Impaired Glymphatic Flow on Diffusion Tensor MRI as a Marker of Neurodegeneration in Alzheimer's Disease: Correlation with Gray Matter Volume Loss and Cognitive Decline Independent of Cerebral Amyloid Deposition.

Background: Impaired glymphatic flow on the Alzheimer's disease (AD) spectrum may be evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Objective: We aimed to validate impaired glymphatic flow and explore its association with gray matter volume, cognitive status, and cerebral amyloid deposition on the AD spectrum. Methods: 80 participants (mean age, 76.9±8.5 years; 57 women) with AD (n = 65) and cognitively normal (CN) (n = 15) who underwent 3T brain MRI including DTI and/or amyloid PET were included. After adjusting for age, sex, apolipoprotein E status, and burden of white matter hyperintensities, the ALPS-index was compared according to the AD spectrum. The association between the ALPS-index and gray matter volume, cognitive status, and quantitative amyloid from PET was assessed. Results: The ALPS-index in the AD was significantly lower (mean, 1.476; 95% CI, 1.395-1.556) than in the CN (1.784;1.615-1.952; p = 0.026). Volumes of the entorhinal cortex, hippocampus, temporal pole, and primary motor cortex showed significant associations with the ALPS-index (all, p < 0.05). There was a positive correlation between the ALPS-index and MMSE score (partial r = 0.435; p < 0.001), but there was no significant correlation between the ALPS-index and amyloid SUVRs (all, p > 0.05). Conclusions: Decreased glymphatic flow measured by DTI-ALPS in AD may serve as a marker of neurodegeneration correlating with structural atrophy and cognitive decline.

Evaluating the Surgical Outcome of Lymphovenous Anastomosis in Breast Cancer-Related Lymphedema Using Tc-99m Phytate Lymphoscintigraphy: Preliminary Results.

Background: Breast cancer-related lymphedema (BCRL) remains a significant postcancer treatment challenge with no definitive cure. Recent supermicrosurgical treatments, such as lymphovenous anastomosis (LVA), have shown promise but lack established objective indicators for outcome evaluation. We investigated the utility of Technetium-99m (Tc-99m) lymphoscintigraphy, an imaging technique providing objective information on lymphatic fluid flow, for assessing LVA surgical outcomes. Methods and Results: A retrospective cohort analysis of patients undergoing LVA for BCRL was conducted. Lymphoscintigraphy images pre- and 1-year postsurgery were compared to determine changes in lymphatic fluid flow of 18 patients based on newly defined parameters "uptake ratio" and "washout rates." Statistically significant reduction in the uptake ratio was observed in the forearm at 30 and 60 minutes postinjection phases. In addition, the forearm showed higher washout rate, indicating an improved lymphatic function in the forearm. Conclusion: Tc-99m lymphoscintigraphy can provide valuable objective data for evaluating LVA surgical outcomes in BCRL patients. However, site-specific differences in outcomes highlight the need for individualized surgical planning. Further large-scale studies are necessary to validate these preliminary findings and develop a standardized approach for LVA assessment.

CT texture features and lung shunt fraction measured using 99mTc-macroaggregated albumin SPECT/CT before trans-arterial radioembolization for hepatocellular carcinoma patients.

The aim of this study is to determine whether contrast-enhanced computed tomography (CECT)-based texture parameters can predict high (> 30 Gy) expected lung dose (ELD) calculated using 99mTc macroaggregated albumin single-photon emission computed tomography/computed tomography (SPECT/CT) for pre-trans-arterial radioembolization (TARE) dosimetry. 35 patients were analyzed, with a treatable planned dose of ≥ 200 Gy for unresectable hepatocellular carcinoma (HCC). Lung shunt fraction (LSF) was obtained from planar and SPECT/CT scans. Texture features of the tumor lesion on CECT before TARE were analyzed. Univariate and multivariate linear regression analyses were performed to determine potential ELD > 30 Gy predictors. Among the 35 patients, nine (25.7%) had ELD > 30 Gy, and had a higher LSF than the ELD ≤ 30 Gy group using the planar (20.7 ± 8.0% vs. 6.3 ± 3.3%; P < 0.001) and SPECT/CT (12.4 ± 5.1% vs. 3.5 ± 2.0%; P < 0.001) scans. The tumor integral total (HU × L) value was a predictor for high LSF using SPECT/CT, with an area under the curve, sensitivity, and specificity of 0.983 (95% confidence interval: 0.869-1.000, P < 0.001), 100%, and 88.5%, respectively. The tumor integral total value is an imaging marker for predicting ELD > 30 Gy. Applying CECT texture analysis may assist in reducing time and cost in patient selection and modifying TARE treatment plans.

