnostic method, and their interactions. CTA showed significantly better diagnostic performance (p < 0.0001) with a sensitivity of 94.6% (95% CI 92.7-96) and a specificity of 76.3% (72.2-80) compared to exercise-ECG with 54.9% (47.9-61.7) and 60.9% (53.4-66.3), SPECT with 72.9% (65-79.6) and 44.9% (36.8-53.4), respectively. The positive predictive value of CTA was ≥ 50% in patients with a clinical pretest probability of 10% or more while this was the case for ECG and SPECT at pretest probabilities of ≥ 40 and 28%. CTA reliably excluded obstructive CAD with a post-test probability of below 15% in patients with a pretest probability of up to 74%. CONCLUSION: In patients with stable chest pain, CTA is more effective than functional testing for the diagnosis as well as for reliable exclusion of obstructive CAD. CTA should become widely adopted in patients with intermediate pretest probability. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Database for Systematic Reviews-CRD42012002780. CRITICAL RELEVANCE STATEMENT: In symptomatic stable chest pain patients, coronary CTA is more effective than functional testing for diagnosis and reliable exclusion of obstructive CAD in intermediate pretest probability of CAD. KEY POINTS: Coronary computed tomography angiography showed significantly better diagnostic performance (p < 0.0001) for diagnosis of coronary artery disease compared to exercise-ECG and SPECT. The positive predictive value of coronary computed tomography angiography was ≥ 50% in patients with a clinical pretest probability of at least 10%, for ECG ≥ 40%, and for SPECT 28%. Coronary computed tomography angiography reliably excluded obstructive coronary artery disease with a post-test probability of below 15% in patients with a pretest probability of up to 74%.

From neurons to brain networks, pharmacodynamics of stimulant medication for ADHD.

Stimulants represent the first line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) and are among the most prescribed psychopharmacological treatments. Their mechanism of action at synaptic level has been extensively studied. However, it is less clear how their mechanism of action determines clinically observed benefits. To help bridge this gap, we provide a comprehensive review of stimulant effects, with an emphasis on nuclear medicine and magnetic resonance imaging (MRI) findings. There is evidence that stimulant-induced modulation of dopamine and norepinephrine neurotransmission optimizes engagement of task-related brain networks, increases perceived saliency, and reduces interference from the default mode network. An acute administration of stimulants may reduce brain alterations observed in untreated individuals in fronto-striato-parieto-cerebellar networks during tasks or at rest. Potential effects of prolonged treatment remain controversial. Overall, neuroimaging has fostered understanding on stimulant mechanism of action. However, studies are often limited by small samples, short or no follow-up, and methodological heterogeneity. Future studies should address age-related and longer-term effects, potential differences among stimulants, and predictors of treatment response.

Involvement of the nigrostriatal system in Gerstman-Sträussler-Scheinker disease with the PRNP-P102L mutation.

INTRODUCTION: Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal-dominant inherited prion disease most often associated with the human prion protein gene (PRNP)-P102L mutation. Although patients manifest considerable phenotypic heterogeneity, the involvement of the nigrostriatal system has not been well-studied. METHODS: We performed dopamine transporter single-photon emission computed tomography (DAT-SPECT) using 123I-ioflupane to investigate the nigrostriatal system function in nine patients with the PRNP-P102L mutation. We also examined the pathological findings in another patient whose predominant feature was ataxia and who died 5 years after disease onset. RESULTS: Striatum uptake of 123I-ioflupane indicated by specific binding ratio (SBR) values was significantly reduced in two patients. The DAT-SPECT examination was performed 6 months after disease onset in one of these patients who manifested rapidly developing cognitive decline mimicking Creutzfeldt-Jakob disease. DAT-SPECT was also performed 9 years after disease onset in another patient who manifested the conventional features of GSS involving ataxia and dementia in the initial phase but showed akinetic mutism at the examination time. Another patient examined 2 years after disease onset who predominantly manifested ataxia showed marginally abnormal SBR values. An autopsy case showed moderate neuronal loss in the substantia nigra, and the degree of neuronal loss was similar in most other parts of the brain. CONCLUSION: Nigrostriatal system involvement may occur in patients with GSS associated with the PRNP-P102L mutation, even though parkinsonism is not the predominant feature.

Phase I Clinical Evaluation of Designed Ankyrin Repeat Protein [99mTc]Tc(CO)3-(HE)3-Ec1 for Visualization of EpCAM-Expressing Lung Cancer.

A high level of EpCAM overexpression in lung cancer makes this protein a promising target for targeted therapy. Radionuclide visualization of EpCAM expression would facilitate the selection of patients potentially benefiting from such treatment. Single-photon computed tomography (SPECT) using 99mTc-labeled engineered scaffold protein DARPin Ec1 has shown its effectiveness in imaging tumors with overexpression of EpCAM in preclinical studies, providing high contrast just a few hours after injection. This first-in-human study aimed to evaluate the safety and distribution of [99mTc]Tc(CO)3-(HE)3-Ec1 in patients with primary lung cancer. Twelve lung cancer patients were injected with 300.7 ± 103.2 MBq of [99mTc]Tc(CO)3-(HE)3-Ec1. Whole-body planar imaging (at 2, 4, 6 and 24 h after injection) and SPECT/CT of the lung (at 2, 4, and 6 h) were performed. The patients' vital signs and possible side effects were monitored up to 7 days after injection. The patients tolerated the injection of [99mTc]Tc(CO)3-(HE)3-Ec1 well, and their somatic condition remained normal during the entire follow-up period. There were no abnormalities in blood and urine tests after injection of [99mTc]Tc(CO)3-(HE)3-Ec1. The highest absorbed doses were in the kidneys, liver, pancreas, thyroid, gallbladder wall, and adrenals. There was also a relatively high accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 in the small and large intestines, pancreas and thyroid. According to the SPECT/CT, accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 in the lung tumor was found in all patients included in the study. Intensive accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 was also noted in regional metastases. [99mTc]Tc(CO)3-(HE)3-Ec1 can potentially be considered a diagnostic tracer for imaging EpCAM expression in lung cancer patients and other tumors with overexpression of EpCAM.