Motor subtypes and clinical characteristics in sporadic and genetic Parkinson's disease groups: analysis of the PPMI cohort.

Introduction: The extensive clinical variations observed in Parkinson's disease (PD) pose challenges in early diagnosis and treatment initiation. However, genetic research in PD has significantly transformed the clinical approach to its treatment. Moreover, researchers have adopted a subtyping strategy based on homogeneous clinical symptoms to improve clinical diagnosis and treatment approaches. We conducted a study to explore clinical characteristics in genetic PD groups with motor symptom subtyping. Methods: Data was driven from the Parkinson's Progression Markers Initiative (PPMI) database. The sporadic PD (sPD) group and the genetic PD group including patients with leucine-rich kinase 2 (LRRK2) or glucosylceramidase ß (GBA) mutations were analyzed. Motor subtyping was performed using Movement Disorder Society-Unified Parkinson's disease rating scale (MDS-UPDRS) scores. I-123 FP-CIT SPECT scans were used to calculate specific binding ratios (SBRs) in the caudate and putamen. Clinical symptoms of each group were also compared. Results: MDS-UPDRS III scores were lower in the LRRK2 group, compared with the GBA and sPD group (P < 0.001), but no significant differences in striatal SBRs. The putaminal SBR value of the LRRK2 group was higher than the sPD group (P < 0.05). Within the GBA group, we observed lower SBR values in the postural instability/gait difficulty (PIGD) subtype GBA group compared to the tremor-dominant (TD) subtype GBA group (P < 0.05). The TD subtype GBA group exhibited superior putaminal SBRs compared to the TD subtype sPD group (P < 0.05). The TD subtype LRRK2 group had better putaminal SBR values (P < 0.001) and MDS-UPDRS Part III scores (P < 0.05) compared to the TD sPD group. Discussions: Our subtyping approach offers valuable insights into the clinical characteristics and progression of different genetic PD subtypes. To further validate and expand these findings, future research with larger groups and long-term follow-up data is needed. The subtyping strategy based on motor symptoms holds promise in enhancing the diagnosis and treatment of genetic PD.

Detection of recurrence sites using 18F-fluorocholine PET/CT in prostate cancer patients with PSA failure.

Background: The optimal condition for the clinical application of 18F-fluorocholine positron emission tomography-computed tomography (FCH-PET/CT) to detect recurrence sites in prostate-specific antigen (PSA) failure remains unclear due to the heterogeneity of prostate cancer failure. We aimed to evaluate the detection rate of FCH-PET/CT in prostate cancer patients with PSA failure and to determine the optimal PSA level for performing FCH-PET/CT. Methods: FCH-PET/CT was conducted in 89 patients diagnosed with PSA failure after radical treatment (radical prostatectomy in 75 and definitive radiotherapy in 14) between November 2018 and May 2021. Detection rates were examined via receiver operating characteristic (ROC) analysis, and multivariable logistic regression was performed to identify factors affecting positive FCH-PET/CT findings. We also conducted subgroup analyses according to the PSA failure patterns after the radical treatment (persistently high PSA [N = 48] and biochemical recurrence [BCR] [N = 41]). Results: FCH-PET/CT demonstrated a 59.6% overall detection rate, and the optimal PSA threshold for detecting positive findings was ≥ 1.00 ng/mL at the time of imaging. On multivariable analysis, PSA > 1.00 ng/mL (P < 0.001) was a significant predictor of positive FCH-PET/CT findings, especially regarding distant bone metastases (P < 0.001) and recurrence outside the pelvis (P < 0.001). In a subgroup analysis of patients with BCR after initial radical treatment, the area under the ROC curve (AUC) was 0.82, and PSA ≥ 1.75 ng/mL was the optimal value for identifying positive FCH-PET/CT findings. This PSA value was also associated with significantly higher detection rates of distant bone metastases and outside-pelvis metastasis (P < 0.001, both). Conclusion: FCH-PET/CT is a clinically useful tool for detecting tumor recurrence sites in prostate cancer patients with PSA failure if PSA has exceeded a certain value at the time of imaging. Particularly, higher AUC values were observed when FCH-PET/CT was performed in patients with BCR after initial treatment.

Glymphatic function assessment in Parkinson's disease using diffusion tensor image analysis along the perivascular space.

INTRODUCTION: Glymphatic dysfunction can contribute to α-synucleinopathies. We examined glymphatic function in idiopathic Parkinson's disease (PD) utilizing Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS). METHODS: This study enrolled consecutive patients diagnosed with de novo PD between June 2017 and March 2019 who underwent brain DTI with concurrent 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) SPECT, and age- and sex-matched controls. From DTI-ALPS, the ALPS-index was calculated as a ratio of diffusivities along the x-axis in the region of neural fibers passing vertically to the diffusivities perpendicular to them, which reflected perivascular water motion at the lateral ventricular body level. The ALPS-index of the PD and control groups was compared using Student's t-test; its correlations with clinical scores for motor and cognition (UPDRS-III, MMSE, and MoCA) and striatal dopamine transporter uptake measured by 123I-FP-CIT specific binding ratios (SBRs) were examined using a correlation coefficient. RESULTS: In all, 54 patients in the de novo PD group (31 women, 23 men; mean age, 68.9 ± 9.4 years) and 54 in the control group (mean age, 69.0 ± 10.5 years) were included. The ALPS-index was lower in the PD group than in the controls (1.51 ± 0.22 versus 1.66 ± 0.20; P < 0.001). In the PD group, the ALPS-index negatively correlated with the UPDRS-III score (r = -0.526), and positively correlated with the MMSE (r = 0.377) and MoCA scores (r = 0.382) (all, P < 0.05). No correlation was observed between the ALPS-index and striatal 123I-FP-CIT SBRs (P > 0.05). CONCLUSIONS: DTI-ALPS can reveal glymphatic dysfunction in patients with PD, whose severity correlated with motor and cognitive dysfunction, but not striatal dopamine transporter uptake.

Altered Brain Glymphatic Flow at Diffusion-Tensor MRI in Rapid Eye Movement Sleep Behavior Disorder.

Background Brain glymphatic dysfunction may contribute to the development of α-synucleinopathies. Yet, noninvasive imaging and quantification remain lacking. Purpose To examine glymphatic function of the brain in isolated rapid eye movement sleep behavior disorder (RBD) and its relevance to phenoconversion with use of diffusion-tensor imaging (DTI) analysis along the perivascular space (ALPS). Materials and Methods This prospective study included consecutive participants diagnosed with RBD, age- and sex-matched control participants, and participants with Parkinson disease (PD) who were enrolled and examined between May 2017 and April 2020. All study participants underwent 3.0-T brain MRI including DTI, susceptibility-weighted and susceptibility map-weighted imaging, and/or dopamine transporter imaging using iodine 123-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane SPECT at the time of participation. Phenoconversion status to α-synucleinopathies was unknown at the time of MRI. Participants were regularly followed up and monitored for any signs of α-synucleinopathies. The ALPS index reflecting glymphatic activity was calculated by a ratio of the diffusivities along the x-axis in the projection and association neural fibers to the diffusivities perpendicular to them and compared according to the groups with use of the Kruskal-Wallis and Mann-Whitney U tests. The phenoconversion risk in participants with RBD was evaluated according to the ALPS index with use of a Cox proportional hazards model. Results Twenty participants diagnosed with RBD (12 men; median age, 73 years [IQR, 66-76 years]), 20 control participants, and 20 participants with PD were included. The median ALPS index was lower in the group with RBD versus controls (1.53 vs 1.72; P = .001) but showed no evidence of a difference compared with the group with PD (1.49; P = .68). The conversion risk decreased with an increasing ALPS index (hazard ratio, 0.57 per 0.1 increase in the ALPS index [95% CI: 0.35, 0.93]; P = .03). Conclusion DTI-ALPS in RBD demonstrated a more severe reduction of glymphatic activity in individuals with phenoconversion to α-synucleinopathies. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Filippi and Balestrino in this issue.