Development of fibroblast activation protein-α radiopharmaceuticals: Recent advances and perspectives.

Fibroblast activation protein-α (FAP) has emerged as a promising target in the field of radiopharmaceuticals due to its selective expression in cancer-associated fibroblasts (CAFs) and other pathological conditions involving fibrosis and inflammation. Recent advancements have focused on developing FAP-specific radioligands for diagnostic imaging and targeted radionuclide therapy. This perspective summarized the latest progress in FAP radiopharmaceutical development, highlighting novel radioligands, preclinical evaluations, and potential clinical applications. Additionally, we analyzed the advantages and existing problems of targeted FAP radiopharmaceuticals, and discussed the key breakthrough directions of this target, so as to improve the development and conversion of FAP-targeted radiopharmaceuticals.

Impact of postoperative cerebral hyperperfusion on 2-year cognitive outcomes of patients undergoing carotid endarterectomy.

OBJECTIVE: In 10% of patients undergoing carotid endarterectomy (CEA), the cognitive function declines postoperatively, primarily in association with postoperative cerebral hyperperfusion. In contrast, in the majority of patients undergoing CEA, long-term cognitive outcomes remain unclear. Furthermore, it is not known whether the decline in cognition due to cerebral hyperperfusion recovers on a long-term basis. This study aimed to understand how postoperative cerebral hyperperfusion affects the cognitive outcomes of patients who undergo CEA. METHODS: The participants in this prospective observational study were patients with internal carotid artery stenosis who underwent CEA. Cerebral hyperperfusion syndrome or asymptomatic cerebral hyperperfusion following CEA was determined based on brain perfusion SPECT scans and symptomatology before and after surgery. Neuropsychological testing was performed preoperatively, at 1-2 months postoperatively, and at 2 years postoperatively to investigate cognitive decline. RESULTS: A logistic regression analysis revealed that asymptomatic cerebral hyperperfusion (95% CI 13.0-84.5, p < 0.0001) and cerebral hyperperfusion syndrome (95% CI 449.7-14,237.4, p < 0.0001) were significantly associated with cognitive decline at 1-2 months postoperatively. The incidence of cognitive decline was significantly decreased at 2 years postoperatively (7%) in comparison to 1-2 months postoperatively (11%) (p = 0.0461). A logistic regression analysis also revealed that asymptomatic cerebral hyperperfusion (95% CI 3.7-36.7, p < 0.0001), cerebral hyperperfusion syndrome (95% CI 128.0-6183.6, p < 0.0001), and further strokes during the 2-year follow-up period (95% CI 1.5-78.7, p = 0.0167) were significantly associated with cognitive decline at 2 years postoperatively. The incidence of cognitive decline at 1-2 months postoperatively was significantly higher in patients with cerebral hyperperfusion syndrome (100%) than in those with asymptomatic cerebral hyperperfusion (44%) (p < 0.0001). No significant difference in incidence was observed in the former patients at 2 years postoperatively (88%), but significant reduction was found in patients with asymptomatic cerebral hyperperfusion and cognitive decline between the timepoints of 1-2 months postoperatively (100%) and 2 years postoperatively (39%) (p = 0.0001). CONCLUSIONS: Postoperative cerebral hyperperfusion causes prolonged cognitive decline at 2 years postoperatively in patients undergoing CEA.

Comparative analysis of peri-nidal cerebral blood flow and metabolism using a novel quantitative 15O-PET method in patients with arteriovenous malformations.

To effectively treat cerebral arteriovenous malformations (AVMs), peri-nidal flow regulation and metabolic status must be understood. In this study, we used 15O-oxygen positron emission tomography (PET) post-processing analysis to investigate vascular radioactivity in the nidal region of AVMs. Single-dynamic PET imaging was performed on seven unruptured AVM patients during the sequential inhalation of 15O2 and C15O2. A previously validated dual-tracer basis function method (DBFM) was employed to calculate parametric images. The results of our study were as follows. First, in remote and contralateral AVM regions, DBFM and a previous approach of dual-tracer autoradiography (DARG) showed strong positive correlations in cerebral blood flow (CBF), cerebral oxygen metabolism rate (CMRO2), and oxygen extraction fraction. Second, peri-nidal CBF and CMRO2 correlation was lower, and overestimation occurred with DARG compared to with DBFM. Third, on comparing DBFM to quantitative 123I-iodoamphetamine single-photon emission computed tomography (SPECT), CBF correlated significantly. In contrast, the correlation between DARG and quantitative 123I-iodoamphetamine-SPECT was weaker in the peri-nidal regions. Fourth, analysis of tissue time-activity curves demonstrated good reproducibility using the novel formulation in the control, peri-nidus, and core nidal regions, indicating the adequacy of this approach. Overall, the DBFM approach holds promise for assessing haemodynamic alterations in patients with AVMs.