Deep learning regressor model based on nigrosome MRI in Parkinson syndrome effectively predicts striatal dopamine transporter-SPECT uptake.

PURPOSE: Nigrosome imaging using susceptibility-weighted imaging (SWI) and dopamine transporter imaging using 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) single-photon emission computerized tomography (SPECT) can evaluate Parkinsonism. Nigral hyperintensity from nigrosome-1 and striatal dopamine transporter uptake are reduced in Parkinsonism; however, quantification is only possible with SPECT. Here, we aimed to develop a deep-learning-based regressor model that can predict striatal 123I-FP-CIT uptake on nigrosome magnetic resonance imaging (MRI) as a biomarker for Parkinsonism. METHODS: Between February 2017 and December 2018, participants who underwent 3 T brain MRI including SWI and 123I-FP-CIT SPECT based on suspected Parkinsonism were included. Two neuroradiologists evaluated the nigral hyperintensity and annotated the centroids of nigrosome-1 structures. We used a convolutional neural network-based regression model to predict striatal specific binding ratios (SBRs) measured via SPECT using the cropped nigrosome images. The correlation between measured and predicted SBRs was evaluated. RESULTS: We included 367 participants (203 women (55.3%); age, 69.0 ± 9.2 [range, 39-88] years). Random data from 293 participants (80%) were used for training. In the test set (74 participants [20%]), the measured and predicted 123I-FP-CIT SBRs were significantly lower with the loss of nigral hyperintensity (2.31 ± 0.85 vs. 2.44 ± 0.90) than with intact nigral hyperintensity (4.16 ± 1.24 vs. 4.21 ± 1.35, P < 0.01). The sorted measured 123I-FP-CIT SBRs and the corresponding predicted values were significantly and positively correlated (ρc = 0.7443; 95% confidence interval, 0.6216-0.8314; P < 0.01). CONCLUSION: A deep learning-based regressor model effectively predicted striatal 123I-FP-CIT SBRs based on nigrosome MRI with high correlation using manually-measured values, enabling nigrosome MRI as a biomarker for nigrostriatal dopaminergic degeneration in Parkinsonism.

Serial Quantitative Assessment of Load Redistribution After Medial Open-Wedge High Tibial Osteotomy.

Background: The maximum standardized uptake value (SUVmax), as determined on combined single-photon emission computed tomography and conventional computed tomography (SPECT/CT), can be an indicator of biomechanical changes due to the load redistribution effect after medial open-wedge high tibial osteotomy (MOW-HTO). Purpose/Hypothesis: The purposes of this study were to (1) analyze serial changes in the SUVmax in the medial, lateral, and patellofemoral compartments after MOW-HTO and (2) identify the contributing factors that affect changes in the SUVmax. The hypotheses were that (1) an elevated SUVmax in the medial compartment would be transferred to the lateral compartment because of the load redistribution effect and (2) there would be contributing factors that cause SUVmax changes. Study Design: Case series; Level of evidence, 4. Methods: Included were 67 knees that were treated with biplanar MOW-HTO between March 2019 and December 2020. SPECT/CT was performed immediately after surgery and at 3 months and 1 year postoperatively to determine the serial load redistribution effect of MOW-HTO. The Pearson correlation coefficient was used to evaluate the relationship between SUVmax and radiological parameters, and subgroup analyses were conducted to compare the SUVmax according to associated cartilage procedures and the weightbearing line ratio (WBLR). Results: The SUVmax in the medial and lateral compartments increased at 3 months but decreased at 1 year postoperatively. The load redistribution effect was most prominent in the anterior zones of the femur (medial: P = .041; lateral: P = .012). In the patella, the SUVmax decreased in both the medial and the lateral zones at all follow-up times (P < .001 for all). The SUVmax in the anterolateral and posterolateral articular zones of the femur increased with a greater preoperative WBLR (r = 0.256, P = .039; and r = 0.261, P = .036, respectively). Patients who underwent an associated cartilage procedure had a significantly higher SUVmax in the anteromedial and posteromedial articular zones of both the femur and the tibia at 1 year postoperatively (P ≤ .002 for all). Conclusion: After MOW-HTO, the unloading effect in the anteromedial articular zone of the femur was the most significant. A greater SUVmax in the lateral zones of the femur was observed in cases of overcorrection. The SUVmax in the medial zones was higher postoperatively in patients with associated cartilage procedures.

Quantitative Iodine-123 single-photon emission computed tomography/computed tomography for Iodine-131 therapy of an autonomously functioning thyroid nodule.

PURPOSE: Autonomously functioning thyroid nodules (AFTNs) are treated with iodine-131 (I-131) therapy, which increases the risk of permanent hypothyroidism; however, the risk can be reduced by separately estimating the accumulated activity for the AFTN and extranodular thyroid tissue (ETT). METHODS: A quantitative I-123 single-photon emission computed tomography (SPECT)/CT (5 mCi) was performed in one patient with unilateral AFTN and T3 thyrotoxicosis. The I-123 concentrations measured at 24 h were 12.26 µCi/mL and 0.11 µCi/mL in the AFTN and contralateral ETT, respectively. Thus, the I-131 concentrations and radioactive iodine uptake expected at 24 h by 5 mCi of I-131 were 38.59 µCi/mL and 0.31 for the AFTN and 0.34 µCi/mL and 0.007 for the contralateral ETT. The weight was calculated as CT-measured volume multiplied by 1.03. RESULTS: In the AFTN patient with thyrotoxicosis, we administered 30 mCi of I-131, which would maximize the 24-h I-131 concentration in the AFTN (226.86 µCi/g) and maintain a tolerable concentration in the ETT (1.97 µCi/g). The percentage of I-131 uptake at 48 h post I-131 administration was 62.6%. The patient achieved a euthyroid state at 14 weeks and maintained the state until 2 years post I-131 administration with an AFTN volume reduction of 61.38%. CONCLUSION: The pre-therapeutic planning of quantitative I-123 SPECT/CT may enable a therapeutic window for I-131 therapy, which directs optimal I-131 activity to effectively treat AFTN while preserving the normal thyroid tissue.

[MRI Findings in Parkinson's Disease: Radiologic Assessment of Nigrostriatal Degeneration]. / 파킨슨병의 ìžê¸°ê³µëª ì˜ìƒ 소견: í‘ì§ˆì„ ì¡°ì²´ 변성의 ì˜ìƒí•™ì  평가.

Parkinson's disease (PD) is a movement disorder that develops due to degenerative loss of dopaminergic cells in the substantia nigra of the midbrain. Recent advances in MRI techniques have demonstrated various imaging findings that can reflect the underlying pathophysiological processes occurring in Parkinson's disease. Many imaging studies have shown that such findings can assist in the diagnosis of Parkinson's disease and its differentiation from atypical parkinsonism. In this review, we present MRI techniques that can be used in clinical assessment, such as nigrosome imaging and neuromelanin imaging, and we provide the detailed imaging features of Parkinson's disease reflecting nigrostriatal degeneration.

Diagnostic accuracy of F-18-Fluorocholine PET/CT and multiparametric MRI for prostate cancer.

Background: Positron emission tomography (PET) using different positron-emitting radiopharmaceuticals has emerged as a promising new metabolic diagnostic tool for the evaluation of a variety of malignant diseases. Thus, we investigated the diagnostic efficacy of F-18-Fluorocholine positron emission tomography/computed tomography (PET/CT) and multiparametric magnetic resonance imaging (mpMRI) for the detection and localization of tumors within the prostate with the correlating histopathology as the standard of reference. Methods: Forty patients with histologically proven prostate cancer underwent both F-18-Fluorocholine PET/CT and mpMRI before robot-assisted laparoscopic radical prostatectomy (RARP). The maximum standard uptake values and the tumor-to-background ratio were measured on a sextant basis. In brief, the sextants were defined as right apex, right middle, right base, left apex, left middle, and left base. For each tumor region, the correlation of the tumor localization based on the sextant in both F-18-Fluorocholine PET/CT and mpMRI scans with the histopathological results was determined. Results: The correlation between both imaging modalities and RARP pathology representing (1) all cancer and (2) clinically significant cancer defined as a ≥ International Society of Urological Pathology grade of 2 showed that the sensitivity and the area under the curve (AUC) were higher for mpMRI than for F-18-Fluorocholine PET/CT. In contrast, F-18-Fluorocholine PET/CT had relatively higher specificity than mpMRI. Importantly, we found a very high AUC value of over 0.8 in both imaging modalities. Conclusion: mpMRI had results superior to F-18-Fluorocholine PET/CT in assessing intraprostatic tumor localization. However, F-18-Fluorocholine PET/CT showed superiority in terms of specificity. Thus, using both modalities in conjunction could provide better treatment planning.

Serial changes of I-123 FP-CIT SPECT binding asymmetry in Parkinson's disease: Analysis of the PPMI data.

Background: Dopaminergic denervation and motor symptoms are usually asymmetric at the onset of Parkinson's disease (PD). In this study, we estimated the asymmetry of specific binding ratio (SBR) of I-123 FP-CIT SPECT images during 4-years of follow up, to demonstrate the pattern of serial changes of asymmetry. Methods: Clinical and I-123 FP-CIT SPECT image data of 301 PD patients and 141 normal controls were reviewed from the Parkinson's Progression Markers Initiative cohort. I-123 FP-CIT SPECT images were taken at baseline, 1-, 2-, and 4-year follow up periods for PD patients, and at baseline for normal controls. Asymmetry index were calculated by two methods. Method 1, by using the ratio of absolute difference of right and left SBRs to the average SBR. Method 2, by using the ratio of absolute difference of right and left SBRs to the SBR values of age-matched normal controls. Results: Asymmetry index by method 2 revealed a more significant decrease during the 4-year follow up period, compared with method 1. The baseline asymmetry index of the putamen by method 2 showed significant correlation with the non-dominant putamen SBRs. However, there were no significant correlation with the baseline asymmetry index by method 2 and motor symptoms, cognition, nor autonomic symptoms. Conclusion: We suggest a novel asymmetry index in association to age-matched normal SBR values. This novel index could be adopted in predicting and evaluating the natural course of PD.

Usefulness of Bone SPECT/CT for Predicting Avascular Necrosis of the Femoral Head in Children with Slipped Capital Femoral Epiphysis or Femoral Neck Fracture.

OBJECTIVE: This study aimed to investigate the usefulness of bone single-positron emission tomography/computed tomography (SPECT/CT) of the hip in predicting the later occurrence of avascular necrosis (AVN) after slipped capital femoral epiphysis (SCFE) or femoral neck fracture in pediatric patients. The quantitative parameters of SPECT/CT useful in predicting AVN were identified. MATERIALS AND METHODS: Twenty-one (male:female, 10:11) consecutive patients aged < 18 years (mean age ± standard deviation [SD], 11.0 ± 2.7 years) who underwent surgery for SCFE or femoral neck fracture and postoperative bone SPECT/CT were included. The maximum standardized uptake value (SUV), mean SUV, and minimum SUV of the femoral head were measured. The ratios of the maximum SUV, mean SUV, and minimum SUV of the affected femoral head to the contralateral side were determined. Patients were followed up for > 1 year after the surgery. The SPECT/CT parameters were compared between patients who developed AVN and those who did not. The accuracy of SPECT/CT parameters for predicting AVN was assessed. RESULTS: Six patients developed AVN. There was a significant difference in the ratio of the mean SUV among patients who developed AVN (mean ± SD, 0.8 ± 0.3) and those who did not (1.1 ± 0.2, p = 0.018). However, there were no significant differences in the ratios of the maximum and minimum SUV between the groups (all p = 0.205). For the maximum, mean, and minimum SUVs, no significant differences were observed between the groups (p = 0.519, 0.733, and 0.470, respectively). The cutoff mean SUV ratio of 0.87 yielded a 66.7% sensitivity and 93.2% specificity for predicting AVN. CONCLUSION: Quantitative bone SPECT/CT is useful for evaluating femoral head viability in pediatric patients with SCFE or femoral neck fractures. Clinicians should consider the high possibility of later AVN development in patients with a decreased mean SUV ratio.

Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice.

[68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [68Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [68Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [68Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions.

Methodological considerations of evaluating the rate of presynaptic dopaminergic denervation in Parkinson disease with radiotracers: Analysis of the PPMI data.

ABSTRACT: Many previous studies have estimated the rate of dopaminergic denervation in Parkinson disease (PD) via imaging studies. However, they lack the considerations of onset age, disease duration at onset, gender, and dopaminergic denervation due to normal aging. Herein, using a large prospective cohort, we estimated the rate of dopaminergic denervation in PD patients, compared with an age- and gender-matched normal control group.One hundred forty-one normal controls and 301 PD patients were enrolled. Striatal specific binding ratios (SBRs) of I-123 FP-CIT single positron emission tomography images were analyzed according to the age of onset, gender, and the duration of motor symptoms.In the PD group, symptom duration was significantly correlated with caudate SBRs, but with putamen SBRs (P  < .05, R2 = 0.02). Moreover, was significantly inversely related to caudate SBRs, but not with putamen SBRs (P  < .05, R2 = 0.02). Patients of different age onsets did not show any significant correlation between symptom durations and striatal SBRs. In the age-matched group, no significant relationship was observed between symptom duration and percent decrease of caudate SBRs, but there was a significant relationship between symptom duration and percent decrease of the putamen SBRs (P  < .01, R2 = 0.06). There was no significant relationship between the symptom duration and the percent decrease of striatal SBRs in the age- and gender-matched group.The significance and R2 values from the regression analysis between symptom duration, age, and dopaminergic denervation are low. This suggests that, contrary to previous knowledge, there is a relatively weak association between dopaminergic denervation and age or symptom duration.

TSPO Expression Modulatory Effect of Acetylcholinesterase Inhibitor in the Ischemic Stroke Rat Model.

We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option.

Imaging the Substantia Nigra in Parkinson Disease and Other Parkinsonian Syndromes.

Parkinson disease is characterized by dopaminergic cell loss in the substantia nigra of the midbrain. There are various imaging markers for Parkinson disease. Recent advances in MRI have enabled elucidation of the underlying pathophysiologic changes in the nigral structure. This has contributed to accurate and early diagnosis and has improved disease progression monitoring. This article aims to review recent developments in nigral imaging for Parkinson disease and other parkinsonian syndromes, including nigrosome imaging, neuromelanin imaging, quantitative iron mapping, and diffusion-tensor imaging. In particular, this article examines nigrosome imaging using 7-T MRI and 3-T susceptibility-weighted imaging. Finally, this article discusses volumetry and its clinical importance related to symptom manifestation. This review will improve understanding of recent advancements in nigral imaging of Parkinson disease. Published under a CC BY 4.0 license.

Patients with scans without evidence of dopaminergic deficit (SWEDD) do not have early Parkinson's disease: Analysis of the PPMI data.

BACKGROUND: To evaluate whether patients with scans without evidence of dopaminergic deficit (SWEDD) have early Parkinson's disease (PD). METHODS: The clinical characteristics, striatal specific binding ratios (SBRs), and the indices of I-123 FP-CIT SPECT images of 50 SWEDD patients, 304 PD patients, and 141 healthy controls were acquired from the Parkinson's Progression Markers Initiative (PPMI) data and evaluated during a 2-year clinical follow-up period. RESULTS: Of the 50 subjects with SWEDD, PD was confirmed in 13 subjects (the PD-SWEDD group), while the remaining 37 subjects had other diseases (the Other-SWEDD group). Striatal SBR values and striatal asymmetry indices of the PD group were significantly different with those of the PD-SWEDD and Other-SWEDD groups at both baseline and after 2 years (p < 0.001). Putaminal SBR values of the PD-SWEDD group were significantly decreased after 2 years (p < 0.05). There was no difference of the SBR values between baseline and after 2 years in the Other-SWEDD group. A baseline MDS-UPDRS III score matched comparison of the PD and PD-SWEDD group was done due to the large difference of the subject numbers. Striatal SBR values and striatal asymmetry indices were significantly different (p < 0.001) between the two groups at both baseline and after 2 years, but there were no significant difference with respect to the MDS-UPDRS III scores after 2 years between the two groups. CONCLUSION: The different SBR values and asymmetry indices between the PD and PD-SWEDD groups at baseline and after 2 years indicate that SWEDD may not be early PD, but rather a different disease entity